Aciclovir Almus

ACICLOVIR ALMUS 800 mg tablets
ACICLOVIR ALMUS 400 mg/5 ml oral suspension
Equivalent medicinal product
PHARMACOTHERAPEUTIC CATEGORY
Antiviral for systemic use
THERAPEUTIC INDICATIONS
ACICLOVIR ALMUS is indicated:

• for the treatment of Herpes simplex infections of the skin and mucous membranes, including primary and recurrent genital herpes (excluding neonatal Herpes simplex infections and severe Herpes simplex infections in immunocompromised children).
• for the suppression of recurrent Herpes simplex infections in patients with normal immune function.
• for the prophylaxis of Herpes simplex infections in patients with impaired immune function.
• for the treatment of varicella and Herpes zoster.

CONTRAINDICATIONS
Aciclovir tablets and oral suspension are contraindicated in patients with known hypersensitivity to aciclovir, valaciclovir, or to any of the excipients.
Generally contraindicated during pregnancy and breastfeeding (see section “Special Warnings”).

PRECAUTIONS FOR USE
Hydration status: Adequate hydration must be maintained in patients receiving aciclovir intravenously or high oral doses of aciclovir.
The risk of renal damage is increased by the use of other nephrotoxic medicinal products.

Use in elderly patients and patients with renal impairment
Aciclovir is eliminated via renal clearance; therefore, dosage reduction is required in patients with renal impairment (see section "Dosage and method of administration").
Elderly patients are likely to have reduced renal function, and thus dose adjustment should be considered in this patient group. Both elderly patients and those with renal impairment are at increased risk of developing neurological adverse effects and should be closely monitored for their occurrence. In reported cases, these reactions were generally reversible upon discontinuation of treatment (see section “Undesirable effects”).

Prolonged and repeated courses of aciclovir treatment in severely immunocompromised individuals may lead to the selection of viral strains with reduced sensitivity, which might not respond to continued aciclovir therapy.

Children, Elderly, Patients with Specific Clinical Conditions
See "Dosage and method of administration".

INTERACTIONS
Inform your doctor or pharmacist if you have recently taken any other medicines, including those without a prescription.

Aciclovir is mainly excreted unchanged in urine through active tubular secretion. Any medicinal product administered concomitantly that competes with this mechanism may increase plasma concentrations of aciclovir. Probenecid and cimetidine, by this mechanism, increase the area under the plasma concentration-time curve of aciclovir and thus reduce its renal clearance. Similarly, concomitant administration of aciclovir and mycophenolate mofetil, an immunosuppressive agent used in transplant patients, increases the area under the plasma concentration-time curve of both aciclovir and the inactive metabolite of mycophenolate mofetil. Nevertheless, no dosage adjustment is required due to the wide therapeutic index of aciclovir.

An experimental study in five male subjects indicates that concomitant therapy with aciclovir increases the AUC of total theophylline by approximately 50%. Plasma concentration monitoring is recommended during concomitant therapy with aciclovir.

Other medicinal products affecting renal function may alter certain blood parameters of aciclovir.

SPECIAL WARNINGS
Pregnancy
Consult your doctor or pharmacist before taking any medicine.
Aciclovir Almus should be considered only when potential benefits outweigh the possibility of unknown risks. A registry on the use of aciclovir during pregnancy has provided data on pregnancy outcomes in women exposed to various aciclovir formulations after marketing authorization. These observations have not shown an increased number of birth defects among subjects exposed to aciclovir compared to the general population, and all observed birth defects did not show any particular pattern or common characteristics suggesting a single cause.

Breastfeeding
Following oral administration of 200 mg aciclovir five times daily, aciclovir has been detected in breast milk at concentrations of 0.6–4.1 times the corresponding plasma levels. These levels could potentially expose infants to aciclovir doses up to 0.3 mg/kg/day. Therefore, caution is advised when using aciclovir during breastfeeding.

Effects on ability to drive and use machines
No negative effects of aciclovir on the ability to drive or use machines are known.

Important information on certain excipients
ACICLOVIR ALMUS in the form of oral suspension contains:
Glycerol: glycerol may be harmful at high doses and can cause headache, stomach disturbances, and diarrhea.
ACICLOVIR ALMUS in the form of oral suspension contains 31.5 g of sorbitol. When taken according to the recommended dosage, each 5 ml dose provides up to 1.575 g of sorbitol. The product is unsuitable in cases of fructose intolerance and may cause gastrointestinal disturbances and diarrhea.

DOSAGE, METHOD AND TIME OF ADMINISTRATION
Shake the suspension before use.
The Aciclovir oral suspension pack includes a dosing cup with markings corresponding to 5 ml and 10 ml volumes.

