Aciclovir dorom - 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

ACICLOVIR DOROM 400 mg tablets
ACICLOVIR DOROM 800 mg tablets
ACICLOVIR DOROM 400 mg / 5 ml oral suspension

Aciclovir dorom package inserts are available for pack sizes:
  • ACICLOVIR DOROM 400 mg tablets, ACICLOVIR DOROM 800 mg tablets, ACICLOVIR DOROM 400 mg / 5 ml oral suspension
  • ACICLOVIR DOROM 5% cream

Why is Aciclovir dorom used? What is it for?

PHARMACOTHERAPEUTIC CATEGORY

Antiviral chemotherapy.

THERAPEUTIC INDICATIONS

ACICLOVIR DOROM is indicated:

  • for the treatment of herpes simplex virus (HSV) infections of the skin and mucous membranes, including primary and relapsing herpes genitalis (excluding neonatal HSV and severe HSV infections in immunocompromised children);
  • for the suppression of Herpes simplex relapses, in patients with normal immune function;
  • for the prophylaxis of Herpes simplex infections in patients with impaired immune function;
  • for the treatment of chickenpox and herpes zoster.

Contraindications When Aciclovir dorom should not be used

Hypersensitivity to the active substance, to valaciclovir or to any of the excipients.

Precautions for use What you need to know before taking Aciclovir dorom

State of hydration:

ensure that adequate hydration is maintained in patients taking high doses of oral or intravenous aciclovir. The risk of renal impairment is increased by the use of other nephrotoxic drugs.

Use in patients with renal insufficiency or elderly patients:

aciclovir is eliminated by renal clearance, therefore the dose should be reduced in patients with renal insufficiency (see section "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 section "Undesirable effects").

Prolonged or repeated courses of aciclovir treatment in severely immunocompromised individuals may result in the selection of resistant viral strains with reduced sensitivity that may not respond to continued aciclovir treatment.

Interactions Which drugs or foods can modify the effect of Aciclovir dorom

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

Aciclovir is eliminated mainly unchanged in the urine by active renal tubular secretion. Any concomitantly administered drug that competes with this mechanism may increase the plasma concentrations of aciclovir. Probenecid and cimetidine increase the AUC of aciclovir through this mechanism and decrease the renal clearance of aciclovir. Similarly, increases in the plasma AUC of aciclovir and the inactive metabolite of mycophenolate mofetil, an immunosuppressant used in transplant patients, have been shown when drugs are used. administered concomitantly. However, no dose adjustment is necessary due to the broad therapeutic index of aciclovir.

An experimental study in five male subjects indicates that concomitant therapy with aciclovir increases the AUC of administered theophylline by approximately 50%. It is recommended that plasma concentrations of theophylline be measured during concomitant therapy with aciclovir.

Warnings It is important to know that:

Pregnancy and breastfeeding

Ask your doctor or pharmacist for advice before taking any medicine

Pregnancy

The use of aciclovir should only be considered if the potential benefits outweigh the possibility of unknown risks.

A registry on the use of aciclovir in pregnancy provided data on pregnancy outcomes in women exposed to various formulations of aciclovir after marketing. These observations did not show an increase in the number of congenital anomalies in subjects exposed to aciclovir compared to the general population. , and the congenital anomalies observed did not reveal characteristics of uniqueness or concordance such as to suggest a possible common cause for their onset.

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

In an experimental test not included in the standard tests conducted on rats, fetal abnormalities were observed but only following subcutaneous doses so high as to induce toxic effects on the mother.

The clinical relevance of these data is uncertain.

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.

Feeding time

Following oral administration of aciclovir 200 mg five times daily, aciclovir was detected in breast milk at concentrations 0.6-4.1 times the corresponding plasma levels.

These levels potentially expose infants to aciclovir doses up to 0.3 mg / kg / day. Therefore, caution is advised when aciclovir is to be administered to a nursing woman.

Fertility

No data on female fertility are available. Aciclovir has not been shown to affect sperm count, morphology and motility in humans.

Effects on ability to drive and use machines

The clinical status of the patient and the adverse event profile of aciclovir should be taken into account when considering patients' ability to drive or operate machinery.

No studies have been conducted to evaluate the effect of aciclovir on the ability to drive or use machines. Furthermore, a negative effect on these activities cannot be predicted from the pharmacology of the active substance.

