MEDOVIR Powder for solution for infusion Ref.[28216] Active ingredients: Aciclovir

• The dose of Medovir i.v. must be adjusted in patients with impaired renal function in order to avoid accumulation of aciclovir in the body (see dosage in Renal impairment).
• In patients receiving Medovir i.v. at higher doses (e.g. for herpes encephalitis), specific care regarding renal function should be taken, particularly when patients are dehydrated or have any renal impairment.
• Reconstituted Medovir i.v. has a pH of approximately 11.0 and should not be administered by mouth.
• Medovir i.v. contains no antimicrobial preservative. Reconstitution and dilution should therefore be carried out under full aseptic conditions immediately before use. Any unused solution should be discarded. The reconstituted or diluted solutions should not be refrigerated.

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. However no dosage adjustment is necessary because of the wide therapeutic index of aciclovir.

In patients receiving intravenous Medovir, caution is required during concurrent administration 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 immunosuppressant agent used in transplant patients have been shown when the drugs are coadministered.

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

Pregnancy

A post-marketing aciclovir pregnancy registry has documented pregnancy outcomes in women exposed to any formulation of Medovir. The birth defects described amongst Medovir exposed subjects have not shown any uniqueness or consistent pattern to suggest a common cause.

Caution should however be exercised by balancing the potential benefits of treatment against any possible hazard.

Breast-feeding

Following oral administration of 200mg Medovir 5 times a day, aciclovir has been detected in breast milk at concentrations ranging form 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. Systemic administration of acyclovir in internationally accepted standard tests did not produce embryotoxic or teratogenic effects on in rats, rabbits or mice.

In a non-standard test in rats, foetal abnormalities were observed but only following such subcutaneous doses that maternal toxicity was produced. The clinical relevance of these findings is uncertain.

Limited human data show that the drug does not pass into breast milk following systemic administration.

Medovir has no influence on the ability to drive and use machines (see also 4.8).

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 1/1000 to <1/100, rare 1/10,000 to <1/1000, very rare <1/10,000, not known (cannot be estimated from the available data).

Blood and lymphatic system disorders

Uncommon: decrease in hematological indices (anemia, thrombocytopenia, and leucopenia).

Psychiatric and nervous system disorders

Very rare: dizziness, headache, agitation, confusion, tremor, ataxia, dysarthria, hallucinations, psychotic symptoms, convulsion, somnolence, encephalopathy, and coma. These are reversible and usually appear in medically complicated cases.

Immune system disorders

Very rare: anaphylaxis.

Vascular disorders

Common: phlebitis

Respiratory, thoracic and mediastinal disorders disorders

Very rare: dysponoea.

Gastrointestinal disorders

Common: Nausea and vomiting, reversible increases in liver-related enzymes

Very rare: diarrhoea, abdominal pain, reversible increases in bilirubin, jaundice, hepatitis.

Skin and subcutaneous tissue disorders

Common: pruritus, urticaria, rashes (including photosensitivity).

Very rare: angioedema.

Renal and urinary disorders

Common: rapid rises in creatinine and blood urea in patients administered aciclovir intravenously. It is thought these are related to peak plasma levels and degree of patient hydration. To avoid this effect, aciclovir should not be administered as a bolus, but given by slow infusion (over a 1 hour period), and the patient should be kept adequately hydrated.

Very rare: renal impairment, acute renal failure. If renal impairment develops during aciclovir intravenous therapy, in most cases it will rapidly respond to rehydration of patient, and/or dosage reduction or therapy withdrawal. In exceptional cases it can progress to acute renal failure.

General disorders and administration site conditions

Very rare: fatigue, fever, local inflammatory reactions.

Inadvertent infusion into extravascular tissues has led to severe local inflammatory reactions, including skin breakdown in some instances.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions is an important way to gather more information to continuously monitor the benefit/risk balance of the medicinal product. Any suspected adverse reactions should be reported to Pharmaceutical Services, Ministry of Health, CY-1475, www.moh.gov.cy/phs, Fax: +357 22608649.

Sterile aciclovir sodium is incompatible with biological or colloidal solutions. It is incompatible with hydroxybenzoate esters (parabens) and precipitation may occur.