Consumer medicine information

Aciclovir-WGR

Aciclovir

BRAND INFORMATION

Brand name

Aciclovir-WGR

Active ingredient

Aciclovir

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Aciclovir-WGR.

SUMMARY CMI

ACICLOVIR-WGR

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 ACICLOVIR-WGR?

This medicine contains the active ingredient aciclovir.

The 200 mg strength is used to:

  • treat genital herpes. It makes an outbreak of genital herpes shorter and less severe;
  • prevent or reduce the number of outbreaks and/or severity of genital herpes in people who experience them often.

The 800 mg strength is used:

  • to treat shingles, also known as herpes zoster. Shingles is caused by the same virus which causes chicken pox. It usually involves nerve pain and a blistery rash, limited to one area of the body. If taken within 72 hours of first getting the rash, aciclovir makes an outbreak of shingles shorter and less severe;
  • as part of the management program for certain infections in people who have the human immunodeficiency virus (HIV). HIV is the virus that causes acquired immune deficiency syndrome (AIDS). Aciclovir does not cure AIDS or get rid of the HIV virus from your body, but it may prevent further damage to the immune system by stopping production of the herpes viruses.

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

2. What should I know before I use ACICLOVIR-WGR?

Do not use if you have ever had an allergic reaction to aciclovir or valaciclovir 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 ACICLOVIR-WGR? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with this medcine 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 ACICLOVIR-WGR?

Your doctor will tell you how much of this medicine you should take. This will depend on your condition and whether you are taking any other medicines.

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

5. What should I know while using ACICLOVIR-WGR?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using this medicine.
  • Make sure you stay well hydrated whilst taking this medicine.
Things you should not doDo not stop taking your medicine or change your dosage without first checking with your doctor.
Driving or using machinesBe careful driving or operating machinery until you know how this medicine affects you.
Looking after your medicine
  • Keep your tablets in the pack until it is time to take them.
  • Keep your medicine in a cool dry place where the temperature stays below 25°C. Protect from light and moisture.
  • Keep it where children cannot reach it.

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

6. Are there any side effects?

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.

Some of the common and serious side effects are included in full below in the CMI. Speak to your doctor if you have any of these serious side effects.

  • symptoms of an allergic reaction such as shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue or other parts of the body; rash, itching or hives on the skin; fainting or hay fever-like symptoms.
  • confusion
  • depression, agitation, irritability
  • unusual thoughts or actions, hallucinations (seeing, feeling or hearing things that are not there)
  • shakiness/trembling
  • difficulty speaking
  • uncoordinated movements, i.e. unsteady walking
  • fever, sore throat, swollen glands
  • blood problems (e.g. feeling tired and weak, fever, frequent infections, unusual bruising or bleeding or swelling around wounds)
  • fluid retention
  • eye problems (inflamed eye).
  • yellowing of the skin and/or eyes (jaundice) or other symptoms indicating liver problems such as: mental confusion, drowsiness, restlessness, itching and unconsciousness
  • kidney problems e.g. too much or too little urine, or pain when urinating, or pain in the kidneys
  • troubled breathing
  • chest pain, fast heart beat (palpitations)
  • convulsion (fits)
  • losing consciousness or in a coma
  • signs of a blood clot such as a swollen and painful area in your leg and swelling in your foot or ankle.

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

ACICLOVIR-WGR

Active ingredient(s): Aciclovir

Consumer Medicine Information (CMI)

This leaflet provides important information about using ACICLOVIR-WGR. 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 this medicine.

Where to find information in this leaflet:

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

1. Why am I using ACICLOVIR-WGR?

This medicine contains the active ingredient aciclovir. Aciclovir belongs to a group of medicines called anti-virals. It works by stopping the production of the virus that causes herpes and shingles. It does not get rid of the virus from your body.

The 200 mg strength is used to:

  • treat genital herpes. It makes an outbreak of genital herpes shorter and less severe;
  • prevent or reduce the number of outbreaks and/or severity of genital herpes in people who experience them often.

The 800 mg strength is used:

  • to treat shingles, also known as herpes zoster. Shingles is caused by the same virus which causes chicken pox. It usually involves nerve pain and a blistery rash, limited to one area of the body. If taken within 72 hours of first getting the rash, aciclovir makes an outbreak of shingles shorter and less severe;
  • as part of the management program for certain infections in people who have the human immunodeficiency virus (HIV). HIV is the virus that causes acquired immune deficiency syndrome (AIDS). Aciclovir does not cure AIDS or get rid of the HIV virus from your body, but it may prevent further damage to the immune system by stopping production of the herpes viruses.

Ask your doctor if you have any questions about why this medicine has been prescribed for you.

Your doctor may have prescribed it for another reason.

This medicine is not addictive.

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

This medicine should not be used in children.

