Aciclin - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Unwanted Effects Shelf Life and Storage Other Information

Active ingredients: Aciclovir

ACICLIN 200, 400, 800 mg tablets
ACICLIN 8% oral suspension
ACICLIN 800 mg granules for oral suspension

Indications Why is Aciclin used? What is it for?

PHARMACOTHERAPEUTIC CATEGORY

Tablets, oral suspension and granules: Antivirals for systemic use.

Cream: topical chemotherapy, antivirals

THERAPEUTIC INDICATIONS

Aciclovir is indicated:

Tablets, oral suspension and granules for oral suspension

  • for the treatment of Herpes Simplex infections of the skin and mucous membranes, including primary and relapsing herpes genitalis;
  • for the suppression of Herpes Simplex relapses in immunocompetent patients;
  • for the prophylaxis of Herpes Simplex infections in immunocompromised patients;
  • for the treatment of chickenpox and herpes zoster.

Cream

  • for the treatment of Herpes Simplex skin infections such as primary or recurrent Herpes genitalis and Herpes labialis.

Contraindications When Aciclin should not be used

Aciclovir tablets and suspension are contraindicated in patients with known hypersensitivity to aciclovir and valaciclovir or to any of the excipients.

Cream:

Aciclovir cream is contraindicated in patients with known hypersensitivity to aciclovir, valaciclovir, propylene glycol or to any of the excipients of aciclovir cream. Generally contraindicated in pregnancy and lactation (see SPECIAL WARNINGS).

Precautions for use What you need to know before taking Aciclin

Children, Elderly, Patients with specific clinical pictures See "DOSE, METHOD AND TIME OF ADMINISTRATION".

Interactions Which drugs or foods can modify the effect of Aciclin

Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.

Tablets, suspension and granules:

No clinically significant interactions have been identified. Aciclovir is excreted primarily unchanged in the urine via active renal tubular secretion. Any concomitantly administered drug that competes with this mechanism of action may increase the plasma concentrations of aciclovir. Probenecid and cimetidine increase the area under the curve for aciclovir through this mechanism, and reduce the renal clearance of aciclovir. Increases in the area under the curve in plasma concentrations of aciclovir and the inactive metabolite of mofetil have been shown. mycophenolate, an immunosuppressive substance used in transplant patients, when these drugs are co-administered. However, no dosage adjustments are necessary due to the broad therapeutic index of aciclovir.

Cream:

No clinically significant interactions have been identified.

Warnings It is important to know that:

Pregnancy

Ask your doctor or pharmacist for advice before taking any medicine.

Tablets, suspension and granules:

Since clinical data on administration in pregnancy are limited, during this period the drug should only be administered in cases of absolute necessity under direct medical supervision, when the potential benefits outweigh the possibility of unknown risks.

Cream:

The use of aciclovir should only be considered if the potential benefits outweigh the possibility of unknown risks, however the systemic exposure of aciclovir following topical application of aciclovir cream is very low.

A registry of post-marketing use of aciclovir in pregnancy provided data on pregnancy outcomes in women exposed to the various aciclovir formulations.

These observations did not show an increase in the number of birth defects among acyclovir-exposed subjects compared to the general population, and all birth defects found did not show any particularities or common characteristics that would suggest a single cause.

Systemic administration of Aciclovir in internationally accepted standard tests did not produce embryotoxic or teratogenic effects in rabbits, rats or mice.

In a non-standard rat test, fetal abnormalities were observed after subcutaneous doses of Aciclovir so high that they produced toxic effects on the mother. The clinical relevance of these findings is uncertain.

Feeding time

Tablets, suspension and granules:

Following oral administration of Aciclovir 200 mg, 5 times / day, the presence of Aciclovir in breast milk was observed at concentrations equal to 0.6-4.1 times the corresponding plasma levels. Such levels would potentially expose infants to Aciclovir doses up to 0.3 mg / kg / day. Therefore, the use of Aciclovir during breastfeeding should be avoided.

Cream:

Limited data indicate that the drug is found in breast milk following systemic administration. However, the dose received by an infant following the use of aciclovir cream in the mother should be insignificant.

Important information about some of the excipients

Due to the presence of aspartame, the granules formulation for oral suspension is not indicated in patients with phenylketonuria.

Each sachet of granules for oral suspension contains 1.8 g of sucrose and therefore this formulation is not suitable for subjects with hereditary fructose intolerance, glucose and galactose malabsorption syndrome or sucrase-isomaltase deficiency.

The oral suspension formulation contains glycerol: harmful in high doses; it can cause migraines, stomach upset and diarrhea.

A 10 ml dose of oral suspension contains not less than 2.6 g of sorbitol and therefore this formulation is not suitable for subjects with hereditary fructose intolerance; it can cause stomach upset and diarrhea.

Tablets, suspension and granules: Use in patients with renal insufficiency and elderly patients

Aciclovir is eliminated by renal clearance, therefore the dose should be reduced in patients with renal insufficiency (see Dose, method and time of administration). Elderly patients are likely to have impaired renal function and therefore the need for dose reduction should be considered in this patient group. Both elderly patients and patients with renal insufficiency are at increased risk of developing neurological side effects and should be carefully monitored for these effects. In reported reports, these reactions were generally reversible upon discontinuation of treatment (see Undesirable Effects). Prolonged or repeated courses of aciclovir in severely immunocompromised patients may be associated with the selection of viral strains with reduced sensitivity, which may not respond to continued aciclovir treatment. Hydration status: Ensure adequate hydration is maintained in patients taking high doses of oral aciclovir.