Adults
Treatment of Herpes simplex infections
200 mg five times daily at approximately 4-hour intervals, omitting the nighttime dose. Treatment should continue for 5 days but may need to be prolonged in cases of severe primary infections.
In patients with severely impaired immune function (e.g., after bone marrow transplantation) or in patients with reduced intestinal absorption, the dosage may be doubled to 400 mg tablets or 5 ml of suspension, or alternatively, intravenous administration may be considered.
Treatment should be initiated as early as possible and, in recurrent infections, preferably at the first symptoms or appearance of initial lesions.

Suppressive therapy for recurrent Herpes simplex infections in patients with normal immune function
200 mg four times daily at 6-hour intervals.
Many patients can be successfully treated with 400 mg tablets or 5 ml of suspension twice daily at 12-hour intervals.
Effective regimens may also include 200 mg three times daily at 8-hour intervals or twice daily at 12-hour intervals.
Recurrences may occur in some patients even with a total daily dose of 800 mg aciclovir.
Therapy should be periodically interrupted at intervals of 6 or 12 months to assess any changes in the natural course of the disease.

Prophylaxis of Herpes simplex infections in patients with impaired immune function
200 mg four times daily at 6-hour intervals. In patients with severely impaired immune function (e.g., after bone marrow transplantation) or with reduced intestinal absorption, the dosage may be doubled to 400 mg tablets or 5 ml of suspension, or alternatively, intravenous administration may be considered.
The duration of prophylaxis should be determined according to the length of the risk period.

Treatment of Herpes zoster and varicella
Tablet dosing schedule throughout the day

800 mg as tablets or 10 ml of suspension 5 times a day at intervals of approximately 4 hours,
omitting the nighttime dose. Treatment should be continued for 7 days.
In patients with severely impaired immune function (e.g. after bone marrow transplantation) or in patients with reduced intestinal absorption, intravenous administration of the drug may be considered.
Treatment should be started immediately after the onset of infection, as therapy achieves better results when initiated at the first appearance of lesions.

Children
For the treatment of Herpes simplex infections and for prophylaxis in immunocompromised children over 2 years of age, the dosage is similar to that of adults. For children under 2 years of age, the dosage should be halved.
Severe HSV infections in immunocompromised patients are an exception, for which Aciclovir Almus is not indicated (see section "Therapeutic indications").
For the treatment of varicella, in children over 6 years of age, the dosage is 800 mg as tablets or 10 ml of suspension 4 times daily; in children aged 2 to 6 years, the dosage is 400 mg as tablets or 5 ml of suspension 4 times daily. The product should not be administered to children under 2 years of age, as efficacy and safety have not been established in this age group. Administration of 20 mg/kg body weight (not exceeding 800 mg) 4 times daily allows for more precise dose adjustment. Treatment should be continued for 5 days.
Specific data on suppression of Herpes simplex infections or treatment of Herpes zoster in children with normal immune function are not available.
For the treatment of Herpes zoster in immunocompromised children, intravenous administration of the drug should be considered.

Elderly
In elderly patients, total elimination of Aciclovir decreases as certain renal function parameters decline with advancing age. In elderly patients, the possibility of renal impairment should be considered, and dosage should be adjusted accordingly (see below "Renal impairment"). Elderly patients taking high oral doses of Aciclovir should maintain adequate fluid intake. Particular attention should be paid when evaluating the need for dose reduction in elderly patients with impaired renal function.

Renal impairment
Caution is recommended when administering Aciclovir to patients with impaired renal function.
Adequate hydration should be maintained.
In the treatment of Herpes simplex infections, the recommended oral dosage in patients with impaired renal function should not cause accumulation of Aciclovir above levels shown to be tolerated following intravenous administration. In patients with severe renal impairment (creatinine clearance less than 10 ml/min), the dose should be adjusted to 200 mg administered twice daily at intervals of approximately 12 hours.
In the treatment of varicella and Herpes zoster, dosage adjustment is recommended as follows: 800 mg as tablets or 10 ml of suspension twice daily at intervals of approximately 12 hours in patients with severe renal impairment (creatinine clearance less than 10 ml/min), and 800 mg as tablets or 10 ml of suspension three times daily at intervals of approximately 8 hours in patients with moderate renal impairment (creatinine clearance between 10 and 25 ml/min).

OVERDOSE
Symptoms and signs:
Aciclovir is only partially absorbed at the intestinal level.
Patients who have occasionally ingested overdoses up to 20 g of aciclovir in a single dose have generally not shown toxic effects. Accidental and repeated oral overdoses of aciclovir, lasting for several days, have been associated with gastrointestinal effects (such as nausea and vomiting) and neurological effects (headache and confusion). Intravenous overdoses of aciclovir have led to increased serum creatinine and blood urea nitrogen levels, resulting in renal failure. Neurological effects including confusion, hallucinations, agitation, seizures, and coma have been reported in association with intravenous overdose.

