Valacyclovir - Usage, Indications, Contraindications, and Side Effects

Overview

Aciclovir is the active antiviral component of Valacyclovir (also spelled Valaciclovir). Valacyclovir is chemically a valyl ester of aciclovir. The prodrug of aciclovir (L-valyl ester of aciclovir) undergoes first-pass metabolism, and Aciclovir is yielded along with an essential amino acid named L-valine. Valacyclovir and aciclovir are nucleoside analogs. An active antiviral component has been identified in drugs like Aciclovir and Valacyclovir in various laboratory tests and experiments. Valacyclovir is considered the drug of choice for immunocompetent patients. The drug Valacyclovir significantly reduces the duration of Zoster-associated pain. Valacyclovir is a well-tolerated drug and has very few adverse effects associated with it. The Food and Drug Administration (FDA) approved the drug Valacyclovir on June 15, 2001. Valacyclovir is used to treat herpes zoster infections, chickenpox, herpes labialis, and genital herpes.

Uses of the Drug Valacyclovir

Valacyclovir is an antiviral medication. It is used to treat viral infections caused by the herpes virus. Herpes zoster (shingles) in adults, genital herpes; cold sores in children around twelve years of age, and chicken pox in children around two years of age. Valacyclovir cannot prevent the spread of viral infection, but it can reduce the symptoms of herpes virus infection. Therefore, a Valacyclovir treatment regimen should be initiated as soon as the initial symptoms like tingling, burning, and blisters start to appear.

Dosage and Administration

The dosage of this drug varies from patient to patient, and it is also modified on the basis of the type of lesion that is being treated. Following are the drug dosage and the type of lesion being treated:

Chicken Pox:

• Children aged 2 to 18 - 20 mg/kg body weight of Valacyclovir is given three times a day for five days. The dose should not increase more than 1000 mg three times a day.

• Dosage for children below two years of age is decided by the doctor on the basis of the severity of the lesion and the child's build.

Cold Sores:

• Adults - 2000 mg every 12 hours for one day.

• For children aged 12 years and above - 2000 mg every 12 hours for one day.

• Dosage for children below two years of age is decided by the doctor on the basis of the severity of the lesion and the child's body weight.

Genital Herpes:

• Adults - 1000 mg two times a day for ten days.

• The dosage for children is decided by the doctor on the basis of the severity of the lesion and the child's build.

Recurrent Genital Herpes:

• Adults - 500mg 0r 1000 mg once a day.

• The dosage for children is decided by the doctor on the basis of the severity of the lesion and the child's build.

Shingles:

• 1000 mg three times a day for seven days.

• The dosage for children is decided by the doctor on the basis of the severity of the lesion and the child's build.

Dosage Forms and Strengths

Valacyclovir is available in tablet forms ranging from 400mg, 500mg, and 1000mg.

Dosage and Modifications

• In patients suffering from renal impairment, proper hydration should be maintained, and the doctors must prescribe the dosage of the drug accordingly.

• In immunocompromised patients with creatinine levels less than 30ml/min, the dosage for the drug Valacyclovir should be around 500mg per day.

• In immunocompetent patients, the dosage of the drug is adjusted accordingly.

• In immunocompromised patients with creatinine levels less than 30ml/min, the dosage for the drug Valacyclovir should be around 250mg per day.

What Are the Contraindications of Valacyclovir?

It is contraindicated in patients with the following conditions:

• Allergy: Allergy to the drug Valacyclovir, as allergic patients may show symptoms of hypersensitivity reactions like angioedema (swelling affecting the tissue below the mucous membrane), anaphylaxis (acute allergic reaction), or exfoliative skin diseases(severe inflammation affecting the entire skin surface).

• Alcohol intake: A well-established report is not yet published regarding the interaction of alcohol with Valacyclovir, but it is contraindicated as it can worsen drowsiness and dizziness symptoms.

What Are the Warnings and Precautions of Valacyclovir?

