ACICLOVIR ZENTIVA 200 mg Cpr Plq/25

Tablet.

Aciclovir.........................................................................................................................................................200 mg

For one tablet.

Excipients:

• Treatment of infections caused by viruses Herpes simplex (HSV) of the skin and mucous membranes, including initial and recurrent genital herpes (excluding neonatal HSV and severe HSV infections in immunocompromised children).
• Suppression (prevention of recurrences) of recurrent infections due to Herpes simplex in immunocompetent patients.
• Prophylaxis of infections caused by Herpes simplex in immunocompromised patients.
• Treatment of infections caused by varicella (when clinically relevant) and for the treatment of infections caused by Herpes zoster (shingles), see section 5.1. Pharmacodynamic properties.
• Prevention of recurrence of ocular HSV infections:

• epithelial keratitis after 3 recurrences per year or in the case of a known triggering factor,
• stromal keratitis and keratouveitis after 2 recurrences per year,
• in case of eye surgery.
  • Treatment of HSV keratitis and keratouveitis.

Posologygy

Table 1: Summary of dosages for all indications

 

Indication	Dosage
Treatment of cutaneous and mucosal HSV infections	Immunocompetent and immunocompromised adults 200 mg 5 times a day for 5 days	Immunocompetent and immunosuppressed children Children ≥ 2 years: 200 mg 5 times a day for 5 days Infants and children under 2 years: 100 mg 5 times daily for 5 days
Suppression of recurrent HSV infections	Immunocompetent adults 200 mg 4 times a day; 400 mg 2 times daily (treatment duration of 6-12 months)
Prophylaxis of HSV infections in immunosuppressed patients	Immunosuppressed adults 200 mg 4 times daily (treatment duration is determined by the duration of the period at risk)	Immunosuppressed children Children ≥ 2 years: 200 mg 4 times daily Infants and children under 2 years: 100 mg 4 times daily (treatment duration is determined by the duration of the period at risk)
Treatment of infections caused by varicella	Immunocompetent adults 800 mg 5 times daily for 7 days	Immunocompetent children 6 years and over: 800 mg 4 times a day for 5 days 2 to 6 years: 400 mg 4 times a day for 5 days < 2 years: 200 mg 4 times a day for 5 days
Treatment of infections due to Herpes zoster	Immunocompetent adults 800 mg 5 times daily for 7 days
Prevention of recurrences of ocular HSV infections	Immunocompetent adults · Epithelial keratitis after 3 recurrences per year, stromal keratitis and keratouveitis after 2 recurrences per year: 4 tablets of 200 mg per day, divided into 2 doses · In case of eye surgery: 4 tablets of 200 mg per day, divided into 2 doses
Treatment of ocular HSV infections	Immunocompetent adults Keratitis and keratouveitis: 10 tablets of 200 mg per day, divided into 5 doses

Table 2: Summary of dosages for patients with renal impairment

Creatinine clearance	Dosage
10-25 mL/min	Infections caused by varicella and infections due to Herpes zoster : 800 mg 3 times daily
< 10 mL/min	Infections by the herpes simplex virus herpes simplex : 200 mg 2 times per day Suppression of recurrent infections by the herpes simplex virus herpes simplex in immunocompetent patients: 200 mg 2 times daily Prophylaxis of infections by the herpes simplex virus herpes simplex in immunocompromised patients: 200 mg 2 times per day Infections by the varicella-zoster virus, including chickenpox and herpes zoster: 800 mg 2 times daily

Please refer to the section below for detailed dosage recommendations.

Treatment of herpes simplex

Adults

For the treatment of infections due to Herpes simplex, 200 mg of aciclovir should be taken 5 times daily at intervals of approximately 4 hours, not counting the nighttime dose. Treatment should continue for 5 days, but it may be extended in severe initial infections.

In severely immunocompromised patients (for example, after bone marrow transplantation) or in patients with impaired intestinal absorption, the dose may be doubled to 400 mg or, alternatively, intravenous treatment may be considered.

Treatment should start as early as possible after the onset of infection; for recurrent episodes, this should preferably be during the prodromal period or when lesions first appear.

Elderly

The possibility of renal impairment in elderly people should be considered and the dosage adjusted accordingly (see Renal impairment).