Treatment
Patients should be closely monitored for signs of toxicity.
Aciclovir is dialyzable. Haemodialysis significantly contributes to the removal of aciclovir from the blood and may therefore be considered as a management option in symptomatic overdose.
In case of accidental ingestion/overdose of Aciclovir Almus, contact a doctor immediately or go to the nearest hospital.
If you have any doubts about the use of Aciclovir Almus, consult your doctor or pharmacist.

UNDESIRABLE EFFECTS
Like all medicines, Aciclovir Almus can cause adverse effects, although not everyone experiences them.
The frequency categories associated with the adverse events listed below are estimates. For most events, adequate data on incidence are not available. Furthermore, the incidence of adverse events may vary depending on the indication.
The following convention has been used to classify undesirable effects by frequency: very common ≥ 1/10; common ≥1/100, <1/10; uncommon ≥1/1000, <1/100; rare ≥1/10,000, <1/1000; very rare <1/10,000.

Disorders of the haematopoietic and lymphatic system
Very rare: anaemia, leucopenia, thrombocytopenia

Immune system disorders
Rare: anaphylaxis

Psychiatric disorders and nervous system disorders
Common: headache, dizziness
Very rare: agitation, confusion, tremor, ataxia, dysarthria, hallucinations, psychotic symptoms, seizures, somnolence, encephalopathy, coma.
The above events are usually reversible and generally occur in patients with renal impairment or other predisposing factors.

Respiratory, thoracic and mediastinal disorders
Rare: dyspnoea

Gastrointestinal disorders
Common: nausea, vomiting, diarrhoea, abdominal pain

Hepatobiliary disorders
Rare: reversible increases in bilirubin and liver enzymes
Very rare: hepatitis, jaundice

Skin and subcutaneous tissue disorders
Common: pruritus, skin rashes (including photosensitivity)
Uncommon: urticaria, rapid and widespread hair loss
Skin rashes have occurred in some patients after oral administration of aciclovir, promptly resolving upon discontinuation of therapy.
Rapid and widespread hair loss has been associated with a wide range of conditions and drug use; therefore, the relationship of this event to aciclovir therapy is uncertain.
Rare: angioedema

Renal and urinary disorders
Rare: increases in blood urea nitrogen and creatinine
Very rare: acute renal failure, renal pain
Renal pain may be associated with renal failure.

General disorders and administration site conditions
Common: fatigue, fever
Following the instructions in the leaflet reduces the risk of undesirable effects.

Reporting of undesirable effects
If you experience any undesirable effect, including those not listed in this leaflet, contact your doctor or pharmacist. Undesirable effects can also be reported directly via the national reporting system at www.agenziafarmaco.gov.it/it/responsabili. Reporting adverse effects contributes to providing more information on the safety of this medicine.

EXPIRY DATE AND STORAGE
Expiry date: see the date on the packaging.
Warning: do not use the medicine after the expiry date stated on the packaging.
Storage
800 mg tablets: store in a dry place.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.
Keep the medicine out of the reach and sight of children.

COMPOSITION
ACICLOVIR ALMUS 800 mg TABLETS
One tablet contains:
Active substance: Aciclovir 800 mg
Excipients: Microcrystalline cellulose, Sodium starch glycolate, Polyvinylpyrrolidone, Magnesium stearate

ACICLOVIR ALMUS 400 mg/5 ml ORAL SUSPENSION
5 ml of oral suspension contains:
Active substance: Aciclovir 400 mg
Excipients: Sorbitol (70% non-crystallizable), Glycerol, Dispersible cellulose, Methyl p-hydroxybenzoate, Propyl p-hydroxybenzoate, Cherry flavour, Purified water.

PHARMACEUTICAL FORM AND CONTENT

• Tablets 800 mg; pack of 35 tablets of 800 mg
• 400 mg/5 ml oral suspension; 100 ml bottle

MARKETING AUTHORISATION HOLDER
ALMUS S.r.l.
Via Cesarea 11/10
16121 - Genoa (GE)

MANUFACTURER AND FINAL CONTROLLER
Special Product’s Line S.p.A.
Via Campobello, n. 15
00040 - Pomezia (RM)

ACICLOVIR ALMUS 5% - Cream
Generic medicine

COMPOSITION
One gram of cream contains:
Aciclovir 50 mg
Excipients: Tefose 1500; Glycerin; Stearic acid; Liquid paraffin; Methylparaben; purified water.