Heart Failure:

Peramivir has been documented to worsen the symptoms of heart failure in patients suffering from myocarditis. Following are a few of the features of heart failure that should be noted in these patients:

• Shortness of breath during exercising or while doing any other physical activity, shortness of breath can also be present at rest in individuals suffering from heart failure.

• Fatigue and weakness are commonly noted, and the individual gets tired while performing basic day-to-day activities.

• Swellings in the legs, ankles, and feet are an important indicator of heart failure due to electrolyte imbalance in these individuals.

• Irregular heartbeat.

• Persistent cough and wheezing with whitish or pinkish-tinged mucus are also commonly noted in these individuals.

Hypersensitivity:

Clinical trials have reported a few cases of urticaria (extensively itchy rashes caused due to an allergic reaction), facial edema (swelling of the face), and exfoliative skin disease associated with individuals. Therefore, the medication should be immediately discontinued in individuals with severe hypersensitivity symptoms, and emergency management protocols should be followed. Alternative drugs should be prescribed when an allergic reaction to Valacyclovir gets established to protect the individual from the life-threatening hypersensitivity reactions associated with Valacyclovir.

Neuropsychiatric Events:

Hallucinations, delirium, and abnormal behavior are commonly noted neurological symptoms associated with drug usage. Few cases have been reported showing such symptoms. It is always advisable to closely monitor the signs of abnormal behavior in these patients.

Renal Impairment:

In patients suffering from renal impairment, proper hydration should be maintained, and the doctors must prescribe the dosage of that drug accordingly.

What Are the Drug Interactions of Valacyclovir?

• No serious drug interactions of Valacyclovir have been noted with other drugs, but a few cases of severe drug interactions include the influenza virus vaccine.

• Aspirin should not be prescribed for relieving fever as Valacyclovir can interact with the drug and lead to the development of Reye's syndrome (the central nervous system and liver are involved in these individuals, and children can have symptoms like vomiting, drowsiness, and behavioral changes). It is always advisable not to stop or change the dosage of any medicine without reporting it to their doctor.

Adverse Reactions Associated With Valacyclovir

Adverse reactions include unexpected or dangerous reactions associated with a particular drug. Following are a few commonly associated adverse reactions with Valacyclovir:

• Stevens-Johnson syndrome, exfoliative dermatitis, and rashes are noted as hypersensitivity reactions with the drug valacyclovir. The medication should be immediately discontinued in individuals with severe hypersensitivity symptoms, and emergency management protocols should be followed. Alternative drugs should be prescribed when an allergic reaction to Valacyclovir gets established to protect the individual from the life-threatening hypersensitivity reactions associated with Valacyclovir.

• Hallucinations, delirium, and abnormal behavior are commonly noted neurological symptoms associated. Few studies state that these are rare symptoms. Doctor’s should closely monitor the abnormal signs in these patients.

For Patients

What Is Herpes Virus Infection?

The Herpes virus belongs to the herpes viridae family. These groups of viruses cause contagious infections in humans. In a few patients, recurrent viral infections are also commonly noted, and they also undergo periodic reactivation. It can cause severe complications in immunocompromised hosts.

• Herpes simplex virus-1 causes infections in the orofacial region as well as encephalitis.

• Herpes simplex virus-2 causes genital infections that can be transferred from the mother to the child during pregnancy.

These viruses are noted to stay in the sensory neurons, get reactivated, and cause recurrent infections under suitable conditions. Around 60%-90% of human adults get affected by this disorder. The highest incidence of herpes simplex virus-1 infection occurs between the ages of six months to three years. The primary infection of herpes simplex virus-2 infection is commonly noted in young adults. Transmission of the Herpes simplex virus is commonly associated with direct contact and through saliva.

Following are a few common signs and symptoms of Herpes Simplex virus infection:

• Chills and high fever.

• Vesicles in the oral cavity associated with Herpes simplex virus one infection.

• Vesicles in the genital area associated with herpes simplex virus -2 infection.

