Valacyclovir is used for the treatment of herpes zoster (shingles) and ophthalmic zoster in immunocompetent adults. It is also used to treat herpes zoster in adults with mild or moderate immunosuppression.

Herpes simplex virus (HSV) infections : Valacyclovir is indicated for the treatment and suppression of HSV infections of the skin and mucous membranes, including:

• Treatment of the first episode of genital herpes in immunocompetent adults and adolescents, and in immunocompromised adults
• Treatment of recurrent genital herpes in immunocompetent adults and adolescents, and in immunocompromised adults
• Suppression of recurrent genital herpes in immunocompetent adults and adolescents, and in immunocompromised adults
• Treatment and suppression of recurrent ocular HSV infections

Cytomegalovirus (CMV) infections : Valacyclovir is used for the prevention of CMV infection and disease following solid organ transplantation in adults and adolescents.

Valacyclovir is the hydrochloride salt of the L-valyl ester of the antiviral drug acyclovir. It is an antiviral medication that slows down the growth and spread of the herpes virus, allowing the body’s immune system to fight the infection. Valacyclovir helps reduce the symptoms of infection and shortens the duration of illness. It is used for the treatment and suppression of genital herpes, shingles, and cold sores.

Varicella zoster virus (VZV) infections- herpes zoster: Patients should be advised to start treatment as soon as possible after a diagnosis of herpes zoster. There are no data on treatment started more than 72 hours after onset of the zoster rash. Immunocompetent Adults: The dose in immunocompetent patients is Valacyclovir 1000mg (1 Valacyclovir 1000mg tablet) three times daily for 7 days (3000mg total daily dose).

Immunocompromised Adults: The dose in immunocompromised patients is Valacyclovir 1000mg (1 Valacyclovir 1000mg tablet) 3 times daily for at least 7 days (3000mg total daily dose) and for 2 days following crusting of lesions. In immunocompromised patients, antiviral treatment is suggested for patients presenting within one week of vesicle formation or at any time before full crusting of lesions.

Treatment of herpes simplex virus (HSV) infections in adults and adolescents (>12 years): Immunocompetent Adults and Adolescents (³12 years): The dose is Valacyclovir 500mg (1 Valacyclovir 500mg tablet) to be taken twice daily (1000mg total daily dose). This dose should be reduced according to creatinine clearance. For recurrent episodes, treatment should be for 3 to 5 days. For initial episodes, which can be more severe, treatment may have to be extended to 10 days. Dosing should begin as early as possible. For recurrent episodes of herpes simplex, this should ideally be during the prodromal period or immediately upon appearance of the first signs or symptoms. Valacyclovir can prevent lesion development when taken at the first signs and symptoms of an HSV recurrence.

Herpes labialis: For herpes labialis (cold sores), Valacyclovir 2000mg (2 Valacyclovir 1000mg tablet) twice daily for one day is effective treatment in adults and adolescents. The second dose should be taken about 12 h (no sooner than 6 h) after the first dose. This dose should be reduced according to creatinine clearance. When using this dosing regimen, treatment should not exceed one day, since this has been shown not to provide additional clinical benefit. Therapy should be initiated at the earliest symptom of a cold sore (e.g. tingling, itching or burning).

Immunocompromised Adults: The dosage is Valacyclovir 1000mg (1 Valacyclovir 1000mg tablet) twice daily for at least 5 days, following assessment of the severity of the clinical condition and immunological status of the patient. For initial episodes, which can be more severe, treatment may have to be extended to ten days. Dosing should begin as early as possible. This dose should be reduced according to creatinine clearance. For maximum clinical benefit, the treatment should be started within 48 hours. A strict monitoring of the evolution of lesions is advised.Suppression of recurrences of herpes simplex virus (HSV) infections in adults and adolescents (12 years)

Immunocompetent Adults and Adolescents (12 years): The dose is Valacyclovir 500mg (1 Valacyclovir 500mg tablet) to be taken once daily. Some patients with very frequent recurrences (10/year in absence of therapy) may gain additional benefit from the daily dose of Valacyclovir 500mg (1 Valacyclovir 500mg tablet) being taken as a divided dose (250mg twice daily). Treatment should be re-evaluated after 6 to 12 months of therapy.

Immunocompromised Adults: The dose is Valacyclovir 500mg (1 Valacyclovir 500mg tablet) twice daily. Treatment should be re-evaluated after 6 to 12 months of therapy. Prophylaxis of cytomegalovirus (CMV) infection and disease in adults and adolescents (12 years) The dosage of Valacyclovir is 2000mg (2 Valacyclovir 1000 mg tablet) four times a day, to be initiated as early as possible post-transplant. This dose should be reduced according to creatinine clearance.The duration of treatment will usually be 90 days, but may need to be extended in high-risk patients.

