Lovrak Suspension is 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).
Lovrak Suspension is indicated for the suppression (prevention of
recurrences) of recurrent herpes simplex infections in
immunocompetent patients.
Lovrak Suspension is indicated for the prophylaxis of herpes
simplex infections in immunocompromised patients.
Lovrak Suspension is indicated for the treatment of varicella
(chickenpox) and herpes zoster (shingles) infections. Studies have
shown that early treatment of shingles with acyclovir has a
beneficial effect on pain and can reduce the incidence of postherpetic
neuralgia (zoster-associated pain).

Dosage for treatment of Herpes Simplex in Adults
For treatment of Herpes simplex infections, 200mg Lovrak 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 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 400mg Lovrak 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.
Dosage for suppression of Herpes simplex in adults
For suppression of Herpes simplex infections in immunocompetent
patients, 200mg Lovrak should be taken four times daily at
approximately six-hourly intervals.
Many patients may be conveniently managed on a regimen of
400mg Lovrak taken twice daily at approximately twelve-hourly
intervals.
Dosage titration down to 200mg Lovrak taken thrice daily at
approximately eight-hourly intervals or even twice daily at
approximately twelve-hourly intervals, may prove effective.
Some patients may experience break-through infections on total
daily doses of 800mg Lovrak.
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.
Dosage for prophylaxis of Herpes simplex in adults
For prophylaxis of Herpes simplex infections in
immunocompromised patients, 200mg Lovrak 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 400mg Lovrak or, alternatively,
intravenous dosing could be considered.
The duration of prophylactic administration is determined by the
duration of the period at risk.
Dosage for treatment of Varicella and Herpes zoster in adults
For treatment of Varicella and Herpes zoster infections, 800 mg
Lovrak should be taken five times daily at approximately fourhourly
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 the
infection; treatment yields better results if initiated as soon as
possible after onset of the rash.
Dosage for Infants and Children
For 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. Infants
and children below the age of two years should be given half the
adult dose.
For treatment of varicella infections for infants and children:
 6 years and over: 800 mg acyclovir four times daily
 2 - < 6 years: 400 mg acyclovir four times daily
 Under 2 years: 200 mg acyclovir four times daily
Treatment should continue for five days.
Dosing may be more accurately calculated as 20 mg/kg bodyweight
(not to exceed 800mg) acyclovir 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). Adequate hydration
should be maintained.
Dosage in renal impairment: Caution is advised when
administering acyclovir 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 acyclovir above levels that have been
established by intravenous infusion. However, for patients with
severe renal impairment (creatinine clearance less than 10
mL/minute) an adjustment of dosage to 200mg twice daily at
approximately twelve-hourly intervals is recommended.
In the treatment of Varicella and Herpes zoster infections it is
recommended that the dosage be adjusted to 800mg twice daily at
approximately twelve-hourly intervals for patients with severe
renal impairment (creatinine clearance less than 10mL/minute),
and to 800mg three times daily at intervals of approximately eight
hours for patients with moderate renal impairment (creatinine

clearance in the range 10-25 mL/minute).

Use in patients with renal impairment and in elderly patients:
Acyclovir is eliminated by renal clearance, therefore the dose must
be adjusted in patients with renal impairment (see section 4.2).
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 section 4.8).
Prolonged or repeated courses of acyclovir in severely immunecompromised
individuals may result in the selection of virus strains
with reduced sensitivity, which may not respond to continued
acyclovir treatment (see section 5.1).
Hydration status: Care should be taken to maintain adequate
hydration in patients receiving high oral doses of acyclovir.
Lovrak Suspension contains Methyl paraben and Propyl paraben
which may cause allergic reactions (possibly delayed).
Lovrak Suspension also contains sorbitol. Hence Patients with rare
hereditary problems of fructose intolerance should not take this
medicine.
 

No clinically significant interactions have been identified.
Acyclovir is eliminated primarily unchanged in the urine via active
renal tubular secretion. Any drugs administered concurrently that
compete with this mechanism may increase acyclovir plasma
concentrations. Probenecid and cimetidine increase the AUC of
acyclovir by this mechanism, and reduce acyclovir renal clearance.
Similarly increases in plasma AUCs of acyclovir and of the inactive
metabolite of mycophenolate mofetil, an immunosuppressant
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 acyclovir.

Fertility
See Clinical Studies in section 5.3
Pregnancy
The use of acyclovir should be considered only when the potential
benefits outweigh the possibility of unknown risks.
A post-marketing acyclovir pregnancy registry has documented
pregnancy outcomes in women exposed to any formulation of
acyclovir. The registry findings have not shown an increase in the
number of birth defects amongst acyclovir exposed subjects
compared with the general population, and any birth defects
showed no uniqueness or consistent pattern to suggest a common
cause.
Breast-feeding
Following oral administration of 200mg acyclovir five times a day,
acyclovir 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 acyclovir
dosages of up to 0.3 mg/kg/day. Caution is therefore advised if
acyclovir is to be administered to a nursing woman.
 

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

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.

