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ACICLOVIR 800 MG TABLETS

Active substance(s): ACICLOVIR / ACICLOVIR

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Aciclovir 800 mg Tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 800 mg tablet contains 800mg Aciclovir.
For the full list of excipients, see section 6.1

3

PHARMACEUTICAL FORM
Tablet
Capsule shaped biconvex uncoated white to off-white tablets with “800” debossed on
one side and “ACV” on the other side.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Aciclovir Tablets are indicated for the treatment of herpes simplex virus
infections of the skin and mucous membranes including initial and recurrent
genital herpes (excluding neonatal HSV and severe HSV infections in
immunocompromised children).
Aciclovir Tablets are indicated for the suppression (prevention of recurrences)
of recurrent herpes simplex infections in immunocompetent patients.
Aciclovir Tablets are indicated for the prophylaxis of herpes simplex
infections in immunocompromised patients.
Aciclovir Tablets are indicated for the treatment of varicella (chickenpox) and
herpes zoster (shingles) infections.

4.2

Posology and method of administration
Posology

Dosage in adults
Treatment of herpes simplex infections: 200 mg Aciclovir should be taken five times
daily at approximately four hourly intervals omitting the night time dose. Treatment
should continue for 5 days, but in severe initial infections this may have to be
extended.
In severely immunocompromised patients (e.g. after marrow transplant) or in patients
with impaired absorption from the gut the dose can be doubled to 400 mg Aciclovir,
or alternatively, intravenous dosing could be considered.
Dosing should begin as early as possible after the start of an infection; for recurrent
episodes this should preferably be during the prodromal period or when lesions first
appear.
Suppression of herpes simplex infections in immunocompetent patients: 200 mg
Aciclovir should be taken four times daily at approximately six-hourly intervals.
Many patients may be conveniently managed on a regimen of 400 mg Aciclovir twice
daily at approximately twelve-hourly intervals.
Dosage titration down to 200 mg Aciclovir taken thrice daily at approximately eighthourly intervals or even twice daily at approximately twelve-hourly intervals may
prove effective.
Some patients may experience break-through infection on total daily doses of 800 mg
Aciclovir.
Therapy should be interrupted periodically at intervals of six to twelve months, in
order to observe possible changes in the natural history of the disease.
Prophylaxis of herpes simplex infections in immunocompromised patients: 200 mg
Aciclovir should be taken four times daily at approximately six-hourly intervals.
In severely immunocompromised patients (e.g. after marrow transplant) or in patients
with impaired absorption from the gut, the dose can be doubled to 400 mg Aciclovir,
or alternatively, intravenous dosing could be considered.
The duration of prophylactic administration is determined by the duration of the
period at risk.
Treatment of varicella and herpes zoster infections: 800 mg Aciclovir should be taken
five times daily at approximately four-hourly intervals, omitting the night time dose.
Treatment should continue for seven days.
In severely immunocompromised patients (e.g. after marrow transplant) or in patients
with impaired absorption from the gut, consideration should be given to intravenous
dosing.
Dosing should begin as early as possible after the start of an infection: Treatment of
herpes zoster yields better results if initiated as soon as possible after the onset of the
rash. Treatment of chickenpox in immunocompetent patients should begin within 24
hours after onset of the rash.
Paediatric population
Treatment of herpes simplex infections, and prophylaxis of herpes simplex infections
in the immunocompromised: Children aged two years and over should be given adult
dosages and children below the age of two years should be given half the adult dose.
For treatment on neonatal herpes virus infections, intravenous aciclovir is
recommended.
Treatment of varicella infection
6 years and over: 800 mg Aciclovir four times daily
2 - 5 years: 400 mg Aciclovir four times daily