PHARMACEUTICAL FORM AND CONTENT
5% Aciclovir cream tube in a pack containing a 10 g tube of 5% topical cream

THERAPEUTIC PHARMACOLOGICAL CATEGORY
Topical antiviral chemotherapeutic agents

MARKETING AUTHORISATION HOLDER
ALMUS S.r.l.
Via Cesarea n. 11/10
16121 - Genoa

MANUFACTURER AND FINAL CONTROLLER
Special Product’s Line S.p.A.
Via Campobello 15
00040 Pomezia (RM)

THERAPEUTIC INDICATIONS
Aciclovir cream is indicated for the treatment of cutaneous Herpes simplex infections such as:

• Primary or recurrent genital herpes.
• Cold sores (herpes labialis).

CONTRAINDICATIONS
Aciclovir cream is contraindicated in patients with known hypersensitivity to aciclovir, valaciclovir, or to any of the excipients.
Generally contraindicated during pregnancy and breastfeeding (see Special warnings).

PRECAUTIONS FOR USE
No special precautions

INTERACTIONS
Inform your doctor or pharmacist if you have recently taken any other medicines, including those without a prescription.
No clinically significant interactions have been identified.

SPECIAL WARNINGS
The product is not for ophthalmic use, and application of the cream on the mucous membranes of the mouth, eyes, and vagina is not recommended, as it may cause irritation. Particular care should be taken to avoid accidental application into the eyes.
In severely immunocompromised patients (e.g. patients with AIDS or bone marrow transplant recipients), oral formulations of aciclovir should be considered. Such patients should be advised to consult their doctor regarding treatment of any infection.
Prolonged use, especially, of the product may lead to sensitization phenomena. If this occurs, treatment should be discontinued and the physician consulted.

Pregnancy
Consult your doctor or pharmacist before taking any medicine.
Aciclovir Almus should be used only when potential benefits outweigh the possibility of unknown risks. However, systemic exposure to aciclovir after topical application of aciclovir cream is very low.
A post-marketing registry on the use of aciclovir during pregnancy has provided data on pregnancy outcomes in women exposed to various formulations of aciclovir.
These observations have not shown an increased number of birth defects among subjects exposed to aciclovir compared to the general population, and all birth defects observed did not show any particular pattern or common features suggesting a single cause.

Breastfeeding
Limited data in humans indicate that the drug is excreted in breast milk after systemic administration. However, the dose received by an infant following maternal use of Aciclovir cream should be negligible.

DOSAGE, METHOD AND DURATION OF ADMINISTRATION
Aciclovir cream should be applied 5 times daily at intervals of approximately 4 hours.
Aciclovir cream should be applied to the lesions or to areas where lesions are developing as soon as possible after the onset of infection.
It is particularly important to start treatment of recurrent episodes during the prodromal phase (initial symptoms of infection, i.e. itching and/or burning and/or pain) or at the first appearance of lesions.
Treatment should continue for at least 5 days and up to a maximum of 10 days if healing has not occurred.

OVERDOSE
In case of accidental ingestion/overdose of Aciclovir cream, contact a doctor immediately or go to the nearest hospital.
If you have any doubts about the use of Aciclovir cream, consult your doctor or pharmacist.
Even if the entire contents of a 10 g tube of Aciclovir cream containing 500 mg of aciclovir are ingested, no adverse effects are expected.
Single intravenous doses up to 80 mg/kg have been accidentally administered without side effects. Aciclovir can be removed by dialysis.

UNDESIRABLE EFFECTS
Like all medicines, this product may cause undesirable effects, although not everyone experiences them.
The following convention has been used for classification of undesirable effects by frequency: very common ≥1/10, common ≥1/100 and <1/10, uncommon ≥1/1000 and <1/100, rare ≥1/10,000 and <1/1000, very rare <1/10,000.

Skin and subcutaneous tissue disorders
Uncommon: transient burning or pain after application, mild dryness, desquamation of the skin, and pruritus.
Rare: erythema, contact dermatitis after application.
Where sensitivity testing has been performed, reactivity phenomena have been shown to be related to components of the cream rather than to aciclovir.

Immune system disorders
Very rare: immediate hypersensitivity reactions including angioedema and urticaria
If adverse effects occur, it is advisable to consult your physician.
It is important to inform your doctor of the occurrence of any adverse effects not described in this leaflet.

EXPIRY DATE AND STORAGE
For the expiry date, refer to the date on the packaging.
Warning: do not use the medicine beyond the expiry date indicated on the packaging; this date refers to the product in intact packaging, correctly stored.
Storage instructions
Store at a temperature not exceeding 25°C.
Keep out of reach and sight of children.