Consumer medicine information

Aciclovir Sandoz® IV Infusion

Aciclovir

BRAND INFORMATION

Brand name

Aciclovir Sandoz IV Infusion (Powder for infusion)

Active ingredient

Aciclovir

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Aciclovir Sandoz® IV Infusion.

WHAT IS IN THIS LEAFLET

This leaflet answers some common questions about Aciclovir Sandoz IV Infusion.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of giving you Aciclovir Sandoz IV Infusion against the benefits it is expected to have for you.

If you have any concerns about this medicine, ask your doctor or pharmacist.

Keep this leaflet after your hospital stay.

You may need to read it again.

WHAT ACICLOVIR SANDOZ IV INFUSION IS USED FOR

Aciclovir Sandoz IV Infusion belongs to a group of medicines called antivirals.

It is used for the treatment of a number of different conditions caused by viruses, such as shingles and herpes, especially in patients who have reduced immunity.

Aciclovir Sandoz IV Infusion works by preventing the multiplication of the virus which is causing the condition.

Your doctor may have prescribed Aciclovir Sandoz IV Infusion for another reason. Ask your doctor if you have any questions about why this medicine has been prescribed for you.

This medicine is available only with a doctor’s prescription. It should only be given to you under the supervision of medical professionals.

Aciclovir Sandoz IV Infusion is not addictive.

BEFORE YOU ARE GIVEN ACICLOVIR SANDOZ IV INFUSION

When you must not use it

Do not use this medicine if you have an allergy to:

  • aciclovir, or to any of the other ingredients listed at the end of this leaflet under Product Description
  • valaciclovir.

Symptoms of an allergic reaction may include asthma, wheezing or shortness of breath, swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing, hives, itching or skin rash or fainting.

If you are not sure whether you should be given Aciclovir Sandoz IV Infusion, talk to your doctor, nurse or pharmacist.

Aciclovir Sandoz IV Infusion should not be given to children younger than twelve months of age.

The safety and effectiveness of Aciclovir Sandoz IV Infusion in children less than twelve months of age have not been established.

Before you are given it

Tell your doctor if:

  1. you are pregnant, or intend to become pregnant.
    Like most medicines, Aciclovir Sandoz IV Infusion is not recommended for use during pregnancy. Your doctor will discuss the possible risks and benefits of using Aciclovir Sandoz IV Infusion during pregnancy.
  2. you are breast-feeding or intend to breast-feed.
    Aciclovir Sandoz IV Infusion passes into breast milk and therefore there is a possibility that the breast-fed baby may be affected. Aciclovir Sandoz IV Infusion is not recommended for use while breast-feeding. Your doctor will discuss the risks and benefits of using Aciclovir Sandoz IV Infusion when breast-feeding.
  3. you have or have had any other health problems including:
  • any condition affecting your nervous system
  • hypoxia
  • liver or kidney problems
  • irregular electrolyte levels
  • dehydration
  • low blood pressure.
  1. you are allergic to any other medicines, foods, dyes or preservatives.

If you have not told your doctor about any of the above, tell them before you are given Aciclovir Sandoz IV Infusion.

Using other medicines

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

Some medicines may interfere with Aciclovir Sandoz IV Infusion. These include:

  • probenecid, a medicine used to treat gout
  • cimetidine, a medicine used to treat ulcers
  • mycophenolate mofetil, cyclosporin or tacrolimus
  • diuretics or fluid tablets
  • interferon
  • methotrexate.

These medicines may be affected by Aciclovir Sandoz IV Infusion or may affect how well Aciclovir Sandoz IV Infusion works. You may need different amounts of your medicines or you may need to take different medicines. Your doctor or pharmacist can tell you what to do if you are using any of these medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while using Aciclovir Sandoz IV Infusion.

HOW ACICLOVIR SANDOZ IV INFUSION IS GIVEN

Aciclovir Sandoz IV Infusion should only be given to you by a trained medical professional.

Aciclovir Sandoz IV Infusion is given by infusion into a vein over a period for at least an hour. It is not to be given by mouth.

The amount you will be given will be specific to your age, weight, general health and underlying conditions.