Adequate hydration of elderly patients taking high oral doses of aciclovir should be maintained.

Renal impairment

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

In the treatment of infections due to Herpes simplex in patients with impaired renal function, the recommended oral doses will not lead to accumulation of aciclovir beyond levels established as safe by intravenous infusion. However, for patients with severe renal impairment (creatinine clearance less than 10 mL/min), a dosage adjustment to 200 mg 2 times daily at intervals of approximately 12 hours is recommended.

Paediatric population

For the treatment of infections due to Herpes simplex, children aged 2 years and older should receive adult doses, and infants and children under 2 years should receive half the adult dose.

For the treatment of neonatal HSV infections, intravenous aciclovir is recommended.

Other pharmaceutical forms/strengths may be more appropriate for administration to this population.

Suppression (prevention of recurrences) of recurrent infections due to Herpes simplex in immunocompetent patients

Adults

For the suppression of infections due to Herpes simplex in immunocompetent patients, 200 mg of aciclovir should be taken 4 times daily at intervals of approximately 6 hours.

Many patients can be managed adequately with a dose of 400 mg of aciclovir taken 2 times a day at intervals of approximately 12 hours.

Dose titration up to 200 mg of aciclovir taken 3 times a day at intervals of approximately 8 hours, or even 2 times a day at intervals of approximately 12 hours, may prove effective.

Some patients may present with infections despite taking the treatment at a total daily dose of 800 mg of aciclovir.

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

Elderly

The possibility of renal impairment in elderly people should be considered and the dosage adjusted accordingly (see Renal impairment).

Adequate hydration of elderly patients taking high oral doses of aciclovir should be maintained.

Renal impairment

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

In the prophylaxis of HSV infections in patients with impaired renal function, the recommended oral doses will not lead to an accumulation of aciclovir beyond the levels established as safe with intravenous infusion. However, for patients with severe renal impairment (creatinine clearance less than 10 mL/min), dose adjustment to 200 mg 2 times a day at intervals of approximately 12 hours is recommended.

Paediatric population

No data are available on the suppression of HSV infections in immunocompetent children.

Prophylaxis of herpes simplex in immunocompromised patients

Adults

For the prophylaxis of HSV infections in immunocompromised patients, 200 mg of aciclovir should be taken 4 times a day at intervals of approximately 6 hours.

In severely immunocompromised patients (for example, after bone marrow transplantation) or in patients with impaired intestinal absorption, the dose may be doubled to 400 mg or, alternatively, intravenous treatment may be considered.

The duration of prophylactic administration is determined by the duration of the period at risk.

Elderly

The possibility of renal impairment in elderly people should be considered and the dosage adjusted accordingly (see Renal impairment).

Adequate hydration of elderly patients taking high oral doses of aciclovir should be maintained.

Renal impairment

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

In the prophylaxis of HSV infections in patients with impaired renal function, the recommended oral doses will not lead to an accumulation of aciclovir beyond the levels established as safe with intravenous infusion. However, for patients with severe renal impairment (creatinine clearance less than 10 mL/min), dose adjustment to 200 mg 2 times a day at intervals of approximately 12 hours is recommended.

Paediatric population

For the prophylaxis of HSV infections in immunocompromised children aged 2 years and over, adult doses should be administered, and infants and children under 2 years should receive half the adult dose.

Other pharmaceutical forms/strengths may be more appropriate for administration to this population.

Treatment of varicella and infections due to Herpes zoster

Adults

For the treatment of varicella infections and infections due to Herpes zoster, 800 mg of aciclovir should be taken 5 times a day at intervals of approximately 4 hours, without considering the night-time dose. Treatment should continue for 7 days.

In severely immunocompromised patients (for example, after bone marrow transplantation) or in patients with impaired intestinal absorption, intravenous treatment may be considered.

Treatment should begin as early as possible after the onset of infection. Results are better if treatment is initiated as soon as possible after the appearance of the skin rash.

Elderly

The possibility of renal impairment in elderly people should be considered and the dosage adjusted accordingly (see Renal impairment).

Adequate hydration of elderly patients taking high oral doses of aciclovir should be maintained.

