ACICLOVIR EG 5 % Cr T/10g

Aciclovir............................................................................................................................................................... 5 g

For 100 g of cream.

Excipients with known effect:

Each gram of cream contains 150 mg propylene glycol and 15 mg cetyl alcohol.

Treatment of herpes simplex virus skin infections, in particular genital herpes, in immunocompetent patients.

• ACICLOVIR EG 5 PERCENT, cream should be applied to the infected skin 5 times a day, approximately every 4 hours, avoiding application at night.
• ACICLOVIR EG 5 PERCENT, cream should be applied to existing or developing lesions as early as possible after the onset of infection.
• Treatment should be continued for 5 days. If after 5 days healing is not complete, treatment may be continued for an additional 5 days.

Hypersensitivity to the active substance, to valaciclovir or to any of the excipients listed in the section Composition

To avoid local irritation, avoid applying the cream to mucous membranes (oral, vaginal and ocular). Avoid accidental contact with the eyes.

Patients with genital herpes should refrain from all sexual intercourse while lesions are visible, in order to avoid transmission of the infection to their partners.

The severity of recurrent infections depends on the patient's immune status, the duration and frequency of episodes, the total surface area of lesions, and whether or not systemic reactions are present. Management of the patient should take these factors into account and therefore include either advice and symptomatic treatment, or aetiological treatment. Severe cases of primary genital herpes infection should be treated with oral aciclovir. The physical, emotional and psychosocial problems that may result from a herpes infection differ from one patient to another. The choice of treatment will therefore depend on each patient's individual situation.

In severely immunocompromised patients (for example: patients with AIDS or bone marrow transplant recipients), oral aciclovir treatment should be considered. Such patients should be advised to consult their physician for the treatment of any infection.

Excipients

Propylene glycol (E1520) may cause skin irritation. This medicine should not be used in babies under 4 weeks of age who have open wounds or large areas of damaged or injured skin (burns). 

Cetyl alcohol may cause local skin reactions (for example contact dermatitis).

Pregnancy

The use of aciclovir should only be considered if the expected benefits outweigh the potential risks; nevertheless, systemic exposure following topical application of aciclovir is very low.

Post-marketing data from a pregnancy registry have documented the outcome of pregnancies in women exposed to any pharmaceutical form of aciclovir. The results of this registry did not show an increase in the number of cases of congenital anomalies compared with the general population; the anomalies observed had no typical characteristics or similarities suggesting a common cause.

Animal studies have demonstrated harmful effects of aciclovir. In internationally accepted standardised tests, systemic administration of aciclovir did not produce embryotoxic or teratogenic effects in rabbits, rats or mice. Foetal abnormalities were observed in a non-standardised test in rats, but only at very high subcutaneous doses, associated with maternal toxicity.

The clinical significance of these findings is uncertain.

Breast-feeding

Limited data have shown that aciclovir passes into breast milk after systemic administration. However, the dose received by a breastfed infant following use of aciclovir cream by the mother is expected to be very low.

No study has been carried out on the effects of ACICLOVIR EG 5 PER CENT, cream on the ability to drive vehicles or use machines. However, an undesirable effect on these activities is unlikely.

The frequency of undesirable effects is defined as follows: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1 000, < 1/100); rare (≥ 1/10 000, < 1/1 000); very rare (< 1/10 000).

Immune system disorders

Very rare: immediate hypersensitivity reactions including angioedema and urticaria.

Skin and subcutaneous tissue disorders 

Uncommon: transient sensations of burning or tingling at the application site, slight dryness or desquamation, pruritus.

Rare: erythema, contact dermatitis after application. Hypersensitivity tests showed that the sensitising substances were mainly the excipients and not aciclovir itself.

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 reaction via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Centres of Pharmacovigilance - Website: www.signalement-sante.gouv.fr.

No undesirable effects are noted in the case of ingestion of the entire content of a tube of 10 g of cream containing 500 g of aciclovir.

Doses of 800 mg 5 times per day were administered orally for 7 days in the treatment of herpes zoster without adverse effects.

Pharmacotherapeutic class: ANTIVIRAL FOR TOPICAL USE, ATC code: D06BB03.

Aciclovir itself is a pharmacodynamically inactive compound. After penetrating cells infected with herpes simplex virus (HSV), aciclovir is converted into its active form, aciclovir triphosphate. This conversion is catalysed by the HSV thymidine kinase, an enzyme essential for viral replication. HSV thus ensures the synthesis of its own antiviral agent. The affinity of aciclovir for cellular DNA polymerase.

Aciclovir thus selectively inhibits viral enzymatic activity. Viral DNA polymerase incorporates aciclovir into viral DNA.

Aciclovir lacks a 3'-hydroxyl group; as a result, no other nucleotide can be added by formation of 3'-5' bonds, which causes chain termination and therefore effective reduction of viral replication.

Both herpes simplex virus species, type 1 and type 2, are highly sensitive to aciclovir.

In severely immunocompromised patients, prolonged or repeated treatment with aciclovir may lead to the selection of viral strains with decreased sensitivity. Consequently, these patients no longer respond to treatment with aciclovir.

Aciclovir penetrates the skin. At steady state, intradermal aciclovir concentrations are above the minimum inhibitory concentration in tissue. Aciclovir is not detectable in the blood after application to the skin. The results reported below concern oral or intravenous administration.

The main metabolite is 9-(carboxymethoxymethyl) guanine. It represents 10 to 15% of the drug excreted renally. The major part of the amount of aciclovir reaching the plasma is eliminated unchanged by the kidneys (both by glomerular filtration and tubular excretion).

The plasma half-life of aciclovir in patients with normal renal function is approximately 3 hours. Plasma protein binding is relatively low (9-33%).

Interactions through displacement from protein binding sites are therefore unlikely.

A large number of in vitro tests have shown that chromosomal damage is possible at very high doses. In in vivo studies, however, no chromosomal damage was observed. Long-term studies in rats and mice did not reveal a carcinogenic effect of aciclovir. In standardised tests according to international standards, systemic administration of aciclovir to different animal species did not produce embryotoxic or teratogenic effects. In a non-standardised test in rats, effects on the foetus were observed only at very high doses that also caused maternal toxicity.

The cream must not be mixed with other products.

3 years.

No special precautions for storage.

No special requirements.