• Sore throat.

• Dry cough.

• Muscle aches.

• Fatigue.

• Diarrhea.

• Dizziness.

• Malaise.

Herpes simplex virus infection can be diagnosed using the following diagnostic tests:

• Viral isolation from nasopharyngeal secretion samples.

• Indirect fluorescent antibody detection tests.

What Is Valacyclovir?

The active antiviral component of valacyclovir is Aciclovir. The prodrug of acyclovir (L-valyl ester of aciclovir)undergoes first-pass metabolism, and aciclovir is yielded along with an essential amino acid named L-valine.Valacyclovir is an antiviral medication. It is prescribed for treating viral infections caused by the herpes virus. Herpes zoster (shingles) is caused in adults, genital herpes; cold sores, and chicken pox in children around two years of age. For treating immunocompetent patients Valacyclovir is considered the Drug of choice.Valacyclovir significantly reduces the duration of pain associated with herpes Zoster infection. Valacyclovir is a well-tolerated drug and has very few adverse effects associated with it.

What Is to Be Done in the Case of a Missed Dose and an Overdose of Valacyclovir?

• Missed Dose: In case the individual forgets to take the prescribed dose, or in any case, the amount is omitted, then the tablet should be taken as soon as they remember, or if it is time for the second dose, then the individual can skip the missed dose and immediately continue with the next prescribed dose.

• Overdose: In case of overdose, the individual may have symptoms like nausea, vomiting, dizziness, or pain in the stomach. If this happens, the patient should be immediately taken to the hospital, and a thorough check up should be done. In severe toxicity, gastric lavage is given, and the patient is kept under medical supervision.

For Doctors

Pharmacology

The L-valyl ester of acyclovir undergoes first-pass metabolism, and aciclovir is yielded as the result of the metabolism along with an essential amino acid named L-valine. Valacyclovir and aciclovir are chemically nucleoside analogs.

Drug Toxicity

• Neurological symptoms are noted to be associated with drug valacyclovir that includes hallucinations, delirium, and abnormal behavior.

• urticaria (extensively itchy rashes caused due to an allergic reaction), facial edema (swelling of the face), and exfoliative skin disease.

• Fatigue and weakness is also noted in many cases.

• Stevens-Johnson syndrome, exfoliative dermatitis, and rashes are noted as hypersensitivity reactions with the drug valacyclovir.

Drug Interactions

• No serious drug interactions of Valacyclovir have been recorded in medical literature till date.Drug interactions with the influenza virus vaccine were noted to be serious and life threatening .

• Valacyclovir is an antiviral drug and during viral infections patients suffer from high fever. Doctors must make a note that Aspirin should not be prescribed for relieving fever as Valacyclovir can interact with the drug and lead to the development of Reye's syndrome (the central nervous system and liver are involved in these individuals, and children can have symptoms like vomiting, drowsiness, and behavioral changes). Reye’s syndrome is a serious complication noted in children. Doctors must look for such symptoms and prescribe the drug accordingly.

Mechanism of Action

Valacyclovir is converted into acyclovir by the action of valacyclovir hydrolase. Thymidine kinase is the enzyme responsible for the first stage of drug phosphorylation. Cellular kinases complete the phosphorylation steps.

The antiviral effects of valacyclovir are achieved in 3 ways:

• Viral DNA polymerase is competitively inhibited.

• Termination of the growing viral DNA chain.

• Inactivation of the viral DNA polymerase.

Absorption:

Valacyclovir is rapidly absorbed by the gastrointestinal tract. Therefore, the bioavailability of Aciclovir is not affected by food intake.

Protein Binding:

Human plasma protein binding of the drug valacyclovir is noted to be less than 13.5% to 17.9%.

Route of Elimination:

The urine excretes 89% of the drug. Radioactive tests have marked the excretion of this drug in urine.

The half-life of the Drug:

The half-life of this drug is around 2.5 to 3.3 hours.