Cream

The product is not for ophthalmic use, nor is it recommended for application on mucous membranes, such as in the mouth, eye or vagina, as it can cause irritation. Particular care should be taken to avoid accidental application to the eye. In severely immunocompromised patients (eg AIDS patients or bone marrow transplant patients) administration of aciclovir in oral formulations should be considered. It should be recommended that such patients be consult your doctor about the treatment of any infection.

Important information about some of the excipients

The propylene glycol excipient can cause skin irritation.

Effects on ability to drive and use machines

The clinical condition of the patient and the adverse event profile of aciclovir should be taken into account with regard to the patient's ability to drive and use machines. No studies have been performed to investigate the effects of aciclovir on the ability to drive and operate machinery. Further harmful effects on these activities cannot be predicted from the pharmacology of the active ingredient.

Dosage and method of use How to use Aciclin: Dosage

Tablets, suspension and granules

A measuring cup with indicated level marks corresponding to the capacity of 5 and 10 ml is attached to the package of Aciclovir in suspension.

Shake the suspension before use.

Granules: dissolve the contents of one sachet in half a glass of water and shake the suspension.

Adults

Treatment of Herpes Simplex infections

One 200 mg tablet 5 times a day, at intervals of approximately 4 hours, omitting the night dose. Treatment should be continued for 5 days, but prolongation may be necessary in cases of severe primary infections.

In patients with severely impaired immune function (eg, after a bone marrow transplant) or in patients with impaired intestinal absorption, the dosage can be doubled to 400 mg or 5 ml suspension, or alternatively, the appropriateness of to use an intravenous injectable formulation of Aciclovir.

Therapy should be started as soon as possible, and in the case of recurrent infections, preferably at the first symptoms or when the first lesions appear.

Suppressive therapy of relapse of Herpes Simplex infections in patients with normal immune function

One 200 mg tablet 4 times a day, at 6 hour intervals. Many patients can be successfully treated by administering 400 mg tablets or 5 ml suspension twice daily, at 12 hour intervals. Dosages of 200 mg 3 times a day, at 8-hour intervals, or 2 times a day at 12-hour intervals, may also be effective. Relapses of infection may occur in some patients with a total daily dose of 800 mg of ACICLOVIR.

Therapy should be interrupted periodically at intervals of 6 to 12 months, in order to observe any changes in the natural history of the disease.

Prophylaxis of Herpes Simplex infections in patients with impaired immune function

One 200 mg tablet 4 times a day, at 6 hour intervals. In patients with severely impaired immune function (for example, after a bone marrow transplant) or in patients with impaired intestinal absorption, the dosage can be doubled to 400 mg in tablets or 5 ml suspension, or alternatively, it can be evaluated. the opportunity to use an intravenous injectable formulation of Aciclovir.

The duration of prophylaxis must be considered in relation to that of the risk period.

Treatment of Herpes Zoster infections and chickenpox

Schedule of intake throughout the day ˜ hour time of day ˜ 7 Breakfast ˜ 11 late morning ˜ 15 early afternoon ˜ 19 late afternoon ˜ 23 evening

800 mg (1 tablet or 1 sachet or 10 ml suspension) 5 times a day, at intervals of approximately 4 hours, omitting the night dose.

Treatment should be continued for 7 days. In patients with impaired immune function (eg after a bone marrow transplant) or in patients with impaired intestinal absorption, intravenous administration of injectable aciclovir may be considered. "infection, in fact the treatment obtains better results if established at the appearance of the first lesions.

Children

For the treatment of Herpes Simplex infections and for their prophylaxis in immunocompromised children over 2 years of age, the dosage is similar to that of adults. Under 2 years the dosage is reduced by half.

For the treatment of chickenpox in children over 6 years of age, the dosage is 800 mg (1 tablet or 1 sachet or 10 ml suspension) 4 times a day; in those aged between 2-6 years the dosage is 400 mg in tablets or 5 ml of suspension 4 times a day; in those younger than 2 years the recommended dosage is 200 mg (2.5 ml of suspension) 4 times a day.

The administration of 20 mg / kg of body weight (not exceeding 800 mg) 4 times a day, allows a more precise dosage adjustment. Treatment should be continued for 5 days.

No specific data are available on the suppression of Herpes simplex infections or the treatment of Herpes Zoster in children with normal immune function.

For the treatment of Herpes Zoster in children with impaired immune function, consideration should be given to using an intravenous formulation of Aciclovir for injection.

Senior citizens

In the elderly, the total elimination of Aciclovir decreases with decreasing certain renal function indices associated with advancing age. In patients taking high doses of Aciclovir orally, adequate fluid intake should be maintained. Particular attention should be paid to evaluating the possibility of a reduction in dosage in the case of elderly patients with impaired renal function.

