DNA polymerase inhibitors (antivirals).

Generic

Each vial contains 250mg Aciclovir (as the sodium salt) in a freeze-dried sterile powder form.

Powder for Solution for Infusion Sterile powder for infusion packaged in colourless 20ml glass vials

• Treatment and prophylaxis of Herpes simplex virus infections in immunocompromised patients.
• Treatment of severe initial genital herpes in non-immunocompromised patients.
• Treatment of Herpes simplex encephalitis.
• Treatment of Varicella zoster infections.
• Treatment of Herpes simplex infections in the neonate and in infants up to age 3 months.
  

Route of administration: Slow intravenous infusion

The duration of intravenous therapy with Aciclovir is usually 5 days and may be adjusted in accordance with the condition of the patient and the response to therapy. For herpes encephalitis and neonatal Herpes simplex infections, the duration of therapy is usually 10 days.

When used for prophylaxis, the duration of intravenous administration of Aciclovir is determined by the duration of the risk period.

Dosage in adults : The recommended dosage for adults with Herpes simplex (excluding herpes encephalitis) or Varicella zoster infections is 5mg per kg bodyweight every 8 hours, provided that renal function is not impaired.

Immunocompromised patients with Varicella zoster infections or patients with herpes encephalitis should be given Aciclovir intravenously in doses of 10mg per kg bodyweight every 8 hours, provided that renal function is not impaired.

Dosage in children : The recommended dosage for children with Herpes simplex (excluding herpes encephalitis) or Varicella zoster infections is 250mg per square metre of body surface area every 8 hours.

Immunocompromised children with Varicella zoster infections or children with herpes encephalitis should be given Aciclovir intravenously in doses of 500mg per square metre of body surface area every 8 hours if renal function is not impaired.

For children with renal impairment, the dosage should be modified, appropriately, according to the degree of impairment.

Dosage in neonates and infants up to age 3 months : The recommended dosage for treatment of Herpes simplex infections is 10mg per kg bodyweight every 8 hours. For neonatal Herpes simplex infections, the usual duration of treatment is 10 days.

Dosage in the elderly: The total body clearance of Aciclovir in the elderly declines in parallel with creatinine clearance. In elderly patients with impaired creatinine clearance, particular attention should be given to dosage reduction.

Dosage in renal impairment: Particular care should be taken when administering Aciclovir intravenously to patients with impaired renal function. Dosage adjustments are suggested as follows:

Orally: Herpes simplex treatment and prophylaxis: under two years, give half adult dose; over two years, give adult dose. Varicella and herpes zoster  of 800mg given four times a day for five days. Alternatively, under two years, 200mg four times a day; two to five years, 400mg four times a day; over six years, 800mg four times a day. IV Infusion: Herpes simplex: Neonates up to three months, 10mg/kg body weight every eight hours for 10 days; over three months to 12 years, 250mg/m 2 every eight hours for five days. Varicella zoster: Three months to 12 years, 250mg/m2 every eight hours for five days. This can be inreased to 500mg/m 2 in immunocompromised. Simplex encephalitis: Three months to 12 years, 500mg/m 2 every eight hours for 10 days.

Known hypersensitivity to aciclovir.

If renal function is impaired, the intravenous dose must be adjusted in order to avoid accumulation of Aciclovir in the body.

When higher doses of Aciclovir are administered (e.g. for herpes encephalitis), specific care, regarding renal function should be exercised, especially if the patient is dehydrated or has any renal impairment.

The reconstituted solution is highly alkaline and should not be administered orally.

Aciclovir Powder for Infusion 250mg does not contain an antimicrobial preservative. Reconstitution and dilution should, therefore, be performed under full aseptic conditions,immediately before use, and any unused solution should be discarded. Reconstituted or diluted solutions should not be refrigerated.

Other warnings and precautions:

The labels shall contain the following statements:

For intravenous infusion only

Keep out of reach of children

Do not store above 25°C

After reconstitution and dilution use immediately

Discard any unused portion

Patients must maintain adequate hydration throughout treatment. Reduce dose in moderate to severe renal impairment. Pregnancy and lactation.

No clinically significant interactions have been identified.

Aciclovir is eliminated mainly unchanged in the urine via active renal tubular secretion. Concomitant administration of any drugs that compete with this mechanism may increase aciclovir plasma concentrations. Probenecid and cimetidine increase the AUC of acyclovir by this mechanism, and reduce its renal clearance. However no dosage adjustment is necessary because of the wide therapeutic index of aciclovir.

Caution is required during concurrent intravenous administration of aciclovir with drugs which compete with aciclovir for elimination, because of the potential for increased plasma levels of one or both drugs or their metabolites. 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.

Care is also required, including monitoring for changes in renal function, if administering intravenous aciclovir with drugs which affect other aspects of renal physiology (e.g. cyclosporin, tacrolimus)

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 I.V. has been inadvertently infused in extravascular tissues.

Kidney: Rapid increases in blood urea and creatinine levels may occasionally occur in patients given aciclovir I.V., putatively in relation to peak plasma levels and the state of hydration of the patient. To avoid this effect the drug should be given by slow infusion over a one hour period, and not as an intravenous bolus injection.

Adequate hydration of the patient should be maintained. If renal impairment develops during intravenous administration of aciclovir, it usually responds rapidly to rehydration of the patient and/or dosage reduction or withdrawal of the drug. 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 reaction such as confusion, hallucinations, agitation, tremors, somnolence, psychosis, convulsions and coma have been associated with acyclovir I.V. therapy, usually in medically complicated cases.

Goldshield plc

(POM)

22 July 2009