ACICLOVIR DOROM tablets contain lactose: if you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

ACICLOVIR DOROM oral suspension contains sorbitol: if you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine. It may have a mild laxative effect. The caloric value of sorbitol is 2.6 kcal / g. ACICLOVIR DOROM oral suspension contains methyl parahydroxybenzoate and propyl parahydroxybenzoate: they can cause allergic reactions, even delayed.

Dosage and method of use How to use Aciclovir dorom: Dosage

Adults

Treatment of Herpes simplex infections: 200 mg (equivalent to 2.5 ml of oral suspension) 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 (e.g. after a bone marrow transplant) or in patients with impaired absorption from the gut, the dosage can be doubled to 400 mg tablets or 5 ml oral suspension or, alternatively, it can be the advisability of intravenous administration of aciclovir has been evaluated. Therapy should be started as soon as possible after the "onset of" infection and, in the case of recurrent infections, this should preferably occur at the first symptoms or when the first lesions appear.

Suppressive therapy of relapse of Herpes simplex infections in patients with normal immune function: 200 mg (equivalent to 2.5 ml of oral suspension) 4 times a day at 6 hour intervals. Many patients can be successfully treated by administering 400 mg tablets or 5 ml oral 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. In some patients, recurrence of the infection may occur with a total daily dose of 800 mg of ACICLOVIR DOROM. Therapy should be interrupted periodically at intervals of 6 or 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: 200 mg (equivalent to 2.5 ml of oral suspension) 4 times a day at 6 hour intervals. In patients with severely impaired immune function (e.g. after a bone marrow transplant) or in patients with impaired absorption from the gut the dosage can be doubled to 400 mg in tablets or 5 ml oral suspension or, alternatively, it can be evaluated. the advisability of intravenous administration of aciclovir. The duration of prophylaxis should be considered in relation to that of the risk period.

Treatment of herpes zoster and chickenpox:

Recruitment schedule throughout the day Hours of the day 7.00 am breakfast 11.00 late in the morning 15.00 early afternoon 19.00 late afternoon 11.00 pm in the evening

800 mg in tablets or 10 ml of oral 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 severely impaired immune function (eg after a bone marrow transplant) or in patients with impaired intestinal absorption, intravenous administration of aciclovir may be considered. "infection, in fact the treatment gets better results if started when the first lesions appear.

Dosage in children

For the treatment of Herpes simplex infections and for their prophylaxis in those with impaired immune function, the dosage in children over 2 years of age is similar to that in adults. Under 2 years the dosage is reduced by half. Serious HSV infections in the immunocompromised, for which ACICLOVIR DOROM is not indicated are exceptions (see section "Therapeutic indications").

For the treatment of chickenpox, in children over 6 years of age the dosage is 800 mg in tablets or 10 ml of oral suspension 4 times a day; in those aged between 2 and 6 years the dosage is 400 mg in tablets or 5 ml of oral suspension 4 times a day; in those younger than 2 years the recommended dosage is 200 mg (2.5 ml of oral 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, administration of acyclovir by route should be considered. intravenous.

Dosage in elderly patients

Adequate hydration should be maintained in patients taking high doses of oral ACICLOVIR DOROM. The possibility of renal impairment should be taken into account in the elderly and the dosage should be adjusted accordingly (see "Dosage in patients with renal insufficiency" below).

Dosage in patients with renal insufficiency

Caution is advised when administering aciclovir to patients with impaired renal function. Adequate hydration must be maintained.

In the treatment and prophylaxis of Herpes simplex infections, in patients with impaired renal function, the recommended oral posology should not cause accumulation of aciclovir above the levels that have been shown to be tolerated following intravenous administration of the drug. In the management of Herpes simplex infections in patients with severe renal impairment (creatinine clearance less than 10 ml / min), it is recommended to adjust the aciclovir dose to 200 mg administered twice daily at approximately 12 hour intervals.

In the treatment of varicella and herpes zoster infections it is recommended that the dosage be changed to 800 mg aciclovir in tablets or 10 ml suspension, administered twice daily at approximately 12 hour intervals, in patients with severe renal impairment (clearance less than 10 ml / min) and 800 mg of aciclovir in tablets 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).