Subjects with renal impairment

In the treatment of Herpes simplex infections, in patients with severe renal impairment (creatinine clearance less than 10 ml / min), it is recommended to adjust the dose to: - 200 mg, administered twice daily at approximately 12 hour intervals. In the treatment of chickenpox and herpes zoster, it is recommended that the dosage be changed to:

Creatinine clearance Dose 10 - 25 ml / min 800 mg (moderate renal impairment) 800 mg (1 tablet or 1 sachet or 10 ml suspension) administered 3 times a day, at intervals of approximately 8 hours less than 10 ml / min (severe renal impairment) 800 mg (1 tablet or 1 sachet or 10 ml suspension) administered in layers 2 times a day, at intervals of approximately 12 hours

Cream

Aciclovir cream should be applied 5 times a day, at intervals of approximately 4 hours. Aciclovir cream should be applied to lesions, or areas where they are developing, as early as possible after the infection begins. It is especially important to start treatment for recurrent episodes during the prodrome phase or at the first appearance of lesions. Treatment must continue for at least 5 days and up to a maximum of 10 if there is no healing.

Overdose What to do if you have taken an overdose of Aciclin

In case of accidental ingestion / intake of an excessive dose of ACICLIN, notify your doctor immediately or go to the nearest hospital.

If you have any questions about the use of ACICLIN, ask your doctor or pharmacist.

Tablets, suspension and granules:

Signs and symptoms

Aciclovir is only partially absorbed from the intestine. Patients who have ingested an overdose of up to 20 g of aciclovir in a single dose have generally not experienced toxic effects.

Accidental and repeated overdoses of oral aciclovir over several days have been associated with gastrointestinal effects (such as nausea and vomiting) and neurological effects (headache and confusion).

Overdose of intravenous aciclovir resulted in increased serum creatinine, blood urea nitrogen and subsequent renal failure. Neurological effects including confusion, hallucinations, agitation, convulsions and coma have been reported in conjunction with overdose.

Treatment

Patients should be carefully observed for any signs of toxicity.

Hemodialysis significantly increases the elimination of aciclovir from the blood can therefore be considered an option in the management of drug overdose.

Cream: Even if the entire contents of a tube of cream containing 500 mg of acyclovir are ingested, no undesirable effects should be expected.

Side Effects What are the side effects of Aciclin

Like all medicines, this can cause side effects, although not everybody gets them.

Tablets, suspension and granules

The frequency categories associated with the adverse events listed below are estimates. Adequate incidence assessment data are not available for most events. In addition, the incidence of adverse events may vary by indication.

The following convention has been used for the classification of undesirable effects in terms of frequency: very common ≥ 1/10, common ≥ 1/100 and <1/10, uncommon ≥ 1 / 1,000 and <1/100, rare ≥ 1 /10,000 and <1 / 1,000, very rare <1 / 10,000.

Disorders of the blood and lymphatic system

Very rare: anemia, leukopenia, thrombocytopenia.

Disorders of the immune system

Rare: anaphylaxis.

Psychiatric disorders and pathologies of the nervous system

Common headache, dizziness.

Very rare: agitation, confusion, tremor, ataxia, dysarthria, hallucinations, psychotic symptoms, convulsions, somnolence, encephalopathy, coma.

The above events are generally reversible and usually occur in patients with renal insufficiency or other predisposing factors.

Respiratory, thoracic and mediastinal disorders

Rare: dyspnoea.

Gastrointestinal disorders

Common: nausea, vomiting, diarrhea, abdominal pain.

Hepatobiliary disorders

Rare: reversible increases in bilirubin and liver enzymes.

Very rare: hepatitis, jaundice.

Skin and subcutaneous tissue disorders

Common: pruritus, rash (including photosensitivity).

Uncommon: urticaria. Rapid and widespread hair loss.

Skin rashes occurred in some patients after oral administration of aciclovir and promptly disappeared upon discontinuation of therapy.

Rapid and widespread hair loss has been associated with a "wide range of conditions and drug use," so the relationship of this occurrence to acyclovir therapy is uncertain.

Rare: angioedema.

Renal and urinary disorders

Rare: increases in blood levels of urea nitrogen and creatinine.

Very rare: acute renal failure, renal pain. Kidney pain can be associated with kidney failure.

General disorders and administration site conditions

Common: fatigue, fever.

Cream

The following convention has been used for the classification of undesirable effects in terms of frequency: very common 1/10, common 1/100 and <1/10, uncommon 1 / 1,000 and <1/100, rare 1 / 10,000 and ≥ ≥ ≥ ≥ <1 / 1,000, very rare <1 / 10,000.

Skin and subcutaneous tissue disorders

Uncommon: transient burning or pain after application of aciclovir cream moderate dryness or peeling of the skin itching

Rare: erythema. Contact dermatitis after application. Where sensitivity tests were conducted, it was shown that the substances that gave phenomena of reactivity were the components of the base cream rather than acyclovir.

Disorders of the immune system

Very rare: immediate hypersensitivity reactions including angioedema and urticaria.

Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please inform your doctor or pharmacist.

Expiry and Retention

Check the expiration date indicated on the package.

The expiry date refers to the product in intact packaging, correctly stored.

WARNING: DO NOT USE THE MEDICINAL PRODUCT AFTER THAT DATE.

Conservation rules:

  • 800 mg tablets: store away from moisture.
  • 5% cream: do not store above 25 ° C.

Keep this medicine out of the reach of children.

