Acyclovir

Aciclovir (also known as ACV) is an antiviral drug capable of interfering with the DNA synthesis of viruses.

Acyclovir - Chemical Structure

From the chemical point of view, acyclovir is an analogue of guanosine, one of the nucleosides that constitutes DNA.

Aciclovir is marketed in the form of pharmaceutical formulations suitable for oral, ocular, dermal and intravenous administration.

Indications

For what it uses

The use of aciclovir is indicated for:

• Treatment of skin infections caused by Herpes simplex, including primary and relapsing Herpes genitalis (oral administration);
• Suppression of Herpes simplex recurrences in immunocompetent patients (oral administration);
• Prevention of Herpes simplex infections in immunocompromised patients (oral and intravenous administration);
• Treatment of chicken pox and herpes zoster (oral administration);
• Treatment of Herpes simplex skin infections, including primary or recurrent Herpes genitalis and Herpes labialis (dermal administration);
• Herpes simplex keratitis treatment (ocular administration);
• Treatment of Herpes simplex and Varicella zoster infections in immunocompromised patients (intravenous administration);
• Treatment of recurrent Varicella zoster infections and primary herpes genitalis in immunocompetent patients (intravenous administration);
• Herpes simplex encephalitis (intravenous administration with use restrictions only in hospitals and nursing homes);
• Treatment of Herpes simplex infections in newborns (intravenous administration).

Warnings

In elderly and renally impaired patients, a reduction in the dose of aciclovir usually administered orally and intravenously may be necessary.

In addition, elderly patients and patients with renal insufficiency are exposed to a greater risk of occurrence of side effects affecting the central nervous system, therefore, they must be constantly monitored.

Patients receiving high-dose oral aciclovir should take plenty of fluids to maintain hydration.

Aciclovir can cause side effects that can affect the ability to drive and / or use machinery, so care should be taken.

Interactions

Concomitant administration of oral or intravenous acyclovir and cimetidine (a drug used to reduce acid secretion of the stomach) or probenecid (a drug used to treat gout) may decrease the elimination rate of aciclovir and increase it accordingly, plasma concentration.

In any case - regardless of the type of pharmaceutical formulation based on acyclovir that is used - it is always good to inform your doctor if you are taking, or have recently been, any type of medication, including medicines without a prescription. and herbal and / or homeopathic products.

Side effects

Aciclovir can cause various types of side effects, although not all patients experience them. This is due to the different sensitivity that each individual has towards the drug. Therefore, it is not said that the undesirable effects occur all with the same intensity in each patient.

The following are the main side effects that may occur during acyclovir therapy.

Blood and lymphatic system disorders

Treatment with acyclovir can cause anemia, leukopenia (ie a decrease in the number of leukocytes in the bloodstream) and thrombocytopenia (ie a decrease in the number of platelets in the bloodstream).

Nervous system disorders

Acyclovir therapy may cause:

• Headache;
• Dizziness;
• Tremors;
• Ataxia;
• Dysarthria;
• Drowsiness;
• Encephalopathy;
• Coma.

Psychiatric disorders

Aciclovir treatment can cause agitation, hallucinations, psychotic symptoms and confusion.

Skin and subcutaneous tissue disorders

During acyclovir therapy, the following may occur:

• Skin eruptions;
• Itch;
• Light sensitivity;
• Urticaria;
• Rapid hair loss;
• Skin rash.

Gastrointestinal disorders

Abdominal pain, nausea, vomiting and diarrhea may occur following the administration of aciclovir.

Hepatobiliary disorders

Treatment with aciclovir may cause reversible increases in bilirubin and liver enzymes in the bloodstream, hepatitis and jaundice.

Kidney and urinary tract disorders

Acyclovir therapy may promote the onset of:

• Increased blood levels of urea nitrogen and creatinine;
• Renal pain;
• Acute renal failure.

Other side effects

Other side effects that may occur during treatment with aciclovir are:

• Anaphylaxis;
• Angioedema;
• Dyspnoea;
• Temperature;
• Fatigue;

Furthermore, when acyclovir is administered intravenously, local inflammation and skin ulceration may occur in the event of accidental extravasation into the tissues surrounding the blood vessels in which the drug was administered.

Side effects typical of dermal administration of acyclovir

After the application of the cream or cream for labial use based on aciclovir, undesirable effects may occur, such as:

• Burning or transient pain in the area of ​​application;
• Dryness or peeling of the skin;
• Itch;
• Erythema;
• contact dermatitis;
• Hypersensitivity reactions including angioedema and urticaria.