To report any side effect(s):
 Saudi Arabia:
The National Pharmacovigilance and Drug Safety Centre (NPC)
Fax: +966-11-205-7662
Call NPC at +966-11-2038222, Exts: 2317-2356-2340
Reporting Hotline: 19999
E-mail: npc.drug@sfda.gov.sa
Website: www.sfda.gov.sa/npc
 Other GCC States: Please contact the relevant competent
authority

Symptoms & signs: Acyclovir is only partly absorbed in the gastrointestinal tract. Patients have ingested overdoses of up to 20g acyclovir on a single occasion, usually without toxic effects. Accidental, repeated overdoses of oral acyclovir over several days have been associated with gastrointestinal effects (such as nausea and vomiting) and neurological effects (headache and confusion).

Overdosage of intravenous acyclovir 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 acyclovir from the blood and may, therefore, be considered a management option in the event of symptomatic overdose.

Pharmacotherapeutic group: group Anti-infective, ATC code
J05AB01.
Mechanism of Action
Acyclovir 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), Epstein Barr virus (EBV) and cytomegalovirus
(CMV). In cell culture, acyclovir 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 acyclovir for HSV I, HSV II, VZV, EBV and
CMV is highly selective. The enzyme thymidine kinase (TK) of
normal, non-infected cells does not use acyclovir effectively as a
substrate, hence toxicity to mammalian host cells is low; however,
TK encoded by HSV, VZV and EBV converts acyclovir to acyclovir
monophosphate, a nucleoside analogue which is further converted
to the diphosphate and finally to the triphosphate by cellular

enzymes.

Acyclovir triphosphate interferes with the viral DNA polymerase
and inhibits viral DNA replication with resultant chain termination
following its incorporation into the viral DNA.
Pharmacodynamic Effects
Prolonged or repeated courses of acyclovir in severely
immunocompromised individuals may result in the selection of
virus strains with reduced sensitivity, which may not respond to
continued acyclovir treatment. Most of the clinical isolates with
reduced sensitivity have been relatively deficient in viral TK,
however, strains with altered viral TK or DNA polymerase have also
been reported. In vitro exposure of HSV isolates to acyclovir 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 acyclovir therapy is not clear.

Absorption
Acyclovir is only partially absorbed from the gut. Mean steady
state peak plasma concentrations (Cssmax) following doses of
200mg acyclovir administered four-hourly were 3.1 micromolar
(0.7 micrograms/mL) and equivalent trough plasma levels (Cssmin)
were 1.8 micromolar (0.4 micrograms/mL). Corresponding Cssmax
levels following doses of 400 mg and 800 mg administered fourhourly
were 5.3 micromolar (1.2 micrograms/mL) and 8
micromolar (1.8 micrograms/mL) respectively, and equivalent
Cssmin levels were 2.7 micromolar (0.6 micrograms/mL) and 4
micromolar (0.9 micrograms/mL). In adults the terminal plasma
half-life of acyclovir after administration of intravenous acyclovir is
about 2.9 hours. Most of the drug is excreted unchanged by the
kidney. Renal clearance of acyclovir 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 acyclovir, and accounts for approximately 10-15% of
the administered dose recovered from the urine. When acyclovir is
given one hour after 1 gram of probenecid the terminal half-life
and area under the plasma concentration-time curve is extended
by 18% and 40% respectively.
Elimination
In adults, mean Cssmax levels following a one hour infusion of 2.5
mg/kg, 5 mg/kg and 10mg/kg were 22.7 micromolar (5.1
micrograms/mL), 43.6 micromolar (9.8 micrograms/mL) and 92
micromolar (20.7 micrograms/mL), respectively. The
corresponding Cssmin levels 7 hours later were 2.2 micromolar
(0.5 micrograms/mL) 3.1 micromolar (0.7 micrograms/mL) and
10.2 micromolar (2.3 micrograms/mL), respectively. In children
over 1 year of age similar mean Cssmax and 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 10mg/kg. In
neonates and young infants (0-3 months of age) treated with doses
of 10 mg/kg administered by infusion over a one-hour period every
8 hours the Cssmax was found to be 61.2 micromolar (13.8
micrograms/mL) and the Cssmin to be 10.1 micromolar (2.3
micrograms/mL). 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 micrograms/mL)
and Cmin of 14.1 micromolar (3.2 micrograms/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
acyclovir half-life during haemodialysis was 5.7 hours. Plasma
acyclovir levels dropped approximately 60% during dialysis.
Distribution
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.

Fertility
There is no information on the effect of acyclovir oral formulations
or IV for infusion on human female fertility. In a study of 20 male
patients with normal sperm count, oral acyclovir 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.
Teratogenicity
Systemic administration of acyclovir 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.
Non-Clinical Information
Mutagenicity
The results of a wide range of mutagenicity tests in vitro and in
vivo indicate that acyclovir is unlikely to pose a genetic risk to man.
Carcinogenicity
Acyclovir was not found to be carcinogenic in long-term studies in
the rat and the mouse.
Fertility
Largely reversible adverse effects on spermatogenesis in
association with overall toxicity in rats and dogs have been
reported only at doses of acyclovir greatly in excess of those
employed therapeutically. Two-generation studies in mice did not
reveal any effect of (orally administered) acyclovir on fertility.

Inactive Ingredients:
1. Methyl Paraben
2. Propyl Paraben
3. Avicel RC 591
4. Glycerol
5. Sorbitol 70% Solution
6. Orange Banana Flavour
7. Purified Water

None known

Store below 30ºC.

120mL suspension in an amber glass bottle, provided with CRC cap,
packed in a printed carton along with a leaflet and measuring cup.

No special requirements.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.