Deadline "> Other information

COMPOSITION

ACICLIN 200 mg - Tablets

One tablet contains:

  • Active ingredient: 200 mg of Aciclovir
  • Excipients: Lactose; Microcrystalline cellulose; Starch and sodium glycolate; Polyvinylpyrrolidone; Magnesium stearate.

ACICLIN 400 mg - Tablets

One tablet contains:

  • Active ingredient: 400 mg of Aciclovir
  • Excipients: microcrystalline cellulose; Starch and sodium glycolate; Polyvinylpyrrolidone; Magnesium stearate.

ACICLIN 800 mg - Tablets

One tablet contains:

  • Active ingredient: 800 mg of Aciclovir
  • Excipients: microcrystalline cellulose; Starch and sodium glycolate; Polyvinylpyrrolidone; Magnesium stearate.

ACICLIN 8% - Oral suspension

5 ml of oral suspension contains:

  • Active ingredient: 400 mg of Aciclovir
  • Excipients: Sorbitol not crystallizable; Glycerol; Pulverized cellulose; Methyl p-hydroxybenzoate; Propyl p-hydroxybenzoate; Black cherry flavor; Purified water.

ACICLIN 800 mg - Granules for oral suspension

One sachet contains:

  • Active ingredient: 800 mg of Aciclovir
  • Excipients: Lactose; Carboxymethylcellulose; Aspartame; Strawberry flavor; Sucrose.

ACICLIN 5% - Cream

1 g of cream contains:

  • Active ingredient: 50 mg of Aciclovir
  • Excipients: Tefose 1500, Glycerin; Stearic acid; Liquid paraffin; Methylparaben; Purified water as required at 1 g.

PHARMACEUTICAL FORM AND CONTENT

Tablets of 200 mg, 400 mg - box of 25 tablets in blister.

800 mg tablets - box of 35 tablets in blister packs.

Oral suspension 8% - 100 ml bottle with measuring cup.

800 mg granules for oral suspension - box of 35 sachets of 3 g.

5% cream - 10g tube.

Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.

Further information on Aciclin is available in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT - 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION - 03.0 PHARMACEUTICAL FORM - 04.0 CLINICAL PARTICULARS - 04.1 Therapeutic indications - 04.2 Posology and method of administration - 04.3 Contraindications - 04.4 Special warnings and appropriate precautions for use - 04.5 Interactions with other medicinal products and other forms of interaction - 04.6 Pregnancy and lactation - 04.7 Effects on the ability to drive and use machines - 04.8 Undesirable effects - 04.9 Overdose - 05.0 PHARMACOLOGICAL PROPERTIES - 05.1 "Pharmacodynamic properties - 05.2 Pharmacokinetic properties" - 05.3 Preclinical safety data - 06.0 PHARMACEUTICAL PARTICULARS - 06.1 Excipients - 06.2 Incompatibility "- 06.3 Shelf life" - 06.4 Special precautions for storage - 06.5 Nature of the primary packaging and contents of the package - 06.6 Instructions for use and handling - 07.0 AUTHORIZATION HOLDER ALL "PLACING ON THE MARKET - 08.0 MARKETING AUTHORIZATION NUMBER - 09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION - 10.0 DATE OF REVISION OF THE TEXT - 11.0 FOR RADIO DRUGS, COMPLETE DATA ON INTERNAL RADIATION DOSIMETRY - 12.0 INSTRUCTIONS FOR RADIOPHONES ON EXTEMPORARY PREPARATION AND QUALITY CONTROL -

01.0 NAME OF THE MEDICINAL PRODUCT -

ACICLIN

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -

Aciclin 200 mg Tablets

One tablet contains:

Active ingredient: Aciclovir 200 mg

Aciclin 400 mg Tablets

One tablet contains:

Active ingredient: Aciclovir 400 mg

Aciclin 800 mg Tablets

One tablet contains:

Active ingredient: Aciclovir 800 mg

Aciclin 400mg / 5ml Oral suspension

5 ml of suspension contain:

Active ingredient: Aciclovir 400 mg

Aciclin 800 mg Granules for oral suspension

1 sachet of 3 g contains:

Active ingredient: Aciclovir 800 mg

Aciclin 5% Cream

1 g of cream contains:

Active ingredient: Aciclovir 50 mg

For excipients see 6.1

03.0 PHARMACEUTICAL FORM -

Tablets, oral suspension, granules for oral suspension, cream

04.0 CLINICAL INFORMATION -

04.1 Therapeutic indications -

Aciclovir is indicated:

Tablets, oral suspension and granules for oral suspension

- for the treatment of Herpes Simplex infections of the skin and mucous membranes, including primary and relapsing Herpes Genitalis;

- for the suppression of Herpes Simplex relapses in immunocompetent patients;

- for the prophylaxis of Herpes Simplex infections in immunocompromised patients;

- for the treatment of chickenpox and herpes zoster

Cream

- for the treatment of Herpes Simplex skin infections such as: primary or recurrent herpes genitalis and herpes labialis.

04.2 Posology and method of administration -

A measuring cup with level marks corresponding to the capacities of 5 and 10 ml is attached to the package of Aciclin oral suspension.

Treatment of Herpes Simplex infections in adults

200 mg 5 times a day, at intervals of approximately 4 hours, omitting the night dose.

Treatment should be continued for 5 days, but prolongation may be necessary in cases of severe primary infections.