2. What should I know before I use ACICLOVIR-WGR?

Warnings

Do not use this medicine if:

  • you are allergic to aciclovir or valaciclovir, or any of the ingredients listed at the end of this leaflet.

Always check the ingredients to make sure you can use this medicine.

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin
  • fainting or hay fever-like symptoms.

If you think you are having an allergic reaction, do not take any more of the medicine and contact your doctor immediately or go to the Accident and Emergency department at the nearest hospital.

Check with your doctor if you have or have had:

  • kidney or liver problems
  • neurological disorders such as muscle weakness, paralysis, seizures, confusion, etc
  • an imbalance of electrolytes (salts) in your body
  • severe lack of oxygen from any part of your body
  • neurological reactions from a cytotoxic (anti-cancer) medicine.
  • have allergies to any other medicines, foods, preservatives or dyes.

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?

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering.

If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

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.

Your doctor can discuss with you the risks and benefits involved.

If you have not told your doctor about any of the above, tell him/her before you start taking this medicine.

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 may interfere with this medicine and affect how it works. These include:

  • probenecid, a medicine commonly used to treat gout
  • cimetidine, used for stomach problems
  • diuretics, also called fluid tablets
  • interferon, used to treat multiple sclerosis, hepatitis, leukaemia, Hodgkin's lymphoma and other diseases
  • methotrexate given by injection into the spine to treat cancer and leukaemia
  • mycophenolate mofetil, used by people with organ transplants.

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

Other medicines not listed above may also interact with acyclovir.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect this medcine.

4. How do I use ACICLOVIR-WGR?

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

They may differ from the information contained in this leaflet.

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

How much to take

Your doctor will tell you how much of this medicine you should take. This will depend on your condition and whether you are taking any other medicines.

The doses below may be lower if you are elderly or have kidney problems.

Initial genital herpes

The usual dose is one 200 mg tablet every four hours, while awake, for a total of five tablets daily for ten days.

Recurrent genital herpes

The usual dose is one 200 mg tablet three times a day for up to six months.

Or

One 200 mg tablet every four hours, while awake, for a total of five tablets daily for five days.

Shingles

The usual dose is one 800 mg tablet every four hours, while awake, for a total of five tablets daily for seven days (or up to ten days if your eyes are affected by shingles).

Management of HIV

The usual dose is one 800 mg tablet four times a day at six hourly intervals.

When to take this medicine

Take your medicine at about the same time each day.

Taking it at the same time each day will have the best effect. It will also help you remember when to take it.

It does not matter if you take this medicine before or after food.

Continue taking your medicine for as long as your doctor tells you.

Make sure you have enough to last over weekends and holidays.

How to take this medicine

Swallow the tablets whole with a full glass of water.

If you forget to take this medicine

This medicine should be used regularly at the same time each day. If you miss your dose at the usual time:

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Otherwise, take it as soon as you remember, and then go back to taking your medicine as you would normally.

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

This may increase the chance of you getting an unwanted side effect.

If you are not sure what to do, ask your doctor or pharmacist.

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

If you use too much of this medicine

If you think that you have used too much of this medicine, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), 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.

If you take too much of this medicine, you may feel or be sick, have a headache and/or feel confused.

5. What should I know while using ACICLOVIR-WGR?

Things you should do

Remind any doctor, dentist or pharmacist you visit that you are using this medicine.

If you become pregnant while taking this medicine, tell your doctor immediately.

If you are about to have any blood tests, tell your doctor that you are taking this medicine.

It may interfere with the results of some tests.

Make sure you stay well hydrated whilst taking this medicine.

Keep all of your doctor's appointments so that your progress can be checked.

Your doctor may occasionally do tests on your blood or urine to check for side effects and see how your kidneys are working. Go to your doctor regularly for a check-up.

Things you should not do

  • Do not take this medicine to treat any other complaints unless your doctor tells you to.
  • Do not give your medicine to anyone else, even if they have the same condition as you.
  • Do not stop taking your medicine or lower the dosage without checking with your doctor.
  • Do not stop taking your medicine or change your dosage without first checking with your doctor.

Things to be careful of

Genital herpes and HIV can be transmitted to your partner during sexual activity. It is important to remember tha this medicine will not keep you from transmitting herpes or HIV to others.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how this medicine affects you.

This medicine may cause dizziness, tiredness, or drowsiness in some people. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Looking after your medicine

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

If you take the tablets out of the pack, they may not keep well.

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Heat and dampness can destroy some medicines.

Keep it where young children cannot reach it.

