4.1. Therapeutic indications

Aciclovir 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).

Aciclovir Suspension is indicated for the suppression (prevention of recurrences) of recurrent herpes simplex infections in immunocompetent patients.

Aciclovir Suspension is indicated for the prophylaxis of herpes simplex infections in immunocompromised patients.

Aciclovir Suspension is indicated for the treatment of varicella (chickenpox) and herpes zoster (shingles) infections. Studies have shown that early treatment of shingles with Aciclovir Suspension has a beneficial effect on pain and can reduce the incidence of post-herpetic neuralgia (zoster-associated pain).

4.2. Posology and method of administration

Dosage for treatment of herpes simplex in Adults:

For treatment of herpes simplex infections, 200mg Aciclovir suspension 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 400mg Aciclovir suspension 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 Aciclovir suspension should be taken FOUR times daily at approximately six-hourly intervals.

Many patients may be conveniently managed on a regimen of 400mg Aciclovir suspension twice daily at approximately twelve-hourly intervals.

Dosage titration down to 200mg Aciclovir suspension 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 infection on total daily doses of 800mg Aciclovir suspension.

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 Aciclovir suspension 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 Aciclovir suspension 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, 800mg Aciclovir suspension 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 yields better results if initiated as soon as possible after the 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. Do not dilute the oral suspension formulation.

For treatment of varicella infections for infants and children:

6 years and over: 800mg Aciclovir suspension four times daily.

2 to < 6 years: 400mg Aciclovir suspension four times daily.

Under 2 years: 200mg Aciclovir suspension four times daily.

Treatment should continue for five days.

Dosing may be more accurately calculated as 20mg/kg body weight (not to exceed 800mg) Aciclovir suspension 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 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 that 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 aciclovir twice daily at approximately twelve-hourly intervals is recommended.

In the treatment of varicella and herpes zoster infections it is recommended to adjust the dosage 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 to 25ml/minute).

Method of administration

For oral use only.

4.3. Contraindications

Aciclovir Suspension is contraindicated in patients known to be hypersensitive 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 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 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.

Excipients Warnings:

Sorbitol (E420): This medicinal product contains 1575mg sorbitol in each 5ml which is equivalent to 315mg/ml. Patients with hereditary fructose intolerance (HFI) should not take/be given this medicinal product.

Methyl parahydroxybenzoate (E218): May cause an allergic reaction (possibly delayed).

Propylene glycol (E1520): This medicinal product contains 5mg propylene glycol in each 5 ml which is equivalent to 1mg/ml.

4.5. Interaction with other medicinal products and other forms of interaction

No clinically significant interactions have been identified.

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 immunosuppressant agent used in transplant patients have been shown when the drugs are coadministered. However no dosage adjustment is necessary because of the wide therapeutic index of aciclovir.

4.6. Fertility, pregnancy and lactation

Pregnancy:

The use of acyclovir 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 suspension. 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.

Breast-feeding:

Following oral administration of 200mg 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 0.3mg/kg/day. Caution is therefore advised if Aciclovir suspension is to be administered to a nursing woman.

Fertility:

See clinical studies in Section 5.3

4.7. Effects on ability to drive and use machines

The clinical status of the patient and the adverse event profile of Aciclovir Suspension 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 Aciclovir Suspension 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. 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 to <1/10), uncommon ( ˃ 1/1,000 to <1/100), rare (˃ 1/10,000 to <1/1,000), 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

Very rare:

Agitation, confusion, tremor, ataxia, dysarthria, hallucinations, psychotic symptoms, convulsions, somnolence, encephalopathy, coma.

The above events are generally reversible and are usually reported in patients with renal impairment, or with other predisposing factors (see section 4.4 ).

Respiratory, thoracic and mediastinal disorders:

Rare:

Dyspnoea

Gastrointestinal disorders

Common:

Nausea, vomiting, diarrhoea, abdominal pains

Hepatobiliary 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 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 Website at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Symptoms & 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.