DBL™ Aciclovir Intravenous

Main information

  • Trade name:
  • DBL™ Aciclovir Intravenous 25 mg/mL Solution for infusion
  • Dosage:
  • 25 mg/mL
  • Pharmaceutical form:
  • Solution for infusion
  • Units in package:
  • Vial, glass, 5x10ml, 50 mL
  • Class:
  • Prescription
  • Prescription type:
  • Prescription
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug
  • Manufactured by:
  • Excella GmbH & Co KG

Documents

Localization

  • Available in:
  • DBL™ Aciclovir Intravenous 25 mg/mL Solution for infusion
    New Zealand
  • Language:
  • English

Therapeutic information

  • Therapeutic indications:
  • DBL Aciclovir intravenous infusion is indicated for:- treatment of Herpes simplex infections. - prophylaxis of Herpes simplex infections in immune-compromised patients. - treatment of Varicella zoster infections. - the treatment of Herpes simplex infections in the neonate. - prophylaxis of CMV infection in bone marrow transplant recipients. It has been shown that high dose intravenous aciclovir reduces the incidence and delays the onset of CMV infection. When high dose intravenous aciclovir is followed by 6 months treatment with high dose oral aciclovir (see prescribing information for oral aciclovir) mortality and the incidence of viraemia are also reduced.

Other information

Status

  • Source:
  • Medsafe - Medicines Safety Authority - New Zealand
  • Authorization number:
  • 7626
  • Authorization date:
  • 04-10-1995
  • Last update:
  • 27-09-2017

Summary of Product characteristics: dosage,interactions,side effects

Data Sheet – New Zealand

Version 5.0

DBL

ACICLOVIR INTRAVENOUS INFUSION

Name of medicine

Aciclovir sodium.

Presentation

Aciclovir Intravenous Infusion is a clear colourless or almost colourless sterile solution containing

the equivalent of 25 mg/mL of aciclovir in Water for Injections BP; the aciclovir is present as aciclovir

sodium. Sodium hydroxide (4.65 mg/mL) is included in the formulation. DBL

Aciclovir Intravenous

Infusion has a pH of approximately 11.

Uses

Actions

Aciclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against

human herpes viruses, including Herpes simplex virus types 1 and 2, Varicella zoster virus (VZV), Epstein

Barr virus (EBV) and Cytomegalovirus (CMV). In cell culture, aciclovir has the greatest antiviral activity

against HSV-1, followed (in decreasing order of potency) by HSV-2, VZV, EBV and CMV.

The inhibitory activity of aciclovir for HSV-1, HSV-2, VZV and EBV is highly selective. The enzyme

thymidine kinase (TK) of normal, uninfected cells does not use aciclovir effectively as a substrate, hence

toxicity to mammalian host cells is low; however, TK encoded by HSV, VZV and EBV converts aciclovir to

aciclovir monophosphate, a nucleoside analogue, which is further converted to the diphosphate and

finally to the triphosphate by cellular enzymes. Aciclovir triphosphate interferes with the viral DNA

polymerase and inhibits viral DNA replication with resultant chain termination following its incorporation

into the viral DNA.

Prolonged or repeated courses of aciclovir in severely immune-compromised individuals may result in the

selection of virus strains with reduced sensitivity, which may not respond to continued aciclovir treatment.

Most of the clinical isolates with reduced sensitivity have been relatively deficient in viral TK; however,

strains with altered viral TK or viral DNA polymerase have also been reported. In vitro exposure of HSV

isolates to aciclovir can also lead to the emergence of less sensitive strains. The relationship between the

in vitro determined sensitivity of HSV isolates and clinical response to aciclovir therapy is not clear. All

patients should be cautioned to ensure they avoid the potential of virus transmission, particularly when

active lesions are present.

Pharmacokinetics

In adults the terminal plasma half life of aciclovir is about 2.9 hours. Most of the medicine is excreted

unchanged by the kidney. Renal clearance of aciclovir is substantially greater than creatinine clearance

indicating that tubular secretion in addition to glomerular filtration contributes to the renal elimination of

the drug. 9-carboxymethoxy- methylguanine is the only significant metabolite of aciclovir and accounts for

approximately 10-15% of the dose excreted in the urine. When aciclovir is given one hour after 1 gram of

probenecid the terminal half life and the area under the plasma concentration time curve is extended by

18% and 40% respectively.

