INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo LOVIRE 200 Tablets
LOVIRE 400 Tablets
LOVIRE 800 Tablets

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

LOVIRE 200 Tablets
LOVIRE 400 Tablets
LOVIRE 800 Tablets

COMPOSITION
Lovire 200 tablets: Each dispersible tablet contains
Aciclovir 200 mg
Lovire 400 tablets: Each dispersible tablet contains Aciclovir 400 mg
Lovire 800 tablets: Each dispersible tablet contains Aciclovir 800 mg

PHARMACOLOGICAL CLASSIFICATION
A 20.2.8 Antiviral agents

PHARMACOLOGICAL ACTION
Mode of Action
Aciclovir is an antiviral agent with activity against Herpes simplex virus types 1 and 2, (HSV-1 and HSV-2) and varicella zoster virus (VZV). Aciclovir is phosphorylated after entry into herpes infected cells to the active compound aciclovir triphosphate. The first step in this process is dependent on the presence of the HSV coded thymidine kinase. Thymidine kinase converts aciclovir into aciclovir monophosphate. The monophosphate is further converted to diphosphate by cellular guanylate kinase and to triphosphate which is the active form of the medicine. Aciclovir triphosphate interferes with HSV and VZV DNA polymerase and inhibits viral DNA replication.
Pharmacokinetics
When given orally, 15-30% of aciclovir is absorbed from the gastrointestinal tract. The absorption of aciclovir is not significantly altered when administered after a meal. The mean steady-state peak concentrations after repeated oral administration of aciclovir 200 mg, and 400 mg have been reported to be 0,6 and 1,2 mcg/mL respectively. With repeated administration of 800 mg of aciclovir, a steady state plasma concentration of 1,6 mcg/mL has been reported Aciclovir is bound to plasma proteins up to an extent of 9 to 33%.
Aciclovir is predominantly eliminated unchanged by glomerular filtration and tubular secretion. The terminal elimination half life of aciclovir is about 2-3 hours in subjects with normal renal function; this may increase to 20 hours in patients with severely compromised renal function. About 15% of the administered dose is recovered in the urine as an inactive metabolite (9-carboxy methoxy methyl guanine) and about 2% is excreted with the faeces.

INDICATIONS
- Treatment of initial and recurrent Herpes simplex infections of the skin and mucous membranes.
- Treatment of initial and recurrent Herpes genitalis infections in immunocompromised and non-immunocompromised patients.
- Prophylaxis of Herpes simplex infections in immunocompromised patients.
- Prophylaxis against recurrent (>6 episodes per year) Herpes genitalis infections in HIV-infected patients and patients receiving cancer chemotherapy or immunosuppressive therapy.
- Treatment and prophylaxis of Herpes zoster infections including treatment of Herpes zoster ophthalmicus. Treatment is effective if started within 48 hours of onset of rash.
- Treatment of chicken pox especially in those at increased risk of severe infection or complications such as children over 12 months of age with a chronic cutaneous or pulmonary disorder, or children receiving corticosteroids. Oral aciclovir is effective in the treatment of varicella zoster infections if started within 24 hours of onset of rash.

CONTRA-INDICATIONS
Aciclovir is contra-indicated in patients hypersensitive to aciclovir or ganciclovir. In patients with pre-existing impairment of renal function, neurological abnormalities or dehydration, the potential risks and benefit should be carefully considered. The safety in pregnancy and lactation has not been established.

WARNINGS
Impairment of renal function can occur in patients on aciclovir therapy.

DOSAGE AND DIRECTIONS FOR USE
Usual Adult Dose
Genital Herpes infections
Initial infection: 200 mg orally, five times a day for ten days.
Recurrent infections: 200 mg orally, five times a day for five days.
Chronic suppressive therapy (for prophylaxis against recurrent genital Herpes): 400 mg orally, twice a day or 200 mg orally, three to five times a day.
Herpes Zoster: 800 mg orally, five times a day for seven to ten days.
Varicella (treatment): 800 mg orally, four times a day for five days.
To be started within 24 hours of onset of rash.