Overdose What to do if you have taken an overdose of Aciclovir dorom

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

Symptoms and signs

Aciclovir is only partially absorbed from the gastrointestinal tract. Some patients have ingested overdoses of up to 20 g of aciclovir in a single administration without exhibiting toxic effects.

Accidental 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). Overdoses of intravenous aciclovir have resulted in increases in serum creatinine levels, blood urea nitrogen resulting in renal failure. Neurological effects including confusion, hallucinations, agitation, convulsions and coma, associated with overdose have been described.

Treatment

Patients should be monitored closely for signs of toxicity. Hemodialysis significantly increases the elimination of aciclovir from the blood and therefore can be considered a therapeutic option in the event of symptomatic overdose.

If you have any further questions on the use of ACICLOVIR DOROM, ask your doctor or pharmacist.

Side Effects What are the side effects of Aciclovir dorom

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

The frequency categories associated with the underlying adverse events were estimated. For most events, adequate data were not available to assess the incidence. In addition, adverse events may vary according to their incidence depending on the indication.

The following convention has been used for the classification of undesirable effects in terms of frequency: very common (≥1 / 10), common (≥1 / 100 to <1/10), uncommon (≥1 / 1,000 to <1 / 100), rare (≥1 / 10,000, <1 / 1,000), very rare (<1 / 10,000), not known (cannot be estimated from the available data).

Disorders of the blood and lymphatic system

Very rare: anemia, leukopenia, thrombocytopenia

Disorders of the immune system

Rare: anaphylaxis

Psychiatric and nervous system disorders *

Common: headache, dizziness

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

* The above events are generally reversible and are normally reported in patients with renal insufficiency or other predisposing factors (see section "Precautions for use").

Respiratory, thoracic and mediastinal disorders

Rare: dyspnoea

Gastrointestinal disorders

Common: nausea, vomiting, diarrhea, abdominal pain

Hepatobiliary disorders

Rare: Reversible increases in bilirubin and related liver enzymes

Very rare: hepatitis, jaundice

Skin and subcutaneous tissue disorders

Common: pruritus, rash (incl. Photosensitivity)

Uncommon: hives, rapid and widespread hair loss

Rapid and widespread hair loss has been associated with a "wide variety of pathological and medicinal processes; the relationship of the event with acyclovir therapy is uncertain."

Rare: angioedema

Renal and urinary disorders

Rare: increases in serum BUN 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.Following the instructions contained in the package leaflet reduces the risk of side effects.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. Side effects can also be reported directly via the national reporting system at www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicine.

Expiry and Retention

ACICLOVIR DOROM 8% oral suspension: Store below 25 ° C.

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

Warning: do not use the medicine after the expiry date indicated on the package.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use.This will help protect the environment.

KEEP THE MEDICINAL PRODUCT OUT OF THE REACH AND SIGHT OF CHILDREN.

Deadline "> Other information

COMPOSITION

ACICLOVIR DOROM 400 mg tablets

Each 400 mg tablet contains:

  • active ingredient: aciclovir 400 mg;
  • excipients: lactose; cornstarch; crospovidone; magnesium stearate.

ACICLOVIR DOROM 800 mg tablets

Each 800 mg tablet contains:

  • active ingredient: aciclovir 800 mg;
  • excipients: lactose; cornstarch; crospovidone; magnesium stearate.

ACICLOVIR DOROM 400 mg / 5 ml oral suspension

100 ml of oral suspension contain:

  • active ingredient: aciclovir g 8;
  • excipients: non crystallizable liquid sorbitol; glycerol; dispersible cellulose; methyl para-hydroxybenzoate; propyl parahydroxybenzoate; orange flavor; purified water.

PHARMACEUTICAL FORM AND CONTENT

Tablets for oral use: 35 tablets 800 mg; 25 tablets 400 mg

Oral suspension: Bottle of 100 ml

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 Aciclovir dorom can be found 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 -

ACICLOVIR DOROM

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -

ACICLOVIR DOROM 400 mg tablets

One tablet contains: 400 mg aciclovir

ACICLOVIR DOROM 800 mg tablets

One tablet contains: aciclovir 800 mg

Excipients with known effects: lactose.

ACICLOVIR DOROM 400 mg / 5 ml oral suspension

100 ml of oral suspension contain: aciclovir 8 g

Excipients with known effects: sorbitol, methyl para-hydroxybenzoate and propyl para-hydroxybenzoate.