In patients with severely impaired immune function (for example, after a bone marrow transplant) or in patients with impaired intestinal absorption, the dosage can be doubled to 400 mg in tablets or 5 ml suspension, or alternatively, the dose can be evaluated. "opportunity to use an intravenous injectable formulation of Aciclovir.

Therapy should be started as soon as possible, and in the case of recurrent infections, preferably at the first symptoms or when the first lesions appear.

Suppressive therapy of relapses of Herpes Simplex infections in immunocompetent patients

200 mg 4 times a day, at 6 hour intervals.

Many patients can be successfully treated by administering 400 mg tablets or 5 ml suspension twice a day, at 12 hour intervals.

Dosages of 200 mg 3 times a day, at 8-hour intervals, or 2 times a day at 12-hour intervals, may also be effective.

Relapses of infection may occur in some patients with a total daily dose of 800 mg of Aciclovir.

Therapy should be interrupted periodically at intervals of 6 to 12 months, in order to observe any changes in the natural history of the disease.

Prophylaxis of Herpes Simplex infections in immunocompromised patients

200 mg 4 times a day, at 6 hour intervals. In patients with severely impaired immune function (for example, after a bone marrow transplant) or in patients with impaired intestinal absorption, the dosage can be doubled to 400 mg in tablets or 5 ml suspension, or alternatively, it can be evaluated. the opportunity to use an intravenous injectable formulation of Aciclovir.

The duration of prophylaxis must be considered in relation to that of the risk period.

Treatment of Herpes Zoster infections and chickenpox

800 mg (1 tablet or 1 sachet or 10 ml suspension) 5 times a day, at intervals of approximately 4 hours, omitting the night dose. Treatment should be continued for 7 days.

In severely immunocompromised patients (eg after bone marrow transplantation) or in patients with impaired intestinal absorption, intravenous administration of injectable aciclovir may be considered.

The therapy must be started immediately after the onset of the infection, in fact the treatment obtains better results if established when the first lesions appear.

Children

For the treatment of Herpes Simplex infections and for their prophylaxis in the immunocompromised; in children over 2 years of age, the dosage is similar to that of adults, under 2 years the dosage is reduced by half.

For the treatment of chickenpox in children over 6 years of age, the dosage is 800 mg (1 tablet or 1 sachet or 10 ml suspension) 4 times a day; in those aged between 2-6 years the dosage is 400 mg in tablets or 5 ml of suspension 4 times a day; in those younger than 2 years the recommended dosage is 200 mg (2.5 ml of suspension) 4 times a day. The administration of 20 mg / kg of body weight (not exceeding 800 mg) 4 times a day, allows a more precise dosage adjustment. Treatment should be continued for 5 days.

No specific data are available on the suppression of Herpes Simplex infections or the treatment of Herpes Zoster in children with normal immune function.

For the treatment of Herpes Zoster in children with impaired immune function, consideration should be given to using an intravenous formulation of Aciclovir for injection.

Senior citizens

In the elderly, total clearance decreases with decreasing creatinine clearance associated with advancing age. Adequate hydration should be maintained in patients taking high doses of oral aciclovir. Particular attention should be paid to evaluating the possibility of a reduction in dosage in the case of elderly patients with impaired renal function.

Kidney failure

In the treatment of Herpes Simplex infections, in patients with impaired renal function, the recommended oral dosage should not cause Aciclovir to accumulate above the levels deemed acceptable for intravenous drug administration. However, in patients with severe renal insufficiency (creatinine clearance less than 10 ml / min), it is recommended to adjust the dose to 200 mg administered twice daily at approximately 12 hour intervals.

In the treatment of chickenpox and herpes zoster, it is recommended that the dosage be changed to 800 mg (1 tablet or 1 sachet or 10 ml suspension), administered twice daily at approximately 12 hour intervals, in patients with severe renal impairment. (creatinine clearance less than 10 ml / min) and 800 mg (1 tablet or 1 sachet or 10 ml suspension) 3 times a day, administered at intervals of approximately 8 hours, in patients with moderate renal impairment (creatinine clearance between 10 and 25 ml / min).

Cream

Aciclovir cream should be applied 5 times a day, at intervals of approximately 4 hours.

Aciclovir cream should be applied to lesions, or areas where they are developing, as early as possible after the infection begins. It is especially important to start treatment for recurrent episodes during the prodrome phase or at the first appearance of lesions. Treatment must continue for at least 5 days and up to a maximum of 10 if there is no healing.

04.3 Contraindications -

Aciclovir tablets and suspension are contraindicated in patients with known hypersensitivity to aciclovir and valaciclovir or to any of the excipients.

Cream :

Aciclovir cream is contraindicated in patients with known hypersensitivity to aciclovir, valaciclovir, propylene glycol or to any of the excipients of aciclovir cream.

Generally contraindicated in pregnancy and lactation (see section 4.6).

04.4 Special warnings and appropriate precautions for use -

Children, Elderly, Patients with specific clinical pictures: see "Posology and method of administration".

Due to the presence of aspartame, the formulation granules for oral suspension it is not indicated in patients with phenylketonuria.

Each sachet of granules for oral suspension contains 1.8 g of sucrose and therefore this formulation is not suitable for subjects with hereditary fructose intolerance, glucose and galactose malabsorption syndrome or sucrase-isomaltase deficiency.