The duration of treatment is dependent on the condition that is being treated.

If you have been given too much (overdose)

Your prescribing doctor has information on how to recognise and treat an overdose.

If you are given too much Aciclovir Sandoz IV Infusion, you may experience symptoms such as nausea, vomiting, stomach pain, confusion, agitation, drowsiness, hallucinations, tremors or convulsions.

You will be closely monitored whilst you are being treated with this medicine. Should any symptoms of an overdose occur your doctor would manage them.

WHILE YOU ARE RECEIVING ACICLOVIR SANDOZ IV INFUSION

Things you must do

If the symptoms of your illness do not improve within a few days, or if they become worse, tell your doctor or nurse.

Drink plenty of fluids.

If you cannot drink, your doctor will ensure that you receive plenty of fluids.

Tell your doctor immediately if you become pregnant while you are using Aciclovir Sandoz IV Infusion.

If you are about to start taking any new medicine, tell your doctor and pharmacist that you are using Aciclovir Sandoz IV Infusion.

Things be careful of

Be careful driving or operating machinery until you know how Aciclovir Sandoz IV Infusion affects you.

SIDE EFFECTS

Tell your doctor, nurse or pharmacist as soon as possible if you do not feel well after you have received Aciclovir Sandoz IV Infusion.

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

Tell your doctor or nurse if you notice any of the following and they worry you:

  • pain and swelling at the injection site
  • nausea (feeling sick) or vomiting
  • skin rash, increased sensitivity of the skin to the sun or itchiness.

These side effects are usually mild.

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

Tell your doctor or nurse immediately or, if you have already left hospital, go to the Accident and Emergency at your nearest hospital if you notice any of the following:

  • headache, light-headedness or dizziness especially if you get up suddenly from a lying or sitting position
  • extreme or unusual tiredness, drowsiness, unsteadiness when walking or shaking
  • confusion, agitation, hallucinations or convulsions
  • fever
  • yellowing of the eyes or skin, also called jaundice
  • lumpy rash (hives)
  • wheezing, shortness of breath or difficulty breathing
  • swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing
  • bleeding or bruising more easily than normal
  • reduced or loss of sensation, especially in the hands or feet
  • diarrhoea or stomach pain
  • discoloured or blood in the urine
  • sweating
  • passing less urine than is normal for you.

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

Other side effects not listed above may also occur in some patients. Tell your doctor if you notice anything that is making you feel unwell.

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

PRODUCT DESCRIPTION

What it looks like

Aciclovir Sandoz IV Infusion is supplied in colourless glass vial containing a white or almost white crystalline powder.

Aciclovir Sandoz IV Infusion comes in packs of 5’s.

Aciclovir Sandoz IV Infusion is intended for single patient use only. Any remaining content should be discarded.

Storage

Aciclovir Sandoz IV Infusion will be stored in the pharmacy or on the ward. It is kept in a cool dry place where the temperature stays below 25ºC. It should be protected from moisture.

Ingredients

Active ingredient:

  • Aciclovir 250 mg or 500 mg as aciclovir sodium

Inactive ingredient:

  • Residual quantities of sodium hydroxide used to form aciclovir sodium salt

The product does not contain any preservative.

Supplier

Sandoz Pty Ltd
ABN 60 075 449 553
19 Harris St
Pyrmont NSW 2009
Australia
Tel: 1800 634 500

This leaflet was revised in June 2012.

Australian Register Numbers
250 mg powder for injection AUST R 75839
500 mg powder for injectionAUST R 75838

BRAND INFORMATION

Brand name

Aciclovir Sandoz IV Infusion (Powder for infusion)

Active ingredient

Aciclovir

Schedule

S4

 

Name of the medicine

Aciclovir.

Excipients

Sodium hydroxide (residual amount).

Description

Chemical name: 9-[(2-hydroxyethoxy)methyl]guanine. Molecular formula: C8H11N5O3. MW: 225.2. CAS: 59277-89-3. Aciclovir is a white or almost white, crystalline powder, slightly soluble in water, freely soluble in dimethyl sulfoxide, very slightly soluble in alcohol. It dissolves in dilute solutions of mineral acids and alkali hydroxides. Soluble in 1 in 10 of water.