Renal impairment

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

In the treatment of varicella infections and infections due to Herpes zoster, it is recommended to adjust the dose to 800 mg 2 times a day, at intervals of approximately 12 hours, for patients with severe renal impairment (creatinine clearance less than 10 mL/min) and to 800 mg 3 times a day, at intervals of approximately 8 hours, for patients with moderate renal impairment (creatinine clearance between 10 and 25 mL/min).

Paediatric population

For the treatment of varicella infections in children aged:

• 6 years and over: 800 mg of aciclovir 4 times a day

• 2 to < 6 years: 400 mg of aciclovir 4 times a day

• Under 2 years: 200 mg of aciclovir 4 times a day

The dose may be calculated more precisely at 20 mg of aciclovir/kg body weight (not exceeding 800 mg) 4 times a day. Treatment should continue for 5 days.

No data are available on the treatment of infections due to Herpes zoster in immunocompetent children.

Other pharmaceutical forms/strengths may be more appropriate for administration to this population.

Prevention of recurrences of ocular HSV infections

Adults

For the prevention of recurrences of epithelial keratitis after 3 recurrences per year, stromal keratitis and keratouveitis after 2 recurrences per year, 4 tablets of 200 mg per day should be taken, divided into 2 doses.

Treatment will be reassessed at intervals of 6 to 12 months, in order to evaluate any possible change related to the natural course of the disease.

In case of eye surgery, 4 tablets of 200 mg per day should be taken, divided into 2 doses.

Treatment should be initiated as soon as possible after the onset of an infection. In the case of recurrent episodes, treatment initiation should preferably take place during the prodromal phase or upon the appearance of the first lesions.

Elderly

The possibility of renal impairment in elderly people should be considered and the dosage adjusted accordingly (see Renal impairment).

Adequate hydration of elderly patients taking high oral doses of aciclovir should be maintained.

Renal impairment

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

In the prophylaxis of HSV infections in patients with impaired renal function, the recommended oral doses will not lead to an accumulation of aciclovir beyond the levels established as safe with intravenous infusion. However, for patients with severe renal impairment (creatinine clearance less than 10 mL/min), dose adjustment to 200 mg 2 times a day at intervals of approximately 12 hours is recommended.

Paediatric population

In children over 6 years, the dosage is the same as in adults.

Treatment of ocular HSV infections

Adults

For the treatment of keratitis and keratouveitis, 10 tablets of 200 mg per day should be taken, divided into 5 doses.

Treatment should be initiated as soon as possible after the onset of an infection. In the case of recurrent episodes, treatment initiation should preferably take place during the prodromal phase or upon the appearance of the first lesions.

Elderly

The possibility of renal impairment in elderly people should be considered and the dosage adjusted accordingly (see Renal impairment).

Adequate hydration of elderly patients taking high oral doses of aciclovir should be maintained.

Renal impairment

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

For patients with severe renal impairment (creatinine clearance less than 10 mL/min), dose adjustment to 200 mg 2 times a day at intervals of approximately 12 hours is recommended.

Paediatric population

In children over 6 years, the dosage is the same as in adults.

Aciclovir tablets, suspensions and powders for solution for injection (IV) are contraindicated in patients with known hypersensitivity to aciclovir, valaciclovir or any of the excipients.

Severe cutaneous adverse reactions (SCARs)

Cases of acute generalised exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS), which may be life-threatening or lead to death, toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) have been reported in patients treated with aciclovir.

Patients must be informed of the signs and symptoms of severe cutaneous adverse reactions and must seek medical advice immediately if signs or symptoms suggestive of them appear. If signs and symptoms suggestive of these reactions appear, treatment with aciclovir must be stopped immediately and another treatment considered (where appropriate). If the patient has developed a severe cutaneous adverse reaction such as SJS, TEN, DRESS or AGEP with the use of aciclovir, treatment with aciclovir or valaciclovir must under no circumstances be resumed in this patient.

Special warnings

The diagnosis of primary herpetic infection is a clinical probability diagnosis.

Precautions for use

Patient hydration status: adequate fluid intake must be ensured for patients at risk of dehydration, in particular elderly people, as well as in patients receiving aciclovir intravenously or high oral doses of aciclovir.

Patients with renal impairment and elderly patients: as aciclovir is eliminated via the kidneys, the dose must be adjusted according to creatinine clearance (see section Dosage and administration).