The wording oral suspension contains glycerol: harmful in high doses; it can cause migraines, stomach upset and diarrhea.

A 10 ml dose of oral suspension it contains 2.6 g of sorbitol and therefore this formulation is not suitable for subjects with hereditary fructose intolerance; it can cause stomach upset and diarrhea.

Shake the suspension before use.

Tablets, suspension and granules:

Use in patients with renal insufficiency and elderly patients:

Aciclovir is eliminated by renal clearance, therefore the dose should be reduced in patients with renal insufficiency (see section 4.2). Elderly patients are likely to have impaired renal function and therefore the need for dose reduction in this patient group should be considered. Both elderly patients and patients with renal insufficiency have an increased risk of developing neurological side effects and should be carefully monitored for these effects. In reported reports these reactions were generally reversible upon discontinuation of treatment (see section 4.8).

Prolonged or repeated courses of aciclovir in severely immunocompromised patients may lead to a selection of viral strains with reduced sensitivity, which may not respond to continuous courses of aciclovir treatment (see section 5.1).

Hydration Status: Ensure adequate hydration is maintained in patients taking high doses of oral aciclovir.

Cream

The product is not for ophthalmic use, nor is it recommended for application on mucous membranes, such as in the mouth, eye or vagina, as it can cause irritation. Particular care should be taken to avoid accidental application into the eye.

In severely immunocompromised patients (e.g. AIDS patients or bone marrow transplant patients) administration of aciclovir in oral formulations should be considered. Such patients should be recommended to consult their physician regarding the treatment of any infection.

The propylene glycol excipient can cause skin irritation.

Animal studies indicate that the application of Aciclovir cream into the vagina may cause reversible irritation.

The use of the product, especially if prolonged, can give rise to sensitization phenomena, where this happens it is necessary to stop the treatment and consult the attending physician.

04.5 Interactions with other medicinal products and other forms of interaction -

Tablets, suspension and granules:

No clinically significant interactions have been identified.

Aciclovir is excreted primarily unchanged in the urine via active renal tubular secretion. Any concomitantly administered drug that competes with this mechanism of action may increase the plasma concentrations of aciclovir. Probenecid and cimetidine increase the area under the curve for aciclovir through this mechanism, and reduce the renal clearance of aciclovir. Increases in the area under the curve in plasma concentrations of aciclovir and the inactive metabolite of mofetil have been shown. mycophenolate, an immunosuppressive substance used in transplant patients, when these drugs are co-administered. However, no dosage adjustments are necessary due to the broad therapeutic index of aciclovir.

Cream

No clinically significant interactions have been identified.

04.6 Pregnancy and breastfeeding -

Fertility

There are no data on fertility in women. Aciclovir tablets have not been shown to affect sperm count, morphology and motility in humans (see also section 5.3).

Pregnancy

Tablets, suspension and granules:

Since clinical data on administration in pregnancy are limited, during this period the drug should only be administered in cases of absolute necessity under direct medical supervision, when the potential benefits outweigh the possibility of unknown risks.

Cream:

The use of aciclovir should only be considered if the potential benefits outweigh the possibility of unknown risks, however the systemic exposure of aciclovir following topical application of aciclovir cream is very low.

A registry of post-marketing use of aciclovir in pregnancy provided data on pregnancy outcomes in women exposed to the various aciclovir formulations. These observations did not show an increase in the number of birth defects among subjects exposed to aciclovir in compared to the general population, and all the defects found at birth did not show any particularity or common characteristics, such as to suggest a single cause.

Systemic administration of Aciclovir in internationally accepted standard tests did not produce embryotoxic or teratogenic effects in rabbits, rats or mice.

In a non-standard rat test, fetal abnormalities were observed after subcutaneous doses of Aciclovir so high that they produced toxic effects on the mother. The clinical relevance of these findings is uncertain.

Feeding time

Tablets, suspension and granules:

Following oral administration of Aciclovir 200 mg, 5 times / day, the presence of Aciclovir in breast milk was observed at concentrations equal to 0.6-4.1 times the corresponding plasma levels. Such levels would potentially expose infants to Aciclovir doses up to 0.3 mg / kg / day. Therefore, the use of Aciclovir during breastfeeding should be avoided.

Cream:

Limited data indicate that the drug is found in breast milk following systemic administration. However, the dose received by an infant following the use of aciclovir cream in the mother should be insignificant.

04.7 Effects on ability to drive and use machines -

Tablets, suspension and granules:

The clinical condition of the patient and the adverse event profile of aciclovir should be taken into account with regard to the patient's ability to drive and use machines.

No studies have been performed to investigate the effects of aciclovir on the ability to drive and operate machinery. Further harmful effects on these activities cannot be predicted from the pharmacology of the active ingredient.

04.8 Undesirable effects -

Tablets, suspension and granules

The frequency categories associated with the adverse events listed below are estimates. For most events, adequate incidence assessment data are not available. In addition, the incidence of adverse events may vary by indication.