Under 2 years: 200 mg Aciclovir four times daily
Treatment should continue for five days.
Dosing may be more accurately calculated as 20 mg/kg bodyweight (not to exceed
800 mg) Aciclovir four times daily.
No specific data are available on the suppression of herpes simplex infections or the
treatment of herpes zoster infections in immunocompetent children.
Dosage in the elderly
The possibility of renal impairment in the elderly must be considered and the dosage
should be adjusted accordingly (see Dosage in renal impairment below). Adequate
hydration of elderly patients taking high oral doses of Aciclovir should be
maintained.
Dosage in renal impairment
Caution is advised when administering aciclovir to patients with impaired renal
function. Adequate hydration should be maintained.
In the management of herpes simplex infections in patients with impaired renal
function, the recommended oral doses will not lead to accumulation of aciclovir
above levels that have been established safe by intravenous infusion. However for
patients with severe renal impairment (creatinine clearance less than 10 ml/minute) an
adjustment of dosage to 200 mg aciclovir twice daily at approximately twelve-hourly
intervals is recommended.
In the treatment of herpes zoster infections it is recommended to adjust the dosage to
800 mg aciclovir twice daily at approximately twelve hourly intervals for patients
with severe renal impairment (creatinine clearance less than 10 ml/minute), and to
800 mg aciclovir three times daily at intervals of approximately eight hours for
patients with moderate renal impairment (creatinine clearance in the range 10 – 25
ml/minute).
Method of administration:
Oral.
Aciclovir tablets may be dispersed in a minimum of 50 ml of water or swallowed
whole with a little water. Ensure that patients on high doses of aciclovir are
adequately hydrated.

4.3

Contraindications
Hypersensitivity to aciclovir or valaciclovir, or to any of the excipients listed in
section 6.1.

4.4

Special warnings and precautions for use
Use in patients with renal impairment and in elderly patients:
Aciclovir is eliminated by renal clearance, therefore the dose must be adjusted in
patients with renal impairment (see 4.2 Posology and Method of Administration).

Elderly patients are likely to have reduced renal function and therefore the need for
dose adjustment 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 4.8 Undesirable Effects).
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 (see section 5.1).
Hydration status: Care should be taken to maintain adequate hydration in patients
receiving high oral doses of aciclovir.
The risk of renal impairment is increased by use with other nephrotoxic drugs.
The data currently available from clinical studies is not sufficient to conclude that
treatment with aciclovir reduces the incidence of chickenpox-associated
complications in immunocompetent patients.
Paediatric population:
Oral aciclovir should be used in paediatric population mainly for the treatment of
non-severe skin and mucosa HSV infections. For the treatment of neonatal HSV and
severe HSV infections in immunocompromised children IV aciclovir should be used.

4.5

Interaction with other medicinal products and other forms of interaction

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. Similarly
increases in plasma AUCs of aciclovir and of the inactive metabolite of
mycophenolate mofetil, an immunosuppresant agent used in transplant patients have
been shown when the drugs are co administered. However no dosage adjustment is
necessary because of the wide therapeutic index of aciclovir.
An experimental study on five male subjects indicates that concomitant therapy with
aciclovir increases AUC of totally administered theophylline with approximately
50%. It is recommended to measure plasma concentrations during concomitant
therapy with aciclovir.
4.6

Fertility, pregnancy and lactation
Pregnancy
The use of aciclovir should be considered only when the potential benefits outweigh
the possibility of unknown risks. A post-marketing aciclovir pregnancy registry has
documented pregnancy outcomes in women exposed to any formulation of Aciclovir.
The registry findings have not shown an increase in the number of birth defects

amongst aciclovir exposed subjects compared with the general population, and any
birth defects showed no uniqueness or consistent pattern to suggest a common cause.
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.
Caution should however be exercised by balancing the potential benefits of treatment
against any possible hazard. Findings from reproduction toxicology studies are
included in Section 5.3.
Breastfeeding
Following oral administration of 200 mg Aciclovir five times a day, aciclovir has
been detected in 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/day. Caution is therefore advised if aciclovir is
to be administered to a nursing woman.
Fertility
There is no information on 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 1g per day for up to six months has been shown to have no clinically
significant effect on sperm count, motility or morphology.
See clinical studies in section 5.2

4.7

Effects on ability to drive and use machines
There have been no studies to investigate the effect of aciclovir on driving
performance or the ability to operate machinery. A detrimental effect on such
activities cannot be predicted from the pharmacology of the active substance, but the
adverse event profile should be borne in mind.