For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM -

Tablets.

Oral suspension.

04.0 CLINICAL INFORMATION -

04.1 Therapeutic indications -

ACICLOVIR DOROM is indicated:

• for the treatment of Herpes simplex virus (HSV) infections of the skin and mucous membranes, including primary and relapsing herpes genitalis (excluding neonatal HSV and severe HSV infections in immunocompromised children);

• 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.

04.2 Posology and method of administration -

Dosage

Adults

Treatment of Herpes simplex infections: 200 mg (equivalent to 2.5 ml of oral suspension) 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 severely immunocompromised patients (eg after bone marrow transplantation) or in patients with impaired absorption from the gut, the dosage can be doubled to 400 mg in tablets or 5 ml oral suspension or, alternatively, the advisability of an intravenous administration of aciclovir. Therapy should be started as early as possible from the first signs of an infection and, in the case of recurrent infections, this should preferably occur during the prodromal phase or when the first lesions appear.

Suppressive therapy of relapses of Herpes simplex infections in immunocompetent patients: 200 mg (equivalent to 2.5 ml of oral suspension) 4 times a day at 6 hour intervals. Many patients can be successfully treated by administering 400 mg tablets or 5 ml oral 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. In some patients, recurrence of the infection may occur with a total daily dose of 800 mg of ACICLOVIR DOROM. Therapy should be interrupted periodically at intervals of 6 or 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 (equivalent to 2.5 ml of oral suspension) 4 times a day at 6 hour intervals. In severely immunocompromised patients (eg after bone marrow transplantation) or in patients with impaired intestinal absorption the dosage can be doubled to 400 mg in tablets or 5 ml oral suspension or, alternatively, the advisability of a intravenous administration of aciclovir. The duration of prophylaxis must be considered in relation to that of the risk period.

Treatment of herpes zoster and chickenpox: 800 mg in tablets or 10 ml of oral 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 a bone marrow transplant) or in patients with impaired intestinal absorption, intravenous administration of aciclovir may be considered. Therapy should be initiated soon after the onset of infection. , in fact, the treatment obtains better results if established when the first lesions appear.

Pediatric population

For the treatment of Herpes simplex infections and for their prophylaxis in immunocompromised children, the dosage is similar to that of adults in children over 2 years of age. Under 2 years the dosage is reduced by half. Serious HSV infections in the immunocompromised, for which ACICLOVIR DOROM is not indicated is an exception (see section 4.1).

For the treatment of chickenpox, in children over 6 years of age the dosage is 800 mg in tablets or 10 ml of oral suspension 4 times a day; in those aged between 2 and 6 years the dosage is 400 mg in tablets or 5 ml of oral suspension 4 times a day; in those younger than 2 years the recommended dosage is 200 mg (2.5 ml of oral 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 immunocompetent children. Intravenous administration of aciclovir should be considered for the treatment of herpes zoster in immunocompromised children.

Dosage in elderly patients

Adequate hydration should be maintained in patients taking high doses of oral aciclovir. The possibility of renal impairment should be taken into account in the elderly and the dosage should be adjusted accordingly (see "Dosage in patients with renal insufficiency" below).

Dosage in patients with renal insufficiency

Caution is advised when administering aciclovir to patients with impaired renal function. Adequate hydration must be maintained.

In the treatment and prophylaxis of Herpes simplex infections, in patients with reduced renal function the recommended oral dosage should not cause an accumulation of aciclovir above the levels deemed acceptable for intravenous administration of the drug. In the management of Herpes simplex infections 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 varicella and herpes zoster infections it is recommended that the dosage be changed to 800 mg in tablets or 10 ml suspension administered twice daily at approximately 12 hour intervals in patients with severe renal insufficiency (creatinine clearance less than 10 ml / min) and 800 mg in tablets or 10 ml suspension 3 times a day, administered at intervals of approximately 8 hours, in patients with moderate renal insufficiency (creatinine clearance between 10 and 25 ml / min).

04.3 Contraindications -

Hypersensitivity to the active substance, to valaciclovir or to any of the excipients listed in section 6.1.

04.4 Special warnings and appropriate precautions for use -

Adequate hydration should be maintained in patients administered intravenous aciclovir or high doses of oral aciclovir.

