Acyclovir Stella

Acyclovir.

Acyclovir (aciclovir) 200 mg, 400 mg or 800 mg.
Excipients/Inactive Ingredients: Microcrystalline cellulose, sodium starch glycolate, povidone K30, colloidal anhydrous silica, magnesium stearate.

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).
Suppression (prevention of recurrences) of recurrent herpes simplex infections in immunocompetent patients.
Prophylaxis of herpes simplex infections in immunocompromised patients.
Treatment of varicella (chickenpox) and herpes zoster (shingles) infections.

Dosage: 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 five 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 regime of 400 mg aciclovir twice daily at approximately twelve-hourly intervals.
Dosage titration down to 200 mg aciclovir taken three times 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 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.
Dosage in the 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 the adult doses 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: Children under 2 years should be given 200 mg four times daily.
Children aged 2-5 years should be given 400 mg four times daily.
Children aged 6 years and over should be given 800 mg four times daily.
Treatment should continue for 5 days.
Dosing may be more accurately calculated as 20 mg/kg bodyweight (not to exceed 800 mg four times daily).
A liquid formulation might be more suitable for small children.
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 as follows).
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 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).
Administration: Acyclovir STELLA is orally taken.

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

Hypersensitivity to aciclovir or valacyclovir, or to any of the excipients in the formula.

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. Further, 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.
Use in Elderly and patients with renal impairment: Aciclovir is eliminated by renal clearance, therefore the dose must be adjusted in patients with renal impairment.
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.
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.
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.
Use in Children: 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.

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.
Lactation: 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 0.3mg/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.

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 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 previously mentioned events are generally reversible and usually reported in patients with renal impairment or with other predisposing factors.
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.

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.
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.

Store in a well-closed container, in a dry place. Protect from light. Do not store above 30°C.

Antivirals

J05AB01 - aciclovir ; Belongs to the class of nucleosides and nucleotides excluding reverse transcriptase inhibitors. Used in the systemic treatment of viral infections.

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