Posology : מינונים

4.2     Posology and method of administration
Varicella zoster virus (VZV) infections – herpes zoster and ophthalmic 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 1000 mg three times daily for seven days (3000 mg total daily dose). This dose should be reduced according to creatinine clearance (see Renal impairment below).

Immunocompromised Adults
The dose in immunocompromised patients is 1000 mg three times daily for at least seven days (3000 mg total daily dose) and for 2 days following crusting of lesions. This dose should be reduced according to creatinine clearance (see Renal impairment below).

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 (≥12 years)
The dose is 500 mg of Valtrex to be taken twice daily (1000 mg total daily dose).
This dose should be reduced according to creatinine clearance (see Renal impairment below).

For recurrent episodes, treatment should be for three to five days. For initial episodes, which can be more severe, treatment may have to be extended to ten 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. Valtrex can prevent lesion development, when taken at the first signs and symptoms of an HSV recurrence.

Herpes labialis
For herpes labialis (cold sores), valaciclovir 2000 mg 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 (see Renal impairment below).
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
For the treatment of HSV in immunocompromised adults, the dosage is 1000 mg 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 (see Renal impairment below). 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 500 mg of Valtrex 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 500 mg being taken as a divided dose (250 mg twice daily). This dose should be reduced according to creatinine clearance (see Renal impairment below).Treatment should be re-evaluated after 6 to 12 months of therapy.

Immunocompromised Adults

The dose is 500 mg of Valtrex twice daily. This dose should be reduced according to creatinine clearance (see Renal impairment below). 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 Valtrex is 2000 mg four times a day, to be initiated as early as possible post-transplant.
This dose should be reduced according to creatinine clearance (see Renal impairment below).
The duration of treatment will usually be 90 days, but may need to be extended in high-risk patients.

Special populations

Elderly
The possibility of renal impairment in the elderly must be considered and the dose should be adjusted accordingly (see Renal impairment below). Adequate hydration should be maintained.

Renal impairment
Caution is advised when administering Valtrex to patients with impaired renal function. Adequate hydration should be maintained. The dose of Valtrex should be reduced in patients with impaired renal function as shown in Table 1 below.
In patients on intermittent haemodialysis, the Valtrex dose should be administered after the haemodialysis has been performed.

The creatinine clearance should be monitored frequently, especially during periods when renal function is changing rapidly e.g. immediately after renal transplantation or engraftment. The Valtrex dosage should be adjusted accordingly.

Hepatic impairment
Studies with a 1000 mg dose of valaciclovir in adult patients show that dose modification is not required in patients with mild or moderate cirrhosis (hepatic synthetic function maintained). Pharmacokinetic data in adult patients with advanced cirrhosis, (impaired hepatic synthetic function and evidence of portal-systemic shunting) do not indicate the need for dose adjustment; however, clinical experience is limited. For higher doses (4000 mg or more per day), see section 4.4.


Table 1:       DOSAGE ADJUSTMENT FOR RENAL IMPAIRMENT
Creatinine
Valaciclovir
Therapeutic Indication                        Clearance
Dosage a
(mL/min)
Varicella-Zoster Virus (VZV) Infections
Treatment of herpes zoster (shingles)     ≥ 50                     1000 mg three times daily in immunocompetent and                    30 to 49                 1000 mg twice daily immunocompromised adults                  10 to 29                 1000 mg once daily 10                       500 mg once daily
Herpes Simplex Virus (HSV) Infections
Treatment of HSV infections
- immunocompetent adults and         ≥ 30                     500 mg twice daily adolescents                          < 30                     500 mg once daily ≥ 30                     1000 mg twice daily
- immunocompromised adults
< 30                     1000 mg once daily
Treatment of herpes labialis (cold        ≥50                      2000mg twice in one day sores) in immunocompetent adults and      30 to 49                 1000 mg twice in one day adolescents                               10 to 29                 500 mg twice in one day (alternative 1-day regimen)               <10                      500 mg single dose Suppression of HSV infections

- immunocompetent adults and         ≥ 30                     500 mg once daily b adolescents                          < 30                     250 mg once daily ≥ 30                     500 mg twice daily
- immunocompromised adults
< 30                     500 mg once daily
Cytomegalovirus (CMV) Infections
CMV prophylaxis in solid organ            ≥75                     2000 mg four times daily transplant recipients in adults and       50 to <75               1500 mg four times daily adolescents                               25 to <50               1500 mg three times daily 10 to <25               1500 mg twice daily
<10 or on dialysis      1500 mg once daily a
For patients on intermittent haemodialysis, the dose should be given after dialysis on dialysis days.
b
For HSV suppression in immunocompetent subjects with a history of ≥10 recurrences/year, better results may be obtained with 250 mg twice daily.


Paediatric populations
The safety and efficacy of Valtrex in children below the age of 12 years has not been established.