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. However, the relationship between 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.

The terminal plasma half-life of aciclovir in adults with normal renal function is approximately three hours. Approximately 60% of the medicine is excreted unchanged by the kidney by glomerular filtration and tubular excretion. When aciclovir is given one hour after probenecid 1 g the terminal half-life and the area under the plasma concentration time curve are extended by 18 and 40%, respectively.
9-Carboxymethoxymethylguanine is the major metabolite of aciclovir and accounts for 10 to 15% of the dose excreted in the urine following IV administration.
Mean steady state peak plasma concentrations (Cssmax) following a one hour infusion of aciclovir 5 or 10 mg/kg were about 9.8 and 20.7 mg/mL, respectively. The trough plasma concentrations (Cssmin) were about 0.7 and 2.0 mg/mL, respectively. In children over 1 year of age similar mean peak (Cssmax) and trough (Cssmin) levels were observed when a dose of 250 mg/m2 was substituted for 5 mg/kg and a dose of 500 mg/m2 was substituted for 10 mg/kg. In children aged 0 to 3 months the terminal plasma half-life is approximately four hours. However, experience is insufficient at present to recommend therapy for this age group.
In patients with chronic renal failure the mean terminal half-life following intravenous administration was found to be approximately 20 hours. The mean aciclovir half-life during haemodialysis was 5.7 hours. Plasma aciclovir levels dropped approximately 60% during dialysis. Plasma protein binding is low (9 to 33%).

Indications

Aciclovir Sandoz I.V. infusion is indicated for promoting resolution of acute clinical manifestations of mucocutaneous herpes simplex infections in immunocompromised patients.
Treatment of severe first episode primary or nonprimary genital herpes in immune competent patients.
Treatment of acute manifestations of varicella voster virus infection in immunocompromised patients.
Treatment of herpes zoster (shingles) in immune competent patients who show very severe acute local or systemic manifestations of the disease. (Benefits can be expected in patients with rash duration shorter than 72 hours. The use of the intravenous infusion may be warranted in only a small subgroup of immune competent patients with shingles.)
Treatment of herpes simplex encephalitis.

Contraindications

Aciclovir IV infusion powder for reconstitution is contraindicated in patients known to be hypersensitive to aciclovir or valaciclovir.

Precautions

Aciclovir intravenous infusion is intended for intravenoususe only and should not be administered by any other route. Extravascular infusion can cause a severe local inflammation, possibly with tissue necrosis, because the infusion fluid has a pH of 10 to 11. The product should not be administered orally. Contact with the eyes and the unprotected skin must be avoided.
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 medicines or who are receiving concomitantly interferon or intrathecal methotrexate. Animal studies indicate that at high doses aciclovir is cytotoxic.
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 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. Prolonged or repeated courses of aciclovir in severely immunocompromised individuals may result in the selection of virus strains with reduced sensitivity, which may not respond to continued aciclovir treatment. The relationship between in vitro sensitivity of herpes viruses to aciclovir and clinical response to therapy has yet to be established.

Warnings.

Impaired renal function.

In patients with impaired renal function the dosage must be adjusted in order to avoid accumulation of aciclovir in the body. For patients who are treated with high doses of aciclovir intravenous infusion, e.g. because of herpes encephalitis, special attention must be paid to the renal function, particularly in patients who are dehydrated or who have impaired renal function.
Aciclovir is eliminated by renal clearance. Therefore the dose must be reduced in patients with renal impairment. 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).
Aciclovir intravenous infusion must be given over a period of at least one hour in order to avoid renal tubular damage. It should not be administered as a bolus injection. Although the aqueous solubility of aciclovir sodium (for infusion) exceeds 100 mg/mL, precipitation of aciclovir crystals in renal tubules, and the consequent renal tubular damage, can occur if the maximum solubility of free aciclovir (2.5 mg/mL at 37°C in water) is exceeded.
Aciclovir intravenous infusion must be accompanied by adequate hydration. Since maximum urine concentration occurs within the first few hours following infusion, particular attention should be given to establish sufficient urine flow during that period. Concomitant use of other nephrotoxic medicines, pre-existing renal disease and dehydration increase the risk of further renal impairment by aciclovir infusion.