The following convention has been used for the classification of undesirable effects in terms of frequency: - very common ≥ 1/10, common ≥1 / 100 and

Disorders of the blood and lymphatic system

Very rare: anemia, leukopenia, thrombocytopenia

Disorders of the immune system

Rare: anaphylaxis

Psychiatric disorders and pathologies of the nervous system

Common: headache, dizziness

Very rare: agitation, confusional state, tremor, ataxia, dysarthria, hallucinations, psychotic symptoms, convulsions, somnolence, encephalopathy, coma

The above events are generally reversible and usually occur in patients with renal insufficiency or other predisposing factors (see section 4.4).

Respiratory, thoracic and mediastinal disorders

Rare: dyspnoea

Gastrointestinal disorders

Common: nausea, vomiting, diarrhea, abdominal pain

Hepatobiliary disorders

Rare: reversible increases in bilirubin and liver enzymes

Very rare: hepatitis, jaundice

Skin and subcutaneous tissue disorders

Common: pruritus, rash (including photosensitivity)

Uncommon: urticaria. Rapid and widespread hair loss

Rapid and widespread hair loss has been associated with a "wide range of conditions and drug use," so the relationship of this occurrence to acyclovir therapy is uncertain.

Rare: angioedema

Renal and urinary disorders

Rare: increases in blood levels of urea nitrogen and creatinine

Very rare: acute renal failure, renal pain

Kidney pain can be associated with kidney failure.

General disorders and administration site conditions

Common: fatigue, fever

Cream

The following convention has been used for the classification of undesirable effects in terms of frequency: very common> 1/10, common> 1/100 and 1 / 1,000 and 1 / 10,000 and

Data from clinical trials were used to assign frequency categories to adverse reactions observed during clinical trials performed with aciclovir 3% ophthalmic ointment. Due to the nature of the adverse events observed, it is not possible to uniquely determine which events are related to drug administration and which are related to the disease itself. Data from spontaneous reporting was used as a basis for determining the frequency of those events detected by post-marketing pharmacovigilance.

Skin and subcutaneous tissue disorders

Uncommon: transient burning or pain after application of aciclovir cream

moderate dryness or peeling of the skin

itch

Rare: erythema. Contact dermatitis after application. Where sensitivity tests were conducted, it was shown that the substances that gave phenomena of reactivity were the components of the base cream rather than acyclovir.

Disorders of the immune system

Very rare: immediate hypersensitivity reactions including angioedema and urticaria.

04.9 Overdose -

Tablets, suspension and granules:

Signs and symptoms

Aciclovir is only partially absorbed from the gut. Patients who have ingested an overdose of up to 20 g of aciclovir in a single dose generally have no toxic effects. Accidental and repeated overdoses of oral aciclovir over several days are reported. states associated with gastrointestinal effects (such as nausea and vomiting) and neurological effects (headache and confusion).

Overdose of intravenous aciclovir has resulted in increased serum creatinine, blood urea nitrogen and subsequent renal failure. Neurological effects including confusion, hallucinations, agitation, convulsions and coma have been reported in conjunction with overdose.

Treatment

Patients should be carefully observed for any signs of toxicity. Hemodialysis significantly increases the elimination of aciclovir from the blood and can therefore be considered an option in the management of drug overdose.

Cream: Even if the entire contents of a tube of cream containing 500 mg of acyclovir are ingested, no undesirable effects should be expected.

05.0 PHARMACOLOGICAL PROPERTIES -

05.1 "Pharmacodynamic properties -

Pharmacotherapeutic group: Antivirals for systemic use, J05AB1 (Tablets, suspension and granules)

Pharmacotherapeutic group: Topical chemotherapeutic agents - antivirals; D06BB03 (Cream)

Aciclovir is a synthetic purine nucleoside analog with inhibitory activity, in vitro and in vivo, against human herpetic viruses, including the Herpes Simplex virus (HSV) type 1 and 2 and the Varicella Zoster virus (VZV). In cultures cellular, Aciclovir showed the greatest antiviral activity against HSV-1, followed by HSV-2.

The inhibitory activity of Aciclovir against HSV-1 and HSV-2 is highly selective.

The thymidine kinase enzyme of normal, uninfected cells does not effectively use Acyclovir as a substrate; therefore the toxicity for the host cells is low; on the contrary, viral thymidine kinase converts Aciclovir into Aciclovir monophosphate, a nucleoside analogue, which is further converted into di-phosphate and tri-phosphate by cellular enzymes. Aciclovir tri-phosphate interferes with viral DNA polymerase and inhibits viral DNA replication; its incorporation into the viral DNA causes the interruption of the catenary elongation process of the latter.

Prolonged or repeated courses of Aciclovir in severely immunocompromised patients may be associated with the selection of viral strains with reduced sensitivity, which may not respond to continued treatment with Aciclovir.

Most of the isolated viral strains, with reduced sensitivity, showed a relative deficiency of viral thymidine kinase; however, strains with altered viral thymidine kinase or DNA polymerase have also been observed. In vitro exposure of isolated HSV strains to Aciclovir may also be associated with the appearance of less sensitive strains. The relationship between the sensitivity, determined in vitro, of isolated HSV strains and the clinical response to Aciclovir therapy , is not clarified.

05.2 "Pharmacokinetic properties -

Aciclovir is only partially absorbed from the intestine.

Peak steady state plasma concentrations (Cssmax) after doses of 200 mg every 4 hours is 3.1 mcMol (0.7 mcg / ml) and the trough concentration (Cssmin) is 1.8 mcMol (0.4 mcg / ml).