Side effects typical of ocular administration of acyclovir

Symptoms such as:

• Moderate and transient burning after the application of the ointment;
• Inflammation of the deep layer of the cornea (superficial punctate keratopathy);
• Local irritation and inflammation.

Overdose

In the event of excessive doses of oral acyclovir, gastrointestinal symptoms (such as nausea and vomiting) and neurological symptoms (such as headache and confusion) may occur.

On the other hand, intravenous acyclovir overdose may cause:

• Increased serum creatinine;
• Increased azotemia;
• Kidney failure;
• Confusion;
• Hallucinations;
• agitation;
• Convulsions;
• Coma.

Hemodialysis can be useful to eliminate excess antiviral from the bloodstream.

In any case, if aciclovir overdose is suspected (regardless of the pharmaceutical formulation used), it is necessary to contact the doctor immediately and contact the nearest hospital.

Action mechanism

Aciclovir exerts its antiviral action by interfering with the synthesis of new viral DNA. More in detail, acyclovir succeeds in entering cells that have been infected by the virus and here it undergoes phosphorylation (that is, phosphate groups are added) to become acyclovir triphosphate.

Aciclovir triphosphate has a chemical structure very similar to that of guanosine triphosphate (one of the nucleosides that will then form the new DNA strand). Thanks to this characteristic, acyclovir is incorporated into the viral DNA strand that is being formed instead of guanosine, thus causing an "error" in the growing DNA strand. As a result, due to this error, the elongation and synthesis of the new DNA chain is stopped.

Mode of Use - Posology

Aciclovir is available for:

• Oral administration in the form of tablets, suspension and granules;
• Cutaneous administration in the form of cream and lip cream;
• Ocular administration in the form of an ophthalmic ointment;
• Intravenous administration in the form of a powder for solution for infusion that must be dissolved in a special solvent just before its use.

The following are some indications on the doses of aciclovir usually administered.

Oral administration

The dose of oral acyclovir usually given to adult patients is 200-800 mg of drug, to be taken four to five times a day at 4-6 hour intervals.

The amount of aciclovir to be taken, the frequency of administration and the duration of therapy are established by the doctor, depending on the type of infection to be treated and according to the conditions of the immune system of the patients.

In children over two years of age the dosages used are similar to those used in adults. In children under two years of age, on the other hand, doses usually used are halved compared to those used in adults.

During therapy with aciclovir it is advisable to follow the instructions given by the doctor scrupulously, both as regards the amount of drug to be taken and the duration of the therapy itself.

In patients with severe renal impairment, a lower dose of acyclovir than usual will be given.

Cutaneous administration

Acyclovir cream should be applied to the lesions and areas where they are developing five times a day, with an interval of about four hours between one application and another. Usually, the treatment lasts from five up to a maximum of ten days.

The labial cream is used for the treatment of cold sores. It is recommended to apply it five times a day at intervals of about four hours. The treatment can last from five days up to a maximum of ten.

Ocular administration

For the treatment of herpes simplex keratitis, the acyclovir based ophthalmic ointment is used. The application of the ointment in the inferior conjunctival sac is recommended five times a day, at intervals of about four hours. Therapy should continue for at least three days after recovery.

Intravenous administration

Intravenous administration of acyclovir should be done through a slow drip which should last over an hour.

Depending on the type of infection to be treated, the duration of therapy can be five, ten, fourteen or twenty-one days.

The dose of intravenous acyclovir usually given to adults is 5-10 mg / kg of body weight every eight hours. The amount of drug administered varies according to the infection to be treated.

In children, the dose usually administered is 250-500 mg / m2 of body surface every eight hours, depending on the infection to be treated.

In neonates with suspected or ascertained neonatal herpes, the dose of acyclovir usually used is 20 mg / kg of body weight every eight hours.

In elderly patients and patients with renal impairment, the dose of intravenous acyclovir administered will be lower than the doses usually used.

Pregnancy and breastfeeding

The use of aciclovir by pregnant women and by breastfeeding mothers is generally contraindicated.

The use of aciclovir by this category of patients should only be considered in cases of absolute necessity and only if the potential benefits expected for the mother outweigh the potential risks to the fetus or newborn. However, any administration of the antiviral should only take place under strict medical supervision.

In any case, pregnant women and breastfeeding mothers should always seek medical advice before taking any type of medication.

Contraindications

The use of aciclovir is contraindicated in the following cases:

• In patients with known hypersensitivity to aciclovir;
• In patients with known hypersensitivity to valaciclovir (the prodrug of aciclovir);
• Pregnant;
• During breastfeeding.