Dose adjustment in renal impairment
Indicators Creatinine
Clearance
(mL/min)
        Dose
        (mg)
Dosing Interval
        (hr)
Genital Herpes
Initial/intermittent
therapy
        >10
        0-10
        200
        200
4 (5 times daily)
        12
Chronic suppressive
therapy
        >10
        0-10
        400
        200
        12
        12
Herpes zoster:         >25
        10-25
        0-10
        800
        800
        800
4 (5 times daily)
        8
        12
Directions for use:
Aciclovir tablets may be taken with meals since absorption has not been shown to be significantly affected by food. As it may take longer for lesions of Herpes simplex to heal in immunocompromised patients, the duration of therapy may need to be prolonged beyond the recommended period until the lesions are crusted over or epithelialized. The tablets must be dispersed in 50 mL of water or swallowed whole.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS
Adverse effects reported include gastrointestinal disturbances and headache.
Alteration in values of bilirubin and liver related enzymes, blood urea and creatinine & megaloblastic haemopoiesis has also been reported in patients receiving aciclovir.
Oral administration of aciclovir for long term (6-12 months) or at high doses, is associated with nausea, vomiting, diarrhoea, abdominal pain, headache, rash and light headedness.
Although acute renal insufficiency is most likely to occur if aciclovir is given by rapid intravenous injection, concomitantly with other nephrotoxic agents in patients with compromised renal function without any dosage reduction, it has also been reported in patients receiving oral aciclovir. Alteration in value of hepaticenzygus and megaloblastic haemopoiesis also has been reported.
Neuropsychiatric toxicity (confusion, hallucinations, tremors, seizures and coma) can occur if doses are not adjusted in patients with impaired renal function or in immunocompromised or geriatric patients.
Precautions
Cross-sensitivity
Patients allergic to ganciclovir may also be allergic to aciclovir.
Renal insufficiency
Aciclovir should be administered with caution to patients with renal impairment and doses should be adjusted according to creatinine clearance.
Paediatrics
No unusual toxicity has been observed in studies done in children using doses up to 80 mg/kg/day. In children older than 2 years of age the pharmacokinetics of aciclovir is similar to that seen in adults with normal renal function.
Geriatrics
Due to age related decrease in renal function, geriatric patients may require adjustment of dosage. (Please refer to “Dosage in renal impairment”).
Interactions
Probenecid decreases the renal tubular secretion of aciclovir leading to increased concentration in serum, prolonged half life and increased toxicity.
Nephrotoxic agents like paracetamol, aminoglycosides, amphotericin B, lithium, methotrexate and methoxyflurane may increase the potential for nephrotoxicity of aciclovir when concurrently administered.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
See side effects and special precautions. Hemodialysis decreases plasma aciclovir concentration, especially in patients with acute renal failure and anuria. Treatment is symptomatic and supportive.

IDENTIFICATION
Lovire 200 Tablets
Capsule shaped, biconvex, uncoated white to off-white tablets with ‘200’embossed on one side and ‘ACV’on the other side.
Lovire 400 tablets
Capsule shaped, biconvex, uncoated white to off-white tablets with ‘400’embossed on one side and ‘ACV’on the other side.
Lovire 800 Tablets
Capsule shaped, biconvex, uncoated white to off-white tablets with ‘800’embossed on one side and ‘ACV’on the other side.

PRESENTATION
Lovire 200 Tablets:         Carton containing 25 tablets in blister strips.
Lovire 400 Tablets:         Carton containing 56 or 70 tablets in blister strips.
Lovire 800 Tablets:         Carton containing 35 tablets in blister strips.

STORAGE INSTRUCTIONS
Store below 25°C, protected from moisture.
KEEP OUT OF REACH OF CHILDREN

REGISTRATION NUMBERS
Lovire 200 Tablets:        32/20.2.8/0017
Lovire 400 Tablets:        32/20.2.8/0018
Lovire 800 Tablets:        32/20.2.8/0019

NAME AND BUSINESS ADDRESS OF APPLICANT:
RANBAXY (SA) (PTY) LTD.
Lincoln House
Epsom Downs Office Park
13 Sloane Street
Epsom Downs
BRYANSTON

DATE OF PUBLICATION OF THIS PACKAGE INSERT
January 1998

KLTL002

Updated on this site: January 2000

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