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

Getting rid of any unwanted medicine

If your doctor tells you to stop taking this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Less serious side effects

Less serious side effectsWhat to do
  • stomach problems such as nausea (feeling sick), vomiting (being sick), diarrhoea, constipation, stomach pain
  • changes in taste sensation, loss of appetite, weight loss
  • dizziness/giddiness or headache
  • difficulty sleeping
  • increased hair loss
  • weakness, fatigue, lack of energy, tiredness
  • aching, leg pains, muscles pains, joint pain, muscle cramps
  • menstrual problems.
Speak to your doctor or pharmacist if you have any of these less serious side effects and they worry you.
This list includes the more common side effects of this medicine.

Serious side effects

Serious side effectsWhat to do
The following list includes serious side effects that may require medical attention.
  • confusion
  • depression, agitation, irritability
  • unusual thoughts or actions, hallucinations (seeing, feeling or hearing things that are not there)
  • shakiness/trembling
  • difficulty speaking
  • uncoordinated movements, i.e. unsteady walking
  • fever, sore throat, swollen glands
  • blood problems (e.g. feeling tired and weak, fever, frequent infections, unusual bruising or bleeding or swelling around wounds)
  • fluid retention
  • eye problems (inflamed eye).
The following list includes very serious side effects. You may need urgent medical attention or hospitalisation.
  • yellowing of the skin and/or eyes (jaundice) or other symptoms indicating liver problems such as: mental confusion, drowsiness, restlessness, itching and unconsciousness
  • kidney problems e.g. too much or too little urine, or pain when urinating, or pain in the kidneys
  • troubled breathing
  • chest pain, fast heart beat (palpitations)
  • convulsion (fits)
  • losing consciousness or in a coma
  • signs of a blood clot such as a swollen and painful area in your leg and swelling in your foot or ankle.
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.

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 this medicine contains

Active ingredient
(main ingredient)		Aciclovir (200 mg or 800 mg)
Other ingredients
(inactive ingredients)		Magnesium stearate
Microcrystalline cellulose
Sodium starch glycollate
Pre-gelatinised maize starch
Colloidal anhydrous silica.

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

The tablets do not contain any lactose, gluten, tartrazine or any other azo dyes.

What this medicine looks like

200 mg tablets: capsule shaped, biconvex, white to off-white tablets debossed “200” on one side and “ACV” on the other side.

Blister packs of 50 and 90 tablets* (Aust R 431491).

800 mg tablets: capsule shaped, biconvex, white to off-white tablets debossed “800” on one side and “ACV” on the other side.

Blister pack of 35 tablets* (Aust R 431493).

* Not all strengths and/or pack sizes may be available.

Who distributes this medicine

Wagner Pharmaceuticals Pty Ltd
6 Albert Street
Preston VIC 3072
Tel: 1800 936 140

This leaflet was prepared in September 2024.

Published by MIMS December 2024

BRAND INFORMATION

Brand name

Aciclovir-WGR

Active ingredient

Aciclovir

Schedule

S4

 

1 Name of Medicine

Aciclovir.

2 Qualitative and Quantitative Composition

Each tablet contains 200 mg or 800 mg aciclovir.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

200 mg.

Capsule shaped, biconvex, white to off-white tablets debossed "200" on one side and "ACV" on the other side.

800 mg.

Capsule shaped, biconvex, white to off-white tablets debossed "800" on one side and "ACV" on the other side.

4 Clinical Particulars

4.1 Therapeutic Indications

Adults.

Treatment of first episode (primary or nonprimary) genital herpes and the management of recurrent episodes of genital herpes in certain patients.
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 human immunodeficiency virus (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 (HSV) may influence the degree of benefit from therapy.
Intravenous aciclovir should be considered in patients in whom prostration, CNS involvement or inability to take oral medication requires hospitalisation and initiation of more aggressive management.
Aciclovir does not prevent the establishment of latency in initial 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).
Aciclovir 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 Section 5.3 Preclinical Safety Data) 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 aciclovir tablets is being used in the prenatal period (see Section 4.6 Fertility, Pregnancy and Lactation, 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 Section 4.2 Dose and Method of 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 aciclovir 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. Aciclovir tablets appeared to be relatively less effective in younger adults, in whom herpes zoster is generally a milder disease.
In ophthalmic zoster, oral aciclovir 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.

Advanced symptomatic HIV disease.

Studies have shown that oral aciclovir reduced mortality in patients with advanced HIV disease (CD4+ counts < 150 x 106/L). In addition, oral aciclovir provided effective prophylaxis for herpes virus disease. No significant effect was seen on the prophylaxis of cytomegalovirus (CMV) disease or Epstein-Barr virus (EBV) disease.

4.2 Dose and Method of Administration

Aciclovir-WGR tablets may be dispersed in a minimum of 50 mL of water, or swallowed whole with a glass of water.

Treatment of initial genital herpes.

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

Chronic suppressive therapy for recurrent genital herpes.

