Volrite 500 mg/ 1000 mg TABLETS

VOLIRTE TABLETS is indicated for the treatment of herpes zoster (shingles). VOLIRTE TABLETS reduces the duration of zoster-associated pain, which includes acute and postherpetic neuralgia, thus accelerating resolution of pain. VOLIRTE TABLETS also reduces the proportion of patients with zoster-associated pain. VOLIRTE TABLETS is indicated for the episodic treatment of recurrent genital herpes in immunocompetent adult patients. VOLIRTE TABLETS is indicated for the prevention (suppression) of recurrent herpes simplex infection of the skin and mucous membrane of the ano-genital area. VOLIRTE TABLETS is indicated for the prophylaxis of cytomegalovirus (CMV) infection, CMV disease and other herpes virus infections following organ transplantation, where special risk exists.

Dosage in adults: For the treatment of Herpes Zoster: 1000 mg of VOLIRTE TABLETS to be taken three times per day for seven days. Recurrent genital herpes: The recommended dosage for the treatment of recurrent genital herpes is 500 mg twice daily for 5 days. Dosing should begin as early as possible. For recurrent episodes of herpes simplex, this should ideally be during the prodormal period or immediately the first signs or symptoms appear. There are no data on the effectiveness of VOLIRTE TABLETS when initiated more than 24 hours after the onset of signs and symptoms. For the prevention (suppression) of recurrences of herpes simplex infection: Immunocompetent patients: 500 mg to be taken once daily. Some patients with very frequent recurrences (e.g. 10 or more per year) may gain additional benefit from the daily dose of 500 mg being taken as a divided dose (250 mg twice daily). Immunocompromised patients: 500 mg twice daily. Prophylaxis of cytomegalovirus infection (CMV) and disease: Adults and adolescents (from 12 years of age): 2000 mg to be taken four times a day. Dosing should be initiated as early as possible post-transplant. This dose should be reduced according to creatinine clearance (See Dosage in renal impairment). The duration of treatment will usually be 90 days, but may need to be extended in high risk patients.

VOLIRTE TABLETS is contraindicated in patients known to be hypersensitive to valaciclovir, aciclovir or any component of their formulations. Safety in pregnancy and lactation has not been established. (See u201cPREGNANCY AND LACTATIONu201d).

Thrombotic, thrombocytopenic purpura/haemolytic uraemic syndrome (TTP / HUS): TTP / HUS in some cases resulted in death, has been reported in patients with advanced HIV disease and also in bone marrow transplant and renal transplant recipients. Cases of acute renal failure have been reported in:

• Elderly patients with or without reduced renal function. Caution should be exercised when administering VOLIRTE TABLETS to elderly patients, and dosage reduction is recommended for those with impaired renal function.
• Patients with underlying renal disease who received higher than recommended doses of VOLIRTE TABLETS for their level of renal function. Dosage reduction is recommended when administering VOLIRTE TABLETS to patients with renal impairment.
• Patients receiving other nephrotoxic medicines. Caution should be exercised when administering VOLIRTE TABLETS to patients receiving potentially nephrotoxic medicines.
• Patients without adequate hydration. Precipitation of aciclovir in renal tubules may occur when solubility (2,5 mg/ml) is exceeded in the intratubular fluid. Adequate hydration should be maintained for all patients. In the event of acute renal failure and anuria, the patient may benefit from haemodialysis until renal function is restored.

Central Nervous System (CNS) CNS adverse reactions, including agitation, hallucinations, confusion, delirium, seizures, and encephalopathy, have been reported in both adult and paediatric patients with or without reduced renal function and in patients with underlying renal disease who received higher than recommended doses of VOLIRTE TABLETS for their level of renal function. Elderly patients are more likely to have CNS adverse reactions. VOLIRTE TABLETS should be discontinued if CNS adverse reactions occur.

Effects on ability to drive and use machines: When driving vehicles or using machines it should be taken into account that dizziness or weariness or visual disturbances may occur.

No clinically significant interactions have been identified. Cimetidine and probenecid increase the area under the plasma concentration time curve of aciclovir by reducing its renal clearance: however no dosage adjustment is necessary because of the wide therapeutic index of aciclovir. Other medicines which affect renal physiology could affect plasma levels of aciclovir. In patients receiving high-dose VOLIRTE TABLETS (8 g/day) for CMV prophylaxis, caution is required during concurrent administration with medicines which compete with aciclovir for elimination, because of the potential for increased plasma levels of one or both medicines or their metabolites. Increases in plasma AUCs of aciclovir and of the inactive metabolite of mycophenolate mofetil, an immunosuppressant agent used in transplant patients, have been shown when the medicines are co-administered. Care is also required (with monitoring for changes in renal function) if administering high-dose VOLIRTE TABLETS with medicines which affect other aspects of renal physiology (e.g. cyclosporin, tacrolimus).

Safety in pregnancy and lactation has not been established (see u201cCONTRA-INDICATIONSu201d). Teratogenicity: Foetal abnormalities were observed in rats.

When driving vehicles or using machines it should be taken into account that dizziness or weariness or visual disturbances may occur.

Blood and the lymphatic system disorders: Less Frequent: Aplastic anaemia, Thrombocytopenia, Haemolytic anaemia, micro-angiopathic, neutropenia. Leukocytoclastic vasculitis. Immune system disorders: Less Frequent: Acute hypersensitivity reactions and anaphylaxis and angioedema. Nervous system disorders: Frequent: Headache. Less frequent: Decreased consciousness in patients with renal insufficiency, Dizziness, somnolence, convulsions, Fatigue, Aggressive behaviour, Agitation, Ataxia, coma, confusion, dysarthria, encephalopathy, seizures and tremors. Psychiatric disorders: Less Frequent: Mania and psychosis, including auditory and visual hallucinations. Eye disorders: Less Frequent: Visual abnormalities. Cardiac disorders: Less Frequent: Tachycardia. Vascular disorder: Less Frequent: Hypertension. Gastrointestinal disorders: Frequent: Nausea. Less frequent: Gastrointestinal disturbances such as constipation, diarrhoea, loss of appetite, stomach pain, vomiting. Hepato-biliary disorders: Less frequent: Hepatitis with liver function test abnormalities, jaundice. Skin and subcutaneous tissue disorders: Less Frequent: Facial oedema. Skin reactions such as erythema multiforme, photosensitivity, or rash (redness of the skin). Alopecia, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria, pruritus. Musculoskeletal, connective tissue and bone disorders: Less Frequent: Arthralgia. Renal and urinary disorders: Less Frequent: Renal insufficiency manifested by increased serum creatinine, acute renal failure. Reproductive system and breast disorders: Less Frequent: Dysmenorrhoea.

Symptoms and signs: There are at present no data available on overdose with VOLIRTE TABLETS. In animal studies, large doses caused obstructive uropathy and crystalluria. Management: In the event of asymptomatic VOLIRTE TABLETS overdose occurring, aciclovir is removable by haemodialysis.