Elderly patients are likely to have reduced renal function and therefore a dose reduction of aciclovir should be considered in these patients.

Concomitant use of other nephrotoxic medicinal products increases the risk of renal impairment.

Neurological disorders (see section Adverse effects) are likely to occur more frequently in patients with renal impairment and in elderly patients whose renal function is potentially reduced.

Elderly and/or renally impaired patients must be closely monitored in order to identify these neurological adverse reactions, which are generally reversible after discontinuation of treatment (see section Adverse effects).

Prolonged treatment or repeated administrations of aciclovir in severely immunocompromised patients may lead to the selection of virus strains with reduced sensitivity to aciclovir, which may result in no response to continued aciclovir treatment (see section Pharmacodynamics).

The occurrence of renal pain should prompt consideration of renal impairment and discontinuation of treatment.

Do not give to children under 6 years, due to the risk of aspiration.

Associations to be taken into account

+ Other nephrotoxic medicinal products

Risk of increased nephrotoxicity

Concomitant use of medicinal products with intrinsic renal toxicity increases the risk of nephrotoxicity. If such a combination is necessary, biological monitoring of renal function must be reinforced.

Aciclovir is eliminated mainly unchanged in the urine by active renal tubular secretion.
Any medicinal product administered simultaneously that competes for this mechanism may increase the plasma concentrations of aciclovir.

Probenecid and cimetidine increase the AUC of aciclovir through this mechanism and reduce the renal clearance of aciclovir.

Similarly, increases in the plasma AUCs of aciclovir and of the inactive metabolite of mycophenolate mofetil, an immunosuppressive agent used in transplant patients, have been observed when these medicinal products are co-administered.

However, no dose adjustment is necessary because of the wide therapeutic index of aciclovir.

Increases of about 50% in the AUC of total theophylline administered were shown in a clinical study conducted in 5 male subjects during concomitant administration of aciclovir. Determination of plasma concentrations is recommended when co-administered with aciclovir.

Pregnancy

Studies performed in animals have demonstrated a teratogenic effect in a single species and at very high dosage.

A post-marketing pregnancy registry documented pregnancy outcomes of women exposed to aciclovir (regardless of the form used). Registry data did not show an increase in the number of malformations in women exposed to aciclovir compared with the general population, and no malformation showed an exceptional or recurrent character suggesting a common cause.

However, only epidemiological studies would allow verification of the absence of risk.

In standard internationally recognised tests, systemic administration of aciclovir did not show teratogenic or embryotoxic effects in rabbits, rats or mice. In non-standardised tests in rats, fetal abnormalities were observed but only following high subcutaneous doses causing maternal toxicity. The clinical relevance of these results is unknown.

Use of aciclovir during pregnancy should only be considered if the expected benefits outweigh the potential risks incurred.

No study permits administration of aciclovir in recurrent genital herpes in pregnant women, particularly at the end of pregnancy.

Breast-feeding

Following oral administration of 200 mg of aciclovir five times daily, aciclovir was detected in breast milk at concentrations ranging from 0,6 to 4,1 times the corresponding plasma levels. These concentrations could potentially expose breastfed infants to aciclovir doses of up to 0,3 mg/kg/day. Caution is therefore advised when aciclovir is administered to women who are breastfeeding.

In severe conditions requiring maternal systemic treatment, breastfeeding must be avoided. In other cases, where possible, preference should be given to topical treatment, with which breastfeeding is possible.

Fertility

See clinical studies.

The patient's clinical condition and the profile of neuropsychiatric adverse reactions to aciclovir must be taken into account when considering the patient's ability to drive vehicles and use machines.

No study has been conducted to evaluate the effects of aciclovir on the ability to drive vehicles or use machines.

The frequency categories assigned to the adverse reactions below were established on the basis of clinical trial data to classify adverse reactions, bearing in mind that this incidence may vary depending on the indication.

The frequency of other adverse reactions could not be estimated from spontaneous reports due to the absence of appropriate data for calculating their frequency.

The following convention has been used for classifying undesirable effects according to their 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).

• Blood and lymphatic system disorders

Frequency not determined: Thrombocytopenia, leukopenia.

• Immune system disorders

Frequency not determined: Anaphylactic reactions.