The risk of renal impairment is increased by the use of other nephrotoxic drugs.

Use in patients with renal insufficiency or in 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 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 section 4.8).

Prolonged or repeated treatment courses of aciclovir in severely immunocompromised individuals may result in the selection of resistant viral strains with reduced sensitivity that may not respond to continued aciclovir treatment (see section 5.1).

ACICLOVIR DOROM tablets contain lactose: patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.

ACICLOVIR DOROM oral suspension contains sorbitol: patients with rare hereditary problems of fructose intolerance should not take this medicine. It may have a mild laxative effect. The caloric value of sorbitol is 2.6 kcal / g.

ACICLOVIR DOROM oral suspension contains methyl para-hydroxybenzoate and propyl para-hydroxybenzoate. It can cause allergic reactions (even delayed).

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

Aciclovir is eliminated mainly unchanged in the urine by active renal tubular secretion. Any concomitantly administered drug that competes with this mechanism may increase the plasma concentrations of aciclovir. Probenecid and cimetidine increase the AUC of aciclovir through this mechanism and decrease the renal clearance of aciclovir. Similarly, increases in the plasma AUC of aciclovir and the inactive metabolite of mycophenolate mofetil, an immunosuppressant used in transplant patients, have been shown when drugs are used. administered concomitantly. However, no dose adjustment is necessary due to the broad therapeutic index of aciclovir.

An experimental study in five male subjects indicates that concomitant therapy with aciclovir increases the AUC of administered theophylline by approximately 50%. It is recommended that plasma concentrations of theophylline be measured during concomitant therapy with aciclovir.

04.6 Pregnancy and breastfeeding -

Fertility

See clinical studies section 5.2 and section 5.3.

No data on female fertility are available. Aciclovir has not been shown to affect sperm count, morphology and motility in humans.

Pregnancy

The use of aciclovir should only be considered if the potential benefits outweigh the possibility of unknown risks.

A registry on the use of aciclovir in pregnancy provided data on pregnancy outcomes in women exposed to various formulations of aciclovir after marketing. These observations did not show an increase in the number of congenital anomalies in subjects exposed to aciclovir compared to the general population. , and the congenital anomalies observed did not reveal characteristics of uniqueness or concordance such as to suggest a possible common cause for their onset.

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

In an experimental test not included in the standard tests conducted on rats, fetal abnormalities were observed but only following subcutaneous doses so high as to induce toxic effects on the mother. The clinical relevance of these data is uncertain.

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.

Feeding time

Following oral administration of aciclovir 200 mg five times daily, aciclovir was detected in breast milk at concentrations 0.6-4.1 times the corresponding plasma levels. These levels potentially expose infants to aciclovir doses up to 0.3 mg / kg / day. Therefore, caution is advised when aciclovir is to be administered to a nursing woman.

04.7 Effects on ability to drive and use machines -

The clinical status of the patient and the adverse event profile of aciclovir should be taken into account when considering patients' ability to drive or operate machinery.

No studies have been conducted to evaluate the effect of aciclovir on the ability to drive or use machines. Furthermore, harmful effects on these activities cannot be predicted from the pharmacology of the active substance.

04.8 Undesirable effects -

The frequency categories associated with the underlying adverse events were estimated. For most events, adequate data were not available to assess the incidence. In addition, adverse events may vary according to their incidence depending on the indication.

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

Disorders of the blood and lymphatic system

Very rare: anemia, leukopenia, thrombocytopenia.

Disorders of the immune system

Rare: anaphylaxis.

Psychiatric and nervous system disorders *

Common: headache, dizziness

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

* The above events are generally reversible and are normally reported 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 related liver enzymes

Very rare: hepatitis, jaundice.

Skin and subcutaneous tissue disorders

Common: pruritus, rash (including photosensitivity)

Uncommon: hives, rapid and widespread hair loss

Rapid and widespread hair loss has been associated with a "wide variety of pathological and medicinal processes; the relationship of the event with acyclovir therapy is uncertain."

Rare: angioedema

Renal and urinary disorders

Rare: increases in serum BUN 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.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address www.agenziafarmaco.gov.it/it/responsabili.

