Description

Acyclovir (Zovirax)

Mechanism of action

An antiviral drug that inhibits the replication of herpes type 1 and 2 viruses (HSV), weaker chickenpox and shingles virus (VZV), Epstein and Barr virus (EBV) and cytomegalovirus (CMV). Acyclovir is a synthetic purine nucleotide analogue with an acyclic side chain. In infected cells, it is phosphorylated to active acyclovir triphosphate, which inhibits DNA synthesis in two ways: it inhibits the incorporation of deoxyguanosine triphosphate into viral DNA and is incorporated into the replicating viral DNA chain (DNA polymerase mistakenly recognizes acyclovir triphosphate) as triphosphate phosphate. It does not affect host cell metabolism because the affinity of viral thymidine kinase for acyclovir is several hundred times greater than that of host cell kinases. Long-term administration of acyclovir or repeated treatment cycles in patients with severely compromised immunity may result in the selection of viral strains with reduced susceptibility to the drug. Most isolated strains with reduced sensitivity show relative thymidine kinase deficiency, however strains with altered viral thymidine kinase or DNA polymerase have also been described.

Pharmacokinetics
15-20% is absorbed from the gastrointestinal tract. Administered after a dose of 0.2-0.4 g every 4 h attains average concentration of 0.7 and 1.2 mg / ml; after iv administration at a dose of 5 mg / kg or 10 mg / kg the mean concentration is 9.8 or 20.7 mg / ml, respectively. t1 / 2 in the blood is 3.3 hours after administration after and 2.9 hours after iv administration. Plasma protein binding is 15-30%, penetrates into organs, reaching a significant concentration in the liver, kidneys, muscles, lungs and penetrates into female milk. The concentration in the cerebrospinal fluid is 30-50% of the concentration in the blood. It is excreted mainly in the urine. After topical application to the conjunctival sac, it reaches therapeutic concentration in the intraocular fluid.

Infections caused by the herpes simplex virus

Solution for infusion. The drug in the form of a solution for infusion is indicated for the treatment and prevention of infections caused by herpes simplex virus in immunocompromised persons, treatment of severe herpes genital infection in patients with normal immunity and infections caused by the herpes simplex virus of newborns and infants up to 3 m., for the treatment of varicella and herpes zoster infections in patients with normal or impaired immunity, and for the treatment of herpes encephalitis.

Pills. The drug in the form of tablets is indicated for the treatment of skin and mucosal infections caused by herpes simplex virus, including herpes genital infections (except for infections in newborns and severe infections in children with significant immunodeficiency), in preventing the recurrence of herpes infection common in people with normal immunity, in the prevention of infections caused by the herpes simplex virus in people with impaired immunity, and in the treatment of infections caused by the varicella and zoster virus. The drug in the form of eye ointments is indicated for the treatment of herpetic keratitis.

Cream . The drug in the form of a cream is indicated for the local treatment of recurrent herpes of the skin (lips, face, genitals) caused by the herpes simplex virus.

Hypersensitivity to acyclovir, valaciclovir or any of the other ingredients.

Renal failure, the elderly
Use with caution in people with renal failure and in the elderly; patients should be carefully monitored because of the increased risk of CNS side effects. In the event of renal insufficiency, the dose should be reduced accordingly.

High doses
Caution should be exercised in patients receiving high doses of acyclovir – adequate hydration should be ensured.

Rapid iv
injection. Aciclovir must not be administered by rapid iv injection as it may damage the kidneys due to an increased risk of renal crystallisation.

CNS disorders
Infused with aciclovir may cause CNS disorders; caution should be exercised in persons who developed neurological disorders during previous administration of the drug and in persons at risk of developing such disorders: patients with renal or hepatic insufficiency, with significant electrolyte disturbances and significantly hypoxia, and concomitantly treated intrathecally with methotrexate or interferon.

Thymidine kinase.
Decreased activity of viral thymidine kinase may lead to lower efficacy of acyclovir, e.g. when iv acyclovir is used in patients with severe immune deficiency as well as after bone marrow transplantation.

Shingles
Currently available data from clinical trials are not sufficient to conclude that acyclovir treatment reduces the possibility of herpes zoster complications in patients with normal immunity.

Virus susceptibility to treatment
Prolonged administration of acyclovir or repeated courses of treatment in patients with significantly weakened immunity may result in the selection of virus strains with reduced susceptibility to the drug.

pH The
infusion solution should not be administered after , im , sc , topically or into the eye because of high pH = 11.

Additional ingredients of the preparation
Lactose containing drug forms should not be used in people with rare hereditary problems of galactose intolerance, primary lactase deficiency or glucose-galactose malabsorption.
Because the cream medicine may contain paraffin or petroleum jelly, use on the genitals and anal area may reduce the latex condom tear resistance.

Probenecid, cimetidine.
Aciclovir is mainly excreted in the urine through active secretion in the renal tubules; Medicines excreted in the same mechanism (e.g. probenecid, cimetidine) may increase acyclovir blood levels. Due to the high therapeutic index of acyclovir, there is no need to reduce its doses.

Mycophenolate mofetil
Caution should be exercised when IV infusion is given concurrently with medicinal products that compete for excretion due to the potential for increased plasma levels. Increases in acyclovir and the inactive metabolite mycophenolate mofetil have been observed during co-administration, but this is probably not of clinical relevance.

Ciclosporin, tacrolimus
Caution should be exercised and renal function monitored when using aciclovir iv with medicinal products that affect renal function (cyclosporine, tacrolimus).

Zidovudine.
Concomitant use with zidovudine may cause disturbance of consciousness.

Additional information