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 orally (PO)), rabbit (50 mg/kg/day subcutaneously (SC) and intravenously (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 similar to the mean steady-state peak concentration in humans after one hour infusions of 10 mg/kg every eight hours. In additional studies in which rats were given aciclovir 100 mg/kg three SC doses on gestation day 10, fetal abnormalities, such as head and tail anomalies, were reported (exposure was fivefold human levels after 10 mg/kg infusions).
There have been no adequate and well controlled studies concerning the safety of aciclovir in pregnant women. Aciclovir should not be used during pregnancy unless the potential benefit to the patient justifies the potential risk to the foetus. 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.

Paediatric use.

Adjustment of dosage is required for administration to children (see Dosage and Administration).

Patients with impaired renal function.

Both in adults as well as in children the daily dose must be reduced by increasing the dosing intervals (see Dosage and Administration). Furthermore, a new dose must be administered to patients who are undergoing haemodialysis after every haemodialysis.

Mutagenicity.

Aciclovir was clastogenic in Chinese hamster cells in vivo, at exposure levels also causing nephrotoxicity (500 and 100 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 result of these mutagenicity tests in vitro and in vivo suggests 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 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 tumorogenicity but in these species the absorption of oral aciclovir is poor and possibly self limiting.

Effects on fertility.

There is no experience of the effect of aciclovir on human fertility. The results of studies in animals indicate that aciclovir should have no effect on fertility in humans at therapeutic doses.

Interactions

Aciclovir is eliminated primarily unchanged in the urine via renal tubular secretion. Any medicines administered concurrently that compete with this mechanism or affect renal physiology may increase aciclovir plasma concentration. Probenecid and cimetidine increase the AUC of aciclovir by this mechanism and reduce aciclovir renal clearance.
In patients receiving intravenousaciclovir, caution is required during concurrent administration with medicines which compete with aciclovir for elimination, because of the potential for increased plasma levels of one or both medicines or their metabolites. Increases in plasma AUCs of aciclovir and of the inactive metabolite of mycophenolate mofetil, an immunosuppressant agent used in transplant patients, have been shown when the medicines are coadministered.
Care is also required (with monitoring for changes in renal function) if administering intravenousaciclovir with medicines which affect other aspects of renal physiology (e.g. cyclosporin, tacrolimus).
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. Aciclovir should also be used with caution in patients who have manifested neurological reactions to cytotoxic drugs or are receiving concomitantly interferon or intrathecal methotrexate (See Precautions).

Adverse Effects

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 ≥ 1/1,000 and < 1/100; rare ≥ 1/10,000 and < 1/1,000; very rare < 1/10,000.

Blood and lymphatic system disorders.

Uncommon: decreases in haematological indices (anaemia, thrombocytopenia, leucopenia).

Immune system disorders.

Very rare: anaphylaxis.

Psychiatric and nervous system disorders.

Common: lethargy, obtundation, tremors, confusion, hallucinations, agitation, somnolence, psychosis, convulsions and coma. Very rare: headache, dizziness, ataxia, dysarthria, encephalopathy.
The above reversible events are usually seen in medically complicated cases.

Vascular disorders.

Common: phlebitis.

Respiratory, thoracic and mediastinal disorders.

Very rare: dyspnoea.

Gastrointestinal disorders.

Common: nausea, vomiting. Very rare: diarrhoea, abdominal pain.

Hepatobiliary disorders.

Common: reversible increases in liver related enzymes. Very rare: reversible increases in bilirubin, jaundice, hepatitis.

Skin and subcutaneous tissue disorders.

Common: pruritus, urticaria, rashes (including photosensitivity). Very rare: angioedema.

Renal and urinary disorders.

Common: increases in blood urea and creatinine.
Rapid increases in blood urea and creatinine levels are believed to be related to the peak plasma levels and the state of hydration of the patient. To avoid this effect the drug should not be given as an intravenous bolus injection but by slow infusion over a one hour period.
Very rare: renal impairment, acute renal failure.
Adequate hydration should be maintained. Renal impairment usually responds rapidly to rehydration of the patient and/or dosage reduction or withdrawal of the drug. Progression to acute renal failure, however, can occur in exceptional cases.
Renal pain may be associated with renal failure.