04.9 Overdose -

Symptoms and signs

Aciclovir is only partially absorbed from the gastrointestinal tract. Some patients have ingested overdoses of up to 20 g of aciclovir in a single administration without exhibiting toxic effects.Accidental 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).

Overdoses of intravenous aciclovir have resulted in increases in serum creatinine levels, blood urea nitrogen resulting in renal failure. Neurological effects including confusion, hallucinations, agitation, convulsions and coma, associated with overdose have been described.

Treatment

Patients should be monitored closely for signs of toxicity. Hemodialysis significantly increases the elimination of aciclovir from the blood and therefore can be considered a therapeutic option in the event of symptomatic overdose.

05.0 PHARMACOLOGICAL PROPERTIES -

05.1 "Pharmacodynamic properties -

Pharmacotherapeutic group: Direct acting antivirals for systemic use - nucleosides and nucleotides excluding reverse transcriptase inhibitors, ATC code: J05AB01.

Mechanism of action

Aciclovir is a synthetic purine nucleoside analog with inhibitory activity, in vitro and in vivo, against human herpes viruses, including Herpes simplex virus (HSV) types 1 and 2, Varicella zoster virus (VZV), Epstein Barr virus (EBV) and cytomegalovirus (CMV). In cell cultures, aciclovir showed the greatest antiviral activity against HSV-1, followed (in order of decreasing potency) by HSV-2, VZV, EBV and CMV. The inhibitory activity of aciclovir against HSV -1, HSV-2, VZV, EBV and CMV is highly selective. The thymidine kinase (TK) enzyme of normal, uninfected cells does not effectively use acyclovir as a substrate; therefore toxicity to mammalian host cells on the contrary, the viral thymidine kinase encoded by HSV, VZV and EBV converts aciclovir into aciclovir monophosphate, a nucleoside analogue, which is further converted into diphosphate and triphosphate by cellular enzymes. Acyclovir triphosphate interferes with viral DNA-polymerase and inhibits viral DNA replication; its incorporation into viral DNA causes the interruption of the DNA chain elongation process.

Pharmacodynamic 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 prolonged aciclovir treatment.

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. Even the exhibition, in vitro, to aciclovir, of isolated HSV strains, may be associated with the appearance of less sensitive strains. The relationship between sensitivity, determined in vitro, of the isolated HSV strains and the clinical response to aciclovir therapy is unclear.

All patients should be advised to try to avoid any possible transmission of the virus, particularly when active lesions are present.

05.2 "Pharmacokinetic properties -

Absorption

Aciclovir is only partially absorbed from the intestine.

Peak steady state plasma concentrations (Cssmax) after doses of 200 mg every 4 hours are approximately 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) in adults.

In adults, the mean Cssmax after a one-hour infusion of 2.5 mg / kg, 5 mg / kg and 10 mg / kg is 22.7 mcMol (5.1 mcg / ml), 43.6 mcMol ( 9.8 mcg / ml) and 92 mcMol (20.7 mcg / ml). The corresponding trough levels of Cssmin after 7 hours are, respectively, 2.2 mcMol (0.5 mcg / ml), 3.1 mcMol ( 0.7 mcg / mL) and 10.2 mcMol (2.3 mcg / mL).

In children over one year of age, similar mean levels of Cssmax and Cssmin were observed when a dose of 5 mg / kg was administered instead of the 250 mg / m² dose and a dose of 500 mg / m² dose of 10 mg / kg. In infants up to 3 months of age, treatment with a dose of 10 mg / kg administered as a one-hour infusion at 8-hour intervals, the Cssmax was 61.2 mcMol (13.8 mcg / ml) and the Cssmin was 10.1 mcMol (2.3 mcg / ml). A separate group of infants treated with 15 mg / kg every 8 hours showed approximately dose proportional increases, with a Cmax 83.5 micromolar (18.8 mcg / ml) and a Cmin 14.1 micromolar (3.2 mcg / ml).

Distribution

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.

Elimination

In adults aciclovir administered intravenously, the terminal 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, tubular secretion contributes to the renal elimination of the drug. The only important metabolite is 9-carboxymethoxymethylguanine corresponding to about 10-15% of the administered dose recovered in the urine. When aciclovir is administered one hour after administration of 1 g probenecid, the terminal half-life and area under the plasma concentration versus time curve extends by 18% and 40%, respectively.