After doses of 400 mg and 800 mg every 4 hours the Cssmax is, respectively, 5.3 mcMol (1.2 mcg / ml) and 8 mcMol (1.8 mcg / ml) and the Cssmin is, respectively, 2.7 mcMol (0.6 mcg / ml) and 4 mcMol (0.9 mcg / ml).

From studies with aciclovir administered intravenously, the half-life of the drug is approximately 2.9 hours. Most of the drug is excreted unchanged via the kidney. The renal clearance of Aciclovir is considerably greater than that of creatinine, indicating that in addition to glomerular filtration contributes to the renal elimination of the drug tubular secretion. The only important metabolite is 9-carboxymethoxymethylguanine corresponding to approximately 10-15% of the urinary excreted dose.

In the elderly, total clearance decreases with increasing age along with creatinine clearance, however there are slight changes in the terminal plasma half-life.

In patients with chronic renal insufficiency, the mean half-life is 19.5 hours while during hemodialysis the mean half-life of Aciclovir is 5.7 hours and the levels are reduced by an average of about 60%.

The drug levels in the CSF are approximately 50% of the plasma levels. Plasma protein binding is relatively poor (9 to 33%) and drug interactions due to binding site displacement are not expected.

05.3 Preclinical safety data -

Mutagenicity

The results of a large number of in vitro and in vivo mutagenicity tests indicate that Aciclovir does not pose genetic risks for humans.

Carcinogenesis

In long-term studies in rats and mice, Acyclovir was not found to be carcinogenic.

Fertility

Reversible toxic effects on spermatogenesis have been reported in rats and dogs only at doses significantly higher than therapeutic ones. Two-generation studies in mice revealed no effects of aciclovir, administered orally, on fertility.

06.0 PHARMACEUTICAL INFORMATION -

06.1 Excipients -

Aciclin 200 mg Tablets

Lactose; Microcrystalline cellulose; Starch and sodium glycollate; Polyvinylpyrrolidone; Magnesium stearate.

Aciclin 400 mg Tablets

Microcrystalline cellulose; Starch and sodium glycollate; Polyvinylpyrrolidone; Magnesium stearate.

Aciclin 800 mg Tablets

Microcrystalline cellulose; Starch and sodium glycollate; Polyvinylpyrrolidone; Magnesium stearate.

Aciclin 400 mg / 5ml oral suspension

Non crystallizable sorbitol; Glycerol; Pulverized cellulose; Methyl p-hydroxybenzoate; Propyl p-hydroxybenzoate; Aroma of black cherry purified water.

Aciclin 800 mg Granules for oral suspension

Lactose, Carboxymethylcellulose, Aspartame, Strawberry Flavor, Sucrose.

Aciclin 5% Cream

Tefose 1500, Glycerin, Stearic acid, Liquid paraffin, Methylparaben, Purified water q.s. to 100 g.

06.2 Incompatibility "-

Incompatibilities with other medicines are unknown.

06.3 Period of validity "-

200 mg tablets: 5 years

400 mg tablets: 5 years

800 mg tablets: 5 years

400 mg / 5ml oral suspension: 3 years

800 mg granules: 3 years

5% cream: 3 years

06.4 Special precautions for storage -

800 mg tablets: store away from moisture.

5% cream: do not store above 25 ° C.

06.5 Nature of the immediate packaging and contents of the package -

Aciclin 200 mg Tablets: box of 25 tablets in blister

Aciclin 400 mg Tablets: box of 25 tablets in blister

Aciclin 800 mg Tablets: box of 35 tablets in blister

Aciclin 400 mg / 5ml oral suspension: 100ml glass bottle

Aciclin 800 mg granules for oral suspension: 35 Paper / aluminum / polythene sachets

Aciclin 5% - cream, 10 g tube

06.6 Instructions for use and handling -

Suspension: shake before use.

Sachets of granules: dissolve the contents of one sachet in half a glass of water and shake the suspension.

07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -

FIDIA Farmaceutici S.p.A. - Via Ponte della Fabbrica, 3 / A - 35031 ABANO TERME (PD)

08.0 MARKETING AUTHORIZATION NUMBER -

Aciclin 200 mg - tablets: AIC 028614042

Aciclin 400 mg - tablets: AIC 028614055

Aciclin 800 mg - tablets: AIC 028614081

Aciclin 400 mg / 5ml oral suspension: AIC 028614129

Aciclin 800 mg granules for oral suspension: AIC 028614131

Aciclin 5% - cream 10 g: AIC 028614156

09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -

Aciclin 200 mg - tablets: 28.10.94 / 15.11.09

Aciclin 400 mg - tablets: 28.10.94715.11.09

Aciclin 800 mg - tablets: 22.12.99 / 15.11.09

Aciclin 400 mg / 5ml oral suspension: 07.10.03 / 15.11.09

Aciclin 800 mg granules for oral suspension: 07.10.03 / 15.11.09

Aciclin 5% - cream 10 g: 30.07.04 / 15.11.09

10.0 DATE OF REVISION OF THE TEXT -

13.08.2011

11.0 FOR RADIO DRUGS, COMPLETE DATA ON THE INTERNAL RADIATION DOSIMETRY -

12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON EXEMPORARY PREPARATION AND QUALITY CONTROL -

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