In adults, mean steady state peak plasma concentrations (C

ssmax

) following a one-hour infusion of 2.5

mg/kg, 5 mg/kg, 10 mg/kg and 15 mg/kg were 22.7 microM (5.1 mcg/mL), 43.6 microM (9.8 mcg/mL), 92

microM (20.7 mcg/mL) and 105 microM (23.6 mcg/mL), respectively. The corresponding trough levels

ssmin

) 7 hours later were 2.2 microM (0.5 mcg/mL), 3.1 microM (0.7 mcg/mL), 10.2 microM (2.3 mcg/mL)

and 8.8 microM (2.0 mcg/mL), respectively. In children over 1 year of age similar mean peak (C

ssmax

) and

trough (C

ssmin

) levels were observed when a dose of 250 mg/m

was substituted for 5 mg/kg and a dose

of 500 mg/m

was substituted for 10 mg/kg. In neonates (0-3 months of age) treated with doses of 10

mg/kg administered by infusion over a one-hour period every 8 hours the C

ssmax

was found to be 61.2

microM (13.8 mcg/mL) and the C

ssmin

to be 10.1 microM (2.3 mcg/mL). The terminal plasma half life in

these patients was 3.8 hours. In the elderly total body clearance falls with increasing age, associated with

decreases in creatinine clearance, although there is little change in the terminal plasma half life.

In patients with chronic renal failure the mean terminal half life was found to be 19.5 hours. The mean

aciclovir half life during haemodialysis was 5.7 hours. Plasma aciclovir levels dropped approximately 60%

during dialysis.

Data Sheet – New Zealand

Version 5.0

Cerebrospinal fluid levels are approximately 50% of corresponding plasma levels. Plasma protein binding

is relatively low (9 to 33%) and drug interactions involving binding site displacement are not anticipated.

Indications

Aciclovir Intravenous Infusion is indicated for the treatment of Herpes simplex infections.

Aciclovir Intravenous Infusion is indicated for the prophylaxis of Herpes simplex infections in

immune-compromised patients.

Aciclovir Intravenous Infusion is indicated in the treatment of Varicella zoster infections.

Aciclovir Intravenous Infusion is indicated for the treatment of Herpes simplex infections in the

neonate.

Aciclovir Intravenous Infusion formulations are indicated for prophylaxis of CMV infection in bone

marrow transplant recipients. It has been shown that high dose intravenous aciclovir reduces the

incidence and delays the onset of CMV infection. When high dose intravenous aciclovir is followed by 6

months treatment with high dose oral aciclovir (see prescribing information for oral aciclovir) mortality and

the incidence of viraemia are also reduced.

Dosage and administration

Dosage

Dosage in adults

Patients with Herpes simplex (except herpes encephalitis) or Varicella zoster infections should be given

Aciclovir Intravenous Infusion in doses of 5 mg/kg bodyweight every 8 hours.

Immune-compromised patients with Varicella zoster infections or patients with herpes encephalitis should

be given DBL

Aciclovir Intravenous Infusion in doses of 10 mg/kg bodyweight every 8 hours provided

renal function is not impaired.

For prophylaxis of CMV infection in bone marrow transplant recipients 500 mg/m

aciclovir should be

given intravenously 3 times daily at approximately 8 hourly intervals. The duration of treatment

recommended in bone marrow transplant recipients is from 5 days before up to 30 days after transplant.

Dosage in children

The dose of DBL

Aciclovir Intravenous Infusion for children aged between 3 months and 12 years is

calculated on the basis of body surface area.

Children with Herpes simplex (except herpes encephalitis) or Varicella zoster infections should be given

Aciclovir Intravenous Infusion in doses of 250 mg per square metre body surface area every 8

hours.

In immune-compromised children with Varicella zoster infections or children with herpes encephalitis,

Aciclovir Intravenous Infusion should be given in doses of 500 mg per square metre body surface

area every 8 hours if renal function is not impaired.

Limited data suggest that for the prophylaxis of CMV infection in children, over 2 years of age, who have

undergone bone marrow transplantation, the adult dose may be given.

Children with impaired renal function require an appropriately modified dose, according to the degree of

impairment.

Dosage in Neonates

The dosage of DBL

Aciclovir Intravenous Infusion in neonates is calculated on the basis of bodyweight.

Neonates with Herpes simplex infections should be given DBL

Aciclovir Intravenous Infusion in doses of

10 mg/kg bodyweight every 8 hours.

Data Sheet – New Zealand

Version 5.0

Dosage in the Elderly

In the elderly total aciclovir body clearance declines in parallel with creatinine clearance. Special attention

should be given to dosage reduction in elderly patients with impaired creatinine clearance.