One 200 mg tablet three times daily for up to six 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 Section 4.1 Therapeutic Indications). Therapy should be discontinued at the end of six 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 Section 4.1 Therapeutic Indications). One 200 mg tablet every four hours while awake, for a total of 5 tablets daily for five 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 five 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 seven days. For herpes zoster ophthalmicus, the recommended duration of therapy is seven to ten 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 aciclovir was given in conjunction with oral 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 four 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 aciclovir 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 twelve 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 eight hours). For patients with creatinine clearance < 10 mL/minute/1.73 m2, 800 mg twice daily (approximately every twelve 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.

4.3 Contraindications

Known hypersensitivity to aciclovir or valaciclovir.

4.4 Special Warnings and Precautions for Use

Use in renal impairment and in the elderly.

Aciclovir is eliminated by renal clearance, therefore the dose must be reduced in patients with renal impairment (see Section 4.2 Dose and Method of 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 Section 4.8 Adverse Effects (Undesirable Effects)). The dosage should be adjusted in patients with renal impairment (see Section 4.2 Dose and Method of Administration).

Hydration status.

Care should be taken to maintain adequate hydration in patients receiving high oral doses of aciclovir.

Other.

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 interferon or intrathecal methotrexate concomitantly.
Animal studies indicate that at high doses aciclovir is cytotoxic.

Use in the elderly.

See Use in renal impairment and in the elderly.

Paediatric use.

Safety and effectiveness in children have not been established.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of 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 aciclovir, 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 coadministrated. 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 zidovudine no significant overall increase in toxicity was associated with the addition of aciclovir. No data are available on interactions between aciclovir and other antiretroviral therapies.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There is no experience of the effect of aciclovir 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.
(Category B3)
Animal studies show that aciclovir crosses the placenta readily. Aciclovir was not teratogenic in the mouse (450 mg/kg/day orally), rabbit (50 mg/kg/day subcutaneously and intravenously) or rat (50 mg/kg/day subcutaneously) 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 four hours. In additional studies in which rats were given three subcutaneous doses of aciclovir 100 mg/kg on gestation day 10, fetal abnormalities, e.g. 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.
 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 acyclovir is to be administered to a nursing woman.

4.7 Effects on Ability to Drive and Use Machines

The clinical status of the patient and the adverse event profile of aciclovir 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 acyclovir 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.

4.8 Adverse Effects (Undesirable Effects)

Aciclovir 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 zidovudine), no significant overall increase in toxicity was associated with the addition of aciclovir. 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.

Hepato-biliary 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.

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 http://www.tga.gov.au/reporting-problems.

4.9 Overdose

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.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Microbiology.

Aciclovir is an antiviral agent which is active in vitro against 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.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

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 every four hours 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 peak 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 of 200 mg aciclovir as Aciclovir-WGR 200 mg, the mean plasma half-life of aciclovir in volunteers with normal renal function was 3.4 hours. For volunteers dosed with 800 mg aciclovir as Aciclovir-WGR 800 mg, the mean plasma half-life was 7.2 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-carboxymethoxymethyl guanine is the major metabolite of aciclovir and accounts for 10-15% of the dose excreted in the urine following intravenous administration.
In children aged 0 to 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 intravenous administration was found to be 19.5 ± 5.9 (standard deviation) 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 aciclovir tablets is recommended in renal impairment (see Section 4.2 Dose and Method of Administration).
Plasma protein binding is low (9-33%).

5.3 Preclinical Safety Data

Genotoxicity.

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 four microbial assays. Positive results were obtained in two of seven genetic toxicity assays using mammalian cells in vitro (positive in human lymphocytes in vitro and one locus in mouse lymphoma cells, negative at two other loci in mouse lymphoma cells, and three 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 humans at therapeutic dose levels.

Carcinogenicity.

Aciclovir was positive in one of two mouse cell transformation systems in vitro. Inoculation of the transformed cells into immunosuppressed 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 tumorigenicity but in these species the absorption of oral aciclovir is poor and possibly self-limiting.

6 Pharmaceutical Particulars

6.1 List of Excipients

Magnesium stearate, microcrystalline cellulose, sodium starch glycollate, pregelatinised maize starch, colloidal anhydrous silica.

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. Protect from light and moisture.

6.5 Nature and Contents of Container

200 mg tablets are available in blister packs of 50s and 90s.
800 mg tablets are available in blister packs of 35s.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.


Chemical name: 2-amino-9-[(2-hydroxyethoxy) methyl]-1,9-dihydro- 6H-purin-6-one.
Synthetic acyclic purine nucleoside analogue. It is a white or almost white crystalline powder, slightly soluble in water, very slightly soluble in ethanol (96 per cent), practically insoluble in heptane. It dissolves in dilute solutions of mineral acids and alkali hydroxides.

CAS number.

59277-89-3.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes