Valtrex

/ GSK

Dosage in Adults
For treatment of herpes zoster: The dosage in adults is 1000 mg of valaciclovir to be taken three times daily for seven days. No data are available on efficacy of treatment started more than 72 hours after rash onset.
For the treatment of herpes simplex infection (herpes genitalis): 500mg of valaciclovir to be taken twice daily. For recurrent episodes treatment should be 5 days. For initial episodes, which can be more severe, treatment may have to be extended to 10 days. There are no data of the effectiveness of treatment with valaciclovir when initiated more than 24 hours after onset of signs and symptoms. Dosing should begin as early as possible. For recurrent episodes of herpes simplex, this should ideally be during the prodromal period, or immediately as the first signs or symptoms appear. Valaciclovir can prevent lesion development, when taken at the first signs and symptoms of an HSV recurrence.
For the prevention (suppression) of recurrences of herpes simplex (herpes genitalis) in immunocompetent patients: 500 mg of valaciclovir to be taken once daily.
Prophylaxis of cytomegalovirus (CMV) infection and disease:
Adults and adolescents from 12 years of age: The dose is 2g four times daily. Treatment is to be initiated as soon as possible after organ transplantation. The dose should be reduced according to creatinine clearance. The duration of treatment will usually be 90 days, but may be extended in high risk patients.
Cold Sores (Herpes Labialis):
Adults: The recommended dosage of valaciclovir for the treatment of cold sores is 2 grams twice daily for 1 day taken about 12 hours apart. Therapy should be initiated at the earliest symptom of a cold sore (e .g, tingling, itching, or burning). There are no data on the effectiveness of treatment initiated after the development of clinical signs of a cold sore (e.g. , papule, vesicle, or ulcer).
Dosage in children: No data are available.
Dosage in renal impairment: Caution is advised when administering valaciclovir to patients with impaired renal function. Adequate hydration should be maintained.
For full details see prescribing information.

For the treatment of herpes zoster (shingles) in immunocompetent adults. Valtrex accelerates the resolution of pain, reduces the duration, and the proportion of patients with zoster-associated pain, which includes acute and post-herpetic neuralgia. The efficacy in immunocompromised patients has not been established. For the treatment of initial and recurrent genital herpes due to herpes simplex infection.For the prevention (suppression) of recurrent herpes simplex infections (herpes genitalis). Prophylaxis of cytomegalovirus infection and disease, following organ transplantation. For the treatment of cold sores (herpes labialis).

Valaciclovir is contraindicated in patients known to be hypersensitive to valaciclovir, acyclovir or any components of formulations of valaciclovir.

Hydration status: Care should be taken to ensure adequate fluid intake in patients who are at particular risk of dehydration particularly the elderly.
Use in patients with renal impairment and in elderly patients: Aciclovir is eliminated by renal clearance, therefore the dose of valaciclovir must be reduced in patients with renal impairment. Elderly patients are likely to have reduced renal function and therefore the need for dose reduction must be considered in this group of patients. Both elderly patients and patients with renal impairment are at increased risk of developing neurological side effects and should be closely monitored for evidence of these effects. In the reported cases, these reactions were generally reversible on discontinuation of treatment.
Use of high-dose valaciclovir in patients with hepatic impairment or liver transplantation: There are no data available on the use of high doses of valaciclovir ( 4 g or more per day) in patients with liver disease. Caution should therefore be exercised when administering high doses of valaciclovir to these patients. Specific studies of valaciclovir have not been conducted in liver transplantation patients; however high-dose acyclovir prophylaxis has been shown to reduce CMV infection and disease.
Cold sores (Herpes Labialis): patients should be advised to initiate treatment at the earliest symptom of a cold sore (e.g., tingling, itching, or burning ). There are no data on the effectiveness of treatment initiated after the development of clinical signs of a cold sore ( e.g., papule, vesicle, or ulcer). Patients should be instructed that treatment for cold sores should not exceed 1 day ( 2 doses)
and that their doses should be taken about 12 hours apart. Patients should be informed that valaciclovir is not a cure for cold sores (herpes labialis).
Pregnancy and lactation: Should only be used in pregnancy if the potential benefits outweigh the potential risk. Caution is advised in nursing women.

Nervous system disorders: Common: Headache.
Gastrointestinal disorders: Common: Nausea.
Other: There have been reports of renal insufficiency, microangiopathic haemolytic anaemia and  thrombocytopenia (sometimes in combination) in severely immunocompromised patients, particularly those with advanced HIV disease, receiving high doses (8 g daily) of valaciclovir for prolonged periods in clinical trials. These findings have been observed in patients not treated with valaciclovir who have the same underlying or concurrent conditions.
For full details see prescribing information.

No clinically significant interactions have been identified. Acyclovir is eliminated primarily unchanged in the urine via active tubular secretion. Any drugs administered concurrently that compete for this route of elimination may increase plasma acyclovir concentrations following valaciclovir administration. Following 1g valaciclovir, cimetidine and probenecid increase the AUC of acyclovir by this mechanism, and reduce acyclovir renal clearance. However, no dosage adjustment is necessary because of the wide therapeutic index of acyclovir. In patients receiving high-dose valaciclovir (4 g or more/day), for CMV prophylaxis, caution is required during concurrent administration with drugs which compete with acyclovir for elimination, because of the potential for increased plasma levels of one or both drugs or their metabolites. Increases in plasma AUCs of acyclovir and of the inactive metabolite of mycophenolate mofetil, an immunosuppressant agent used in transplant patients, have been shown when the drugs are coadministered. Care is also required (with monitoring for change in renal function) if administering high-dose valaciclovir (4 g or more/day) with drugs which affect other aspects of renal physiology (e.g. cyclosporin, tacrolimus).

Pregnancy: There are limited data on the use of valaciclovir in pregnancy. Valaciclovir should only be used in pregnancy if the potential benefits of treatment outweigh the potential risk.
Pregnancy registries have documented the pregnancy outcomes in women exposed to Valaciclovir or to any formulation of acyclovir, the active metabolite of valaciclovir; 111 and 1246 outcomes (29 and 756 exposed during the first trimester of pregnancy), respectively, were obtained from women prospectively registered. The findings of the acyclovir pregnancy registry have not shown an increase in the number of birth defects amongst acyclovir-exposed subjects compared with the general population, and any birth defects showed no uniqueness or consistent pattern to suggest a common cause. Given the small number of women enrolled into the valaciclovir pregnancy registry, reliable and definitive conclusions could not be reached regarding the safety of valaciclovir in pregnancy.
Lactation: Acyclovir, the principle metabolite of valaciclovir, is excreted in breast milk. Following oral administration of a 500 mg dose of valaciclovir, peak acyclovir concentrations (Cmax) in breast milk ranged from 0.5 to 2.3 (median 1.4) times the corresponding maternal acyclovir serum concentrations. The acyclovir breast milk to maternal serum AUC ratios ranged from 1.4 to 2.6 (median 2.2). The median acyclovir concentration in breast milk was 2.24 g/ml (9.95 M). With a maternal valaciclovir dosage of 500 mg twice daily, this level would expose a nursing infant to a daily oral acyclovir dosage of about 0.61 mg/kg/day. The elimination half-life of acyclovir from breast milk was similar to that for serum. Unchanged valaciclovir was not detected in maternal serum, breast milk, or infant urine.
Caution is advised if valaciclovir is to be administered to a nursing woman. However, acyclovir is used to treat neonatal herpes simplex at intravenous doses of 30 mg/kg/day.

Symptoms and signs: Acute renal failure and neurological symptoms, including confusion, hallucinations, agitation, decreased consciousness and coma, have been reported in patients receiving overdoses of valaciclovir. Nausea and vomiting may also occur. Caution is required to prevent inadvertent overdosing. Many of the reported cases involved renally impaired and elderly patients receiving repeated overdoses, due to lack of appropriate dosage reduction.
Treatment: Patients should be observed closely for signs of toxicity. Haemodialysis significantly enhances the removal of acyclovir from the blood and may, therefore, be considered a management option in the event of symptomatic overdose.