4.8

Undesirable 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 ≥
1/1000 and < 1/100, rare ≥ 1/10,000 and < 1/1000, very rare < 1/10,000
Blood and the lymphatic system disorders:
Very rare: Anaemia, leukopenia, thrombocytopenia.
Immune system disorders:

Rare: Anaphylaxis.
Psychiatric and nervous system disorders:
Common: Headache, dizziness.
Very rare: Agitation, confusion, tremor, ataxia, dysarthria, hallucinations, psychotic
symptoms, convulsions, somnolence, encephalopathy, coma.
The above events are generally reversible and usually reported in patients with renal
impairment or with other predisposing factors (see 4.4 Special Warnings and
Precautions for Use).
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 and crystalluria.
General disorders and administration site conditions:
Common: fatigue, fever.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation 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
via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9

Overdose
Symptoms and signs
Aciclovir is only partly absorbed in the gastrointestinal tract. Patients have
ingested overdoses of up to 20g 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. Haemodialysis significantly
enhances the removal of aciclovir from the blood and may, therefore, be considered a
management option in the event of symptomatic overdose

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Direct acting antivirals, Nucleosides and nucleotides
excl. reverse transcriptase inhibitors.
ATC code: J05AB01
Aciclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory
activity against human herpes viruses, including herpes simplex virus (HSV) types I
and II and varicella zoster virus (VZV).
The inhibitory activity of aciclovir for HSV I, HSV II and VZV is highly selective.
The enzyme thymidine kinase (TK) of normal, uninfected cells does not use aciclovir
effectively as a substrate, hence toxicity of mammalian host cells is low; however,
TK encoded by HSV and VZV 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 immuno-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.

5.2

Pharmacokinetic properties
Aciclovir is only partially absorbed from the gut. Mean steady state peak plasma
concentrations (Cssmax) following doses of 200 mg administered four-hourly were
3.1 microMol (0.7 micrograms/ml) and equivalent trough plasma levels (Cssmin) were
1.8 microMol (0.4 micrograms/ml). Corresponding Cssmax levels following doses of
400 mg and 800 mg administered four-hourly were 5.3 microMol (1.2
micrograms/ml) and 8 microMol (1.8 micrograms/ml) respectively and equivalent
Cssmin levels were 2.7 microMol (0.6 micrograms/ml) and 4 microMol (0.9
micrograms/ml).

In adults the terminal plasma half-life of aciclovir after administration of intravenous
aciclovir is about 2.9 hours. Most of the drug 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-carboxymethoxymethylguanine is the only significant
metabolite of aciclovir, and accounts for approximately 10 - 15% of the administered
dose recovered from 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 (Cssmax) following a one
hour infusion of 2.5 mg/kg, 5 mg/kg and 10 mg/kg were 22.7 microMol (5.1
micrograms/ml), 43.6 microMol (9.8 micrograms/ml) and 92 microMol (20.7
micrograms/ml), respectively. The corresponding trough levels (Cssmin) 7 hours later
were 2.2 microMol (0.5 micrograms/ml), 3.1 microMol (0.7 micrograms/ml), and
10.2 microMol (2.3 micrograms/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 neonates and young infants (0 to 3
months of age) treated with doses of 10 mg/kg administered by infusion over a onehour period every 8 hours the Cssmax was found to be 61.2 microMol (13.8
micrograms/ml) and Cssmin to be 10.1 microMol (2.3 micrograms/ml). The terminal
plasma half-life in these patients was 3.8 hours. A separate group of neonates treated
with 15 mg/kg every 8 hours showed approximate dose proportional increases, with a
Cmax of 83.5 micromolar (18.8 microgram/ml) and Cmin of 14.1 micromolar (3.2
microgram/ml).
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.
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.

5.3

Preclinical safety data
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.
Teratogenicity:
Systemic administration of aciclovir in internationally accepted standard tests
did not produce embryotoxic or teratogenic effects in rats, rabbits 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 aciclovir on fertility.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Magnesium stearate
Microcrystalline cellulose
Sodium starch glycollate
Pregelatinised starch
Colloidal anhydrous silica

6.2

Incompatibilities
Not applicable

6.3

Shelf life
3 years

6.4

Special precautions for storage
No special storage conditions are required

6.5

Nature and contents of container

Blister strips comprising of plain aluminium foil and PVdC coated PVC film.

Pack sizes:35 tablets/carton, 60 tablets/carton & 100 tablets/carton.
Not all pack sizes may be marketed.
6.6

Special precautions for disposal
Not applicable.

7

MARKETING AUTHORISATION HOLDER
Ranbaxy (UK) Limited
5th floor, Hyde Park, Hayes 3
11 Millington Road
Hayes, UB3 4AZ
United Kingdom

8

MARKETING AUTHORISATION NUMBER(S)
PL 14894/0009

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
17/07/2007

10

DATE OF REVISION OF THE TEXT
24/05/2017

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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