In infants up to 3 months of age treated with a dose of 10 mg / kg administered as a one-hour infusion at 8-hour intervals, the terminal plasma half-life is 3.8 hours.

Special populations

In patients with chronic renal failure, the mean half-life was found to be 19.5 hours. During hemodialysis, the mean half-life of aciclovir was 5.7 hours. Plasma levels of aciclovir are reduced by approximately 60% during dialysis. In the elderly, total clearance decreases with increasing age along with a decrease in creatinine clearance although there is a slight modification of the terminal plasma half-life. Studies have shown that there are no obvious changes in the pharmacokinetics of aciclovir or zidovudine when both are administered concurrently in HIV-infected patients.

Clinical Studies

There is no information on the effects of aciclovir oral formulations or solution for infusion on female fertility. In a study of 20 male patients with normal sperm counts, oral administration of aciclovir at doses up to 1 g per day for up to six months was shown to have no clinically significant effect on number, motility or the morphology of spermatozoa.

05.3 Preclinical safety data -

Mutagenesis

The results of a large number of mutagenicity tests in vitro and in vivo indicate that acyclovir poses no genetic risk for humans.

Carcinogenesis

In long-term rat and mouse studies, acyclovir was not carcinogenic.

Fertility

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

Teratogenesis

Systemic administration of aciclovir using internationally accepted standard tests did not produce embryotoxic or teratogenic effects in rabbits, mice or rats. In an experimental test not included in the standard tests, conducted on rats, fetal abnormalities were observed, but only after subcutaneous doses of aciclovir so high as to produce toxic effects on the mother. The clinical relevance of these findings is uncertain.

06.0 PHARMACEUTICAL INFORMATION -

06.1 Excipients -

ACICLOVIR DOROM 400 mg tablets:

lactose; cornstarch; crospovidone; magnesium stearate.

ACICLOVIR DOROM 800 mg tablets:

lactose; cornstarch; crospovidone; magnesium stearate.

ACICLOVIR DOROM 400 mg / 5 ml oral suspension:

non-crystallizable liquid sorbitol; glycerol; dispersible cellulose; methyl parahydroxybenzoate; propyl parahydroxybenzoate; orange flavor; purified water.

06.2 Incompatibility "-

Not relevant.

06.3 Period of validity "-

ACICLOVIR DOROM 400 mg tablets - ACICLOVIR DOROM 800 mg tablets:

3 years.

ACICLOVIR DOROM 400 mg / 5 ml oral suspension:

2 years.

06.4 Special precautions for storage -

ACICLOVIR DOROM 400 mg tablets - ACICLOVIR DOROM 800 mg tablets:

There are no special precautions for storage.

ACICLOVIR DOROM 400 mg / 5 ml oral suspension:

Store below 25 ° C.

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

ACICLOVIR DOROM 400 mg tablets: 25 tablets in AL / PVDC / PVC blister packs

ACICLOVIR DOROM 800 mg tablets: 35 tablets in AL / PVDC / PVC blisters

ACICLOVIR DOROM 400 mg / 5 ml oral suspension: glass bottle of 100 ml with measuring cup.

Not all pack sizes may be marketed.

06.6 Instructions for use and handling -

Unused medicine and wastes derived from this medicine must be disposed of in accordance with local regulations

Shake the oral suspension before use.

07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -

Teva Italia S.r.l. - Piazzale Luigi Cadorna, 4 - 20123 Milan

08.0 MARKETING AUTHORIZATION NUMBER -

ACICLOVIR DOROM 400 mg tablets, 25 tablets A.I.C. n 028467037

ACICLOVIR DOROM 800 mg tablets, 35 tablets A.I.C. n 028467064

ACICLOVIR DOROM 400 mg / 5 ml oral suspension, fl. 100 ml A.I.C. n 028467049

09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -

ACICLOVIR DOROM 400 mg tablets

Date of first authorization: March 1993

Date of most recent renewal: April 2008

ACICLOVIR DOROM 800 mg tablets

Date of first authorization: March 1993

Date of most recent renewal: April 2008

ACICLOVIR DOROM 400 mg / 5 ml oral suspension

Date of first authorization: March 1993

Date of most recent renewal: April 2008

10.0 DATE OF REVISION OF THE TEXT -

February 2016

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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