Dosage in Renal Impairment

Caution is advised when administering DBL

Aciclovir Intravenous Infusion to patients with impaired renal

function. The following adjustments in dosage are suggested.

Creatinine Clearance

Dosage

25-50 mL/min

The dose recommended above (5 or 10 mg/kg bodyweight or 500

mg/m

) should be given every 12 hours.

10-25 mL/min

The dose recommended above (5 or 10 mg/kg bodyweight or 500

mg/m

) should be given every 24 hours.

0 (anuric)-10 mL/min

In patients receiving continuous ambulatory peritoneal dialysis

(CAPD) the dose recommended above (5 or 10 mg/kg bodyweight or

500 mg/m

) should be halved and administered every 24 hours. In

patients receiving haemodialysis the dose recommended above (5 or

10 mg/kg bodyweight or 500 mg/m

) should be halved and

administered every 24 hours and after dialysis.

A course of treatment with DBL

Aciclovir Intravenous Infusion usually lasts 5 days, but this may be

adjusted according to the patient's condition and response to therapy. Treatment for herpes encephalitis

and neonatal Herpes simplex infections usually lasts 10 days.

The duration of prophylactic administration of DBL

Aciclovir Intravenous Infusion is determined by the

duration of the period at risk.

Administration

The required dose of DBL

Aciclovir Intravenous Infusion should be administered by slow intravenous

infusion over a one-hour period.

From the calculated dose, determine the appropriate number of vials to be used. To reconstitute each

vial, add the recommended volume of infusion fluid and shake gently until the contents of the vial have

dissolved completely.

After reconstitution DBL

Aciclovir Intravenous Infusion may be administered by a controlled-rate infusion

pump.

Alternatively, the reconstituted solution may be further diluted to give an aciclovir concentration of not

greater than 5 mg/mL (0.5%w/v) for administration by infusion

Add the required volume of reconstituted solution to the chosen infusion solution, as recommended

below, and shake well to ensure adequate mixing occurs.

For children and neonates, where it is advisable to keep the volume of infusion fluid to a minimum, it is

recommended that dilution is on the basis of 4 mL reconstituted solution (100 mg aciclovir) added to 20

mL of infusion fluid.

For adults, it is recommended that infusion bags containing 100 mL of infusion fluid are used, even when

this would give an aciclovir concentration substantially below 0.5%w/v. Thus one 100 mL infusion bag

may be used for any dose between 250 mg and 500 mg aciclovir (10 and 20 mL of reconstituted solution)

but a second bag must be used for doses between 500 and 1000 mg.

When diluted in accordance with the recommended schedules, DBL

Aciclovir Intravenous Infusion is

known to be compatible with the following infusion fluids and stable for up to 12 hours at room

temperature (15°C to 25°C).

Sodium Chloride Intravenous Infusion BP (0.45% and 0.9% w/v);

Sodium Chloride (0.18% w/v) and Glucose (4% w/v) Intravenous Infusion BP;

Sodium Chloride (0.45% w/v) and Glucose (2.5% w/v) Intravenous Infusion BP;

Data Sheet – New Zealand

Version 5.0

Compound Sodium Lactate Intravenous Infusion BP (Hartmann's Solution).

Aciclovir Intravenous Infusion when diluted in accordance with the above schedule will give an

aciclovir concentration not greater than 0.5% w/v.

Since no antimicrobial preservative is included, reconstitution and dilution must be carried out under full

aseptic conditions, immediately before use, and any unused solution discarded.

Should any visible turbidity or crystallisation appear in the solution before or during infusion, the

preparation should be discarded.

Contraindications

Aciclovir Intravenous Infusion is contraindicated in patients known to be previously hypersensitive

to aciclovir or valaciclovir.

Warnings and precautions

The dose of DBL

Aciclovir Intravenous Infusion must be adjusted in patients with impaired renal function

in order to avoid accumulation of aciclovir in the body (See Dosage in renal impairment).

In patients receiving DBL

Aciclovir Intravenous Infusion at higher doses (e.g. for herpes encephalitis),

specific care regarding renal function should be taken, particularly when patients are dehydrated or have

any renal impairment.

Reconstituted DBL

Aciclovir Intravenous Infusion has a pH of approximately 11.0 and should not be

administered by mouth.

Pregnancy and Lactation

Pregnancy

Limited data are available on the use of aciclovir during pregnancy.

Caution should therefore be exercised by balancing the potential benefits of treatment against any

possible hazard.

Lactation

Following oral administration of 200 mg five times a day, aciclovir has been detected in human breast

milk at concentrations ranging from 0.6 to 4.1 times the corresponding plasma levels. These levels would

potentially expose nursing infants to aciclovir dosages of up to 0.3 mg/kg bodyweight/ day. Caution is

therefore advised if aciclovir is to be administered to a nursing woman.

