ACTION AND MECHANISM - Antiviral. Acyclovir is a virostatic agent with a structure analogous to guanosine, which inhibits the cellular synthesis of viral DNA. The antiviral effect is only observed in viruses during the replication phase. This selective action is due to the fact that the first phosphorylation of acyclovir to acyclovir monophosphate involves a viral enzyme, thymidine kinase, for which acyclovir has 200 times greater affinity than for the human enzyme. In cells not infected by the virus, this first phosphorylation is very slow. Subsequent phosphorylations to reach the active form of the drug, acyclovir triphosphate, are carried out by cellular enzymes. Acyclovir triphosphate is able to inhibit viral replication through three pathways: * Selective inhibition of viral DNA polymerase. * Competition between acyclovir triphosphate and guanosine triphosphate for incorporation into viral DNA. * Interruption of the chain upon incorporation into viral DNA. It is particularly active against herpes simplex virus (HSV) types 1 and 2, and varicella-zoster virus. In descending order, it also exhibits in vitro activity against Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and cytomegalovirus (CMV). Against CMV (a virus lacking thymidine kinase), its activity is much lower than that of famciclovir or foscarnet. SPECIAL WARNINGS - Treatment should begin as soon as the first symptoms appear. - Patients with severe infection, severe immunosuppression, or frequent recurrences may require oral acyclovir for infection control. - It is recommended to perform a differential diagnosis in young children in the case of a possible first herpes infection, as the symptoms could be confused with other oral or teething disorders. SENIORS No specific problems have been described in the elderly that would require a dosage adjustment. PATIENT ADVICE - Treatment should begin as soon as possible after the onset of symptoms. Acyclovir does not prevent transmission of the virus. Therefore, extra precautions should be taken to reduce the risk of infection, such as avoiding contact of the lesions with hands or other objects, or using condoms in the case of genital herpes. However, genital herpes can still be transmitted to areas not covered by a condom. - Consult your doctor if symptoms worsen or do not improve after using acyclovir for 10 days. - Avoid applying it to eyes or mucous membranes, such as the inside of the mouth or vagina. CONTRAINDICATIONS - Hypersensitivity to acyclovir, valacyclovir or any other component of the medication. EFFECTS ON DRIVING It does not appear to have a significant effect. PREGNANCY Animal safety : no harmful effects have been observed on pregnancy, embryofetal development, parturition or postnatal development. Safety in humans : There are no adequate and well-controlled studies in humans. There is very limited data on use in pregnant women, where no adverse effects on the fetus have been observed. Its administration is only acceptable if there are no safer therapeutic alternatives, and the benefits outweigh the potential risks. Effects on fertility : No specific studies have been conducted in humans via topical administration. Systemic administration did not adversely affect sperm (morphology, motility, count). PHARMACOKINETICS - Absorption: Acyclovir barely penetrates intact skin, reaching undetectable levels (< 0.01 mcg/ml) after administration 4 times a day for 7 days. In the skin of people with herpes zoster, plasma concentrations of 0.01-0.28 mcg/ml are reached. - Distribution: low binding to plasma proteins (9-33%). Its Vd is 0.8 l/kg. - Metabolism: It undergoes partial metabolism by hydroxylation and oxidation reactions. Two metabolites have been described, 8-hydroxy-acyclovir and 9-carboxymethoxy-methyl-guanine, both inactive. Enzyme inducing/inhibiting capacity : does not appear to have significant effects. - Elimination: primarily in urine in unchanged form. After topical administration, between 0.02-9.4% of the dose is recovered in urine in unchanged form. Its CLr is 173-353 ml/min/1.73 m2 and the t1/2 is 2.5-3.3 h. Pharmacokinetics in special situations : - Renal insufficiency: an increase in plasma concentration (Cp) has been observed, with values ​​of 0.78 mcg/ml. However, due to its minimal topical absorption, this is unlikely to be significant. - Other situations: there