Liver.

Very rare: hepatitis and jaundice.

General disorders and administration site conditions.

Very rare: fatigue, fever, local inflammatory reactions.
Severe local inflammatory reactions sometimes leading to breakdown of the skin have occurred when aciclovir infusion has been inadvertently infused into extracellular tissues.

Others.

Uncommon: diaphoresis, haematuria, hypotension and headache.

Dosage and Administration

See Indications. (See Table 1.)
Each dose should be administered by slow intravenous infusion over a one hour period.

Patients with impaired renal function.

Both in adults as well as in children the daily dose must be reduced by increasing the dosing intervals (see Table 2).

Dosage in children.

The dosage of aciclovir intravenous infusion in children aged 1 to 12 years should be calculated on the basis of the body surface area.
Children in this age group with herpes simplex infections (except herpes simplex encephalitis) or varicella zoster infections should be given Aciclovir Sandoz infusion in doses of 250 mg/m2 of body surface area (equivalent to 5 mg/kg in adults).
Immunocompromised children in this age group with varicella zoster virus infections or with herpes simplex encephalitis should be given Aciclovir Sandoz infusion in doses of 500 mg/m2 of body surface area (equivalent to 10 mg/kg in adults).
Children with impaired renal function require an appropriately modified dose, according to the degree of impairment.

Dosage in the elderly.

No data are available in this group. As creatinine clearance is often low in the elderly, consideration should be given to using a reduced dose in these patients. In the case of impaired renal function the dose must be reduced in accordance with the above table.

Duration of therapy.

The duration of the treatment for patients with herpes simplex encephalitis is at least ten days. The duration of treatment in patients with herpes simplex infections or patients with herpes zoster infection is usually five to seven days.

Administration.

Every dose should be administered by slow intravenous infusion over a one hour period. The preparation of the infusion fluid must be performed in two steps, reconstitution and dilution. Every vial of 250 mg should be reconstituted by adding either water for injections 10 mL or sodium chloride 0.9% w/v IV infusion 10 mL. Every vial of 500 mg should be reconstituted by adding either water for injections 20 mL or sodium chloride 0.9% w/v IV infusion 20 mL. The solvent should be at room temperature (15 to 25°C). In this way an IV stock solution containing aciclovir 25 mg/mL is obtained.
Aciclovir Sandoz IV Infusion (powder for injection) can be reconstituted for direct intravenousinjection over an hour by means of an infusion pump or can be further diluted for administration by infusion. The product should not be administered as a bolus injection.
The preparation of the solution for intravenous infusion is performed by diluting the aciclovir 25 mg/mL stock solution with one of the following infusion fluids: sodium chloride 0.9% w/v; sodium chloride 0.45% w/v and glucose 2.5% w/v; sodium chloride 0.18% w/v and glucose 4% w/v; glucose 5% w/v; Ringer lactate (Hartmann's solution).
The final aciclovir concentration in the infusion fluid should not exceed 5 mg/mL.
The product is preservative free. Reconstitution and dilution should be carried out immediately before use. For use in one patient and on one occasion only. Unused IV solutions must be destroyed as should solutions which preceding or during infusion opacificate or crystallise. The IV solution should not be refrigerated as this causes precipitation and crystallisation that is difficult to redisperse.

Overdosage

Contact the Poisons Information Centre on 131 126 for advice on the management of overdose.
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 overdosage. Adequate hydration is essential to reduce the possibility of crystal formation in the urine. Haemodialysis significantly enhances the removal of aciclovir from the blood and may, therefore, be considered an option in the management of overdose of this medicine.

Presentation

Powder for infusion, aciclovir sodium 274.4 mg (≡ aciclovir 250 mg), aciclovir sodium 548.8 mg (≡ aciclovir 500 mg): 20 mL (colourless glass vials with bromobutyl rubber stopper and aluminium flip cap).

Storage

Store the dry powder below 25°C in original product packaging. The product should be used immediately after reconstitution or dilution.

Poison Schedule

S4.