Teratogenicity

Systemic administration of aciclovir in internationally accepted standard tests did not produce

embryotoxic or teratogenic effects in rabbits, rats or mice.

In a non-standard test in rats, foetal abnormalities were observed but only following such high

subcutaneous doses that maternal toxicity was produced. The clinical relevance of these findings is

uncertain.

Fertility

Largely reversible adverse effects on spermatogenesis in association with overall toxicity in rats and dogs

have been reported only at doses of aciclovir greatly in excess of those employed therapeutically. Two-

generation studies in mice did not reveal any effect of (orally administered) aciclovir on fertility.

There is no experience of the effect of DBL

Aciclovir Intravenous Infusion on human fertility. Aciclovir

Tablets have been shown to have no definitive effect upon sperm count, morphology or motility in man.

Effects on ability to drive and use machines

No data available.

Data Sheet – New Zealand

Version 5.0

Other

Mutagenicity

The results of a wide range of mutagenicity tests in vitro and in vivo indicate that aciclovir is unlikely to

pose a genetic risk to man.

Carcinogenicity

Aciclovir was not found to be carcinogenic in long-term studies in the rat and the mouse.

Adverse effects

Gastrointestinal:

Nausea and vomiting have been reported.

Haematological:

Decreases in haematological indices (anaemia, thrombocytopenia, leucopenia).

Hypersensitivity and skin:

Rashes including photosensitivity, urticaria, pruritus, fevers and rarely

dyspnoea, angioedema and anaphylaxis

Severe local inflammatory reactions sometimes leading to breakdown of the skin have occurred when

Aciclovir Intravenous Infusion has been inadvertently infused into extravascular tissues.

Kidney:

Rapid increases in blood urea and creatinine levels may occasionally occur in patients given

Aciclovir Intravenous Infusion. This is believed to be related to peak plasma levels and the state of

hydration of the patient. To avoid this effect the medicine should not be given as an intravenous bolus

injection but by slow infusion over a one-hour period.

Adequate hydration of the patient should be maintained. Renal impairment developing during treatment

with DBL

Aciclovir Intravenous Infusion usually responds rapidly to rehydration of the patient and/or

dosage reduction or withdrawal of the medicine. Progression to acute renal failure, however, can occur in

exceptional cases.

Liver:

Reversible increases in bilirubin and liver-related enzymes. Hepatitis and jaundice have been

reported on very rare occasions.

Neurological:

Reversible neurological reactions such as confusion, hallucinations, agitation, tremors,

somnolence, psychosis, convulsions and coma have been associated with DBL

Aciclovir Intravenous

Infusion therapy, usually in medically complicated cases.

Interactions

No clinically significant interactions have been identified.

Aciclovir is eliminated primarily unchanged in the urine via active renal tubular secretion. Any medicines

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 intravenous aciclovir, 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 intravenous aciclovir

with medicines which affect other aspects of renal physiology (e.g. cyclosporin, tacrolimus).

Overdosage

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

Data Sheet – New Zealand

Version 5.0

and coma have been described in association with overdosage. 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.

Pharmaceutical precautions

Instructions for Use/Handling

Aciclovir Intravenous Infusion contains no preservative. Dilution should therefore be carried out

immediately before use and any unused solution should be discarded. Should visible turbidity or

crystallisation appear in the solution before or during infusion the preparation should be discarded.

THE SOLUTION SHOULD NOT BE REFRIGERATED as this causes precipitation of crystals. These

crystals usually do not redissolve when solution temperature is brought to room temperature.

Incompatibilities

See Dosage and Administration.

Special Precautions for Storage

Store below 25°C. Do not refrigerate.

Medicine classification

Prescription Medicine.

Package quantities

Strength

Pack Size

aciclovir 250 mg/10 mL

aciclovir 500 mg/20 mL

Further information

Aciclovir sodium is a synthetic acyclic purine nucleoside analogue. Its chemical name is 9-[(2-

hydroxyethoxy)-methyl] guanine sodium. Aciclovir sodium is a white crystalline powder with a molecular

weight (MW) of 247.2.

The chemical structure of aciclovir sodium (CAS 69657-51-8) is shown below.

Name and address

Pfizer New Zealand Limited,

PO Box 3998

Auckland, New Zealand, 1140

Toll Free Number: 0800 736 363

Data Sheet – New Zealand

Version 5.0

Date of preparation

24 July 2017

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