• Nervous system disorders

Very common: Headaches

Common: Dizziness.

Disturbances of balance, ataxia and dysarthria may be associated or occur in isolation and indicate a cerebellar syndrome.

Sometimes severe neurological disorders that may present as an encephalopathy picture and include confusion, agitation, tremors, myoclonus, convulsions, hallucinations, psychosis, drowsiness, coma are possible.

Complete regression is usual upon discontinuation of treatment.

These neurological signs are usually observed in renally impaired patients who received doses higher than the recommended dosage or in elderly patients (see section Warnings and precautions). However, they may also be observed in the absence of these predisposing factors. The presence of these symptoms should prompt a search for an overdose (see section Overdose).

• Respiratory, thoracic and mediastinal disorders

Frequency not determined: Dyspnea.

• Gastrointestinal disorders

Common: Nausea, vomiting, diarrhea, abdominal pain.

• Hepatobiliary disorders

Common: Reversible increases in bilirubin and serum liver enzymes.

Frequency not determined: Acute hepatic injury

• Skin and subcutaneous tissue disorders

Common: pruritus

Uncommon: skin rash, urticaria

Very rare: Toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), acute generalised exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS) (see section Warnings and precautions).

Isolated cases of Quincke's oedema

• Renal and urinary disorders

Common: Increased blood urea and creatinine.

Frequency not determined: acute renal failure, particularly in elderly or renally impaired subjects in case of overdose, renal pain.

Renal pain may be associated with renal failure (see section Warnings and precautions).

• General disorders and administration site conditions

Frequency not determined: Fatigue, fever.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reaction via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Centres of Pharmacovigilance - Website: https://signalement.social-sante.gouv.fr.

Signs and symptoms

By oral route, intestinal absorption is low. However, in renally impaired patients treated with doses of aciclovir not adapted to renal function, alterations of consciousness ranging from mental confusion with hallucinations to coma have been described. The outcome has always been favourable after discontinuation of treatment and possible haemodialysis.

Patients have ingested single doses of up to 20 g of aciclovir, generally without toxic effect. Accidental and repeated overdoses of oral aciclovir over several days have been associated with gastrointestinal (such as nausea and vomiting) and neurological (headache and confusion) effects.

Intravenous administration of a single dose of 80 mg/kg caused no undesirable effects.

Aciclovir is dialysable.

An intravenous overdose of aciclovir led to an increase in serum creatinine, blood urea and subsequently to renal failure. Neurological effects such as confusion, hallucinations, agitation, convulsions and coma have been described associated with the overdose.

Treatment

Patients must be closely monitored in order to detect any signs of toxicity.

Haemodialysis significantly increases the elimination of aciclovir from the blood circulation and may therefore be considered as a management option in case of symptomatic overdose.

Pharmacotherapeutic class: DIRECT-ACTING ANTIVIRALS, nucleosides and nucleotides excluding reverse transcriptase inhibitors, ATC code: J05AB01

Aciclovir is a specific inhibitor of herpes viruses, with in vitro activity against viruses Herpes simplex (HSV) types 1 and 2, Varicella-zoster (VZV).

Aciclovir, after being phosphorylated to aciclovir triphosphate, inhibits viral DNA synthesis. The first step of phosphorylation is carried out solely by a specific viral enzyme.

For the HSV and VZV viruses, this is a viral thymidine kinase which is present only in cells infected by the virus.

Phosphorylation of aciclovir monophosphate to di- and triphosphate is carried out by cellular kinases. Aciclovir triphosphate is a selective competitive inhibitor of viral DNA polymerase, and incorporation of this nucleoside analogue stops elongation of the DNA chain, thereby interrupting viral DNA synthesis. Viral replication is therefore blocked.

Due to its dual selectivity, aciclovir does not interfere with the metabolism of healthy cells.

Study of a large number of clinical isolates during curative or preventive treatment with aciclovir has shown that a decrease in sensitivity to aciclovir is extremely rare in immunocompetent subjects. In immunodeficient subjects (such as organ or bone marrow transplant recipients, subjects receiving anticancer chemotherapy and subjects infected with the human immunodeficiency virus (HIV)), a decrease in sensitivity has occasionally been demonstrated.

The