are no data available on how age or the degree of hepatic function might affect the pharmacokinetics of acyclovir after topical administration. INDICATIONS - Treatment in immunocompetent patients of localized skin infections caused by herpes simplex virus, especially [HERPES SIMPLEX LABIAL] and [HERPES GENITAL] initial and recurrent. INTERACTIONS They have not been described. It is unlikely due to their minimal absorption. LACTATION Animal safety: no data available. Safety in humans: Acyclovir is excreted in breast milk. Following administration of 200 mg five times daily, breast milk concentrations were 0.6–4.1 times the maternal plasma concentration, which would correspond to an infant dose of 0.3 mg/kg/24 h. However, it is estimated that due to its poor cutaneous absorption, breast milk levels would be minimal. Its administration is only acceptable if there are no safer therapeutic alternatives, and the benefits to the mother outweigh the potential risks to the infant. CHILDREN No specific problems have been described in children that would require a dosage adjustment. Use is recommended under medical supervision, especially in children under 12 years of age. Cold sores are a recurrence of an infection inside the mouth that is usually contracted at a young age. A medical diagnosis is recommended for children, as the symptoms of the first infection may go unnoticed or be mistaken for teething problems or other oral conditions. GUIDELINES FOR PROPER ADMINISTRATION Apply to the affected area, gently massaging to promote absorption. It is recommended to use a finger cot or rubber glove to prevent spreading the infection to other parts of the body. If this is not possible, it is advisable to wash your hands before and after application, and to avoid touching the lesions with your hands, towels, or other objects to prevent the infection from worsening or spreading to others. Avoid applying to mucous membranes, such as the mouth, eyes, or vagina, due to the risk of irritation. In case of accidental contact with the eyes, rinse thoroughly with water and consult an ophthalmologist. POSOLOGY - Adults: Apply a thin layer to the lesions 5 times a day, approximately every 4 hours, omitting application during nighttime sleep. For maximum effectiveness, it is important to start treatment as soon as possible, as soon as the first symptoms appear. - Children and adolescents < 18 years: no dosage adjustment required. Perform under medical supervision. - Elderly: no dosage adjustment required. Treatment duration: 5 days. If complete healing has not occurred, extend for another 5 days, for a total of 10 days. If symptoms worsen or do not improve during this period, reassess the diagnosis. Missed dose: Take the next dose at the usual time. Do not double the next dose. DOSAGE IN HEPATIC INSUFFICIENCY No specific dosage recommendations have been made. DOSAGE IN RENAL INSUFFICIENCY No specific dosage recommendations have been made. PRECAUTIONS - [IMMUNODEFICIENCY]. In severely immunocompromised patients, such as those with [HIV INFECTION] or who have undergone [TRANSPLANTATION], topical acyclovir may be insufficient to combat the infection. Oral acyclovir should be considered. ADVERSE REACTIONS Adverse reactions are described according to each frequency interval, being considered very common (>10%), common (1-10%), uncommon (0.1-1%), rare (0.01-0.1%), very rare (<0.01%) or of unknown frequency (cannot be estimated from the available data). - Dermatological: infrequent local reactions in the application area, such as local burning sensation, [PRURITUS], [DRY SKIN], [SKIN SCALING]; rare [ERYTHEMA], [CONTACT DERMATITIS]. - Allergic: very rare [HYPERSENSITIVITY REACTIONS], including [ANGIOEDEMA]. ADVERSE REACTIONS RELATED TO EXCIPIENTS - This medicine contains propylene glycol, so it may cause [SKIN IRRITATION]. OVERDOSE Symptoms: Significant poisoning is unlikely due to the route of administration. No symptoms have been reported following accidental ingestion of 10 g of cream (500 mg of acyclovir). There have been cases of patients receiving up to 20 g orally without experiencing symptoms. Measures to be taken: - Antidote: there is no specific antidote. - General elimination measures: although no action seems necessary, acyclovir is removed by hemodialysis. - Monitoring: patients clinical status. - Treatment: symptomatic.