Valacyclovir should be used with caution when combined with nephrotoxic medicines, especially in patients with impaired kidney function. In such cases, regular monitoring of renal function is recommended. This precaution applies when Valacyclovir is taken together with medicines such as aminoglycosides, organoplatinum compounds, iodinated contrast media, methotrexate, pentamidine, foscarnet, ciclosporin, and tacrolimus. Acyclovir, the active form of Valacyclovir, is mainly eliminated unchanged in the urine through active renal tubular secretion. After taking Valacyclovir 1000 mg, medicines such as cimetidine and probenecid can reduce the renal clearance of acyclovir and increase its exposure in the body. Cimetidine may increase the acyclovir AUC by about 25 percent and probenecid by about 45 percent. When both are taken together with Valacyclovir, the acyclovir AUC may increase by about 65 percent. Other medicines that compete with or inhibit active tubular secretion, such as tenofovir, may also increase acyclovir concentrations. Likewise, Valacyclovir may increase the plasma levels of other drugs that are eliminated through the same pathway. Patients receiving higher exposure to acyclovir from Valacyclovir should use caution when taking medicines that inhibit renal tubular secretion. Co-administration with mycophenolate mofetil may increase the plasma exposure of acyclovir and its inactive metabolite. However, studies in healthy volunteers showed no significant change in peak levels or overall exposure when Valacyclovir and mycophenolate mofetil were taken together. Clinical experience with this combination is still limited.

Valacyclovir is contraindicated in patients who have known hypersensitivity or allergic reactions to Valacyclovir, aciclovir, or to any of the other ingredients present in the formulation.

The most frequently reported adverse effects in at least one clinical indication among patients treated with Valacyclovir are headache and nausea. Additional side effects include: Blood and lymphatic system disorders such as leucopenia and thrombocytopenia, with leucopenia being more common in immunocompromised individuals. Immune system disorders include anaphylaxis. Psychiatric and nervous system disorders may present as dizziness, confusion, hallucinations, reduced concentration, tremor, agitation, ataxia, dysarthria, convulsions, encephalopathy, coma, and psychotic manifestations. Respiratory disorders include dyspnea. Gastrointestinal disorders include vomiting, diarrhea, and abdominal discomfort. Hepatobiliary disorders may involve reversible elevations in liver function tests. Skin and subcutaneous tissue disorders include rashes, photosensitivity, pruritus, and urticaria. Renal system disorders include renal pain and renal impairment, particularly in elderly patients or those receiving doses higher than recommended; renal pain may be associated with renal failure.

Available data on the use of Valacyclovir and a moderate amount of information on aciclovir use during pregnancy, derived from pregnancy registries and postmarketing experience, do not indicate any risk of congenital malformations or fetal/neonatal toxicity. Animal studies have not demonstrated reproductive toxicity with Valacyclovir. Valacyclovir should be prescribed during pregnancy only if the expected therapeutic benefits outweigh the potential risks. During lactation, aciclovir—the primary metabolite of Valacyclovir—is excreted into breast milk. However, at therapeutic doses of Valacyclovir, no adverse effects are expected in breastfed infants, as the amount ingested is less than 2% of the intravenous therapeutic dose used for neonatal herpes. Valacyclovir should be used cautiously during breastfeeding and only when clearly indicated.

Hydration status: Patients, especially elderly individuals or those at risk of dehydration, should maintain adequate fluid intake while taking Valacyclovir.

Use in patients with renal impairment and in elderly patients: Acyclovir, the active metabolite of Valacyclovir, is eliminated mainly through the kidneys. Therefore, the dose of Valacyclovir should be reduced in patients with impaired kidney function. Elderly patients are more likely to have reduced renal function, so dose adjustment may be necessary. Both elderly patients and those with kidney problems have a higher risk of developing neurological side effects and should be carefully monitored. In most reported cases, these effects were reversible after discontinuation of the medication.

Use of higher doses in hepatic impairment and liver transplantation: There is limited information on the use of high doses of Valacyclovir (4000 mg or more per day) in patients with liver disease. Specific studies in liver transplant patients have not been conducted. Therefore, caution should be taken when administering daily doses greater than 4000 mg to these patients.

Use in herpes zoster treatment: Clinical response should be carefully monitored, especially in immunocompromised patients. If oral treatment is not effective enough, intravenous antiviral therapy should be considered. Patients with complicated herpes zoster, such as those with internal organ involvement, widespread infection, motor neuropathy, encephalitis, or cerebrovascular complications, may require intravenous antiviral treatment. Immunocompromised patients with ophthalmic zoster or those at high risk of disease spread should also receive intravenous antiviral therapy.

Transmission of genital herpes: Patients should be advised to avoid sexual intercourse when symptoms are present, even if antiviral treatment has already started.

Use in ocular HSV infections: Patients with ocular herpes simplex virus infections should be closely monitored. If oral therapy is not expected to be sufficient, intravenous antiviral treatment may be required.

Use in CMV infections: In transplant patients who are at high risk of cytomegalovirus infection, Valacyclovir should generally be used only when other treatments such as valganciclovir or ganciclovir cannot be used for safety reasons. High doses of Valacyclovir used for CMV prevention may increase the risk of side effects compared to lower doses used for other conditions. Patients should be closely monitored for kidney function changes, and dose adjustments should be made if necessary.

Overdose of Valacyclovir may lead to serious complications such as acute kidney failure and neurological symptoms. Reported symptoms include confusion, hallucinations, agitation, decreased level of consciousness, and coma. Nausea and vomiting may also occur. Care should be taken to avoid accidental overdose. Many reported cases of overdose occurred in elderly patients or in patients with kidney impairment who received repeated doses without proper dose adjustment. Patients who receive an excessive amount of Valacyclovir should be closely monitored for signs of toxicity. Hemodialysis can significantly help remove aciclovir from the blood and may be considered as a treatment option in cases of symptomatic overdose.

Herpes simplex & Varicella-zoster virus infections

Store Valacyclovir in a cool and dry place. Keep it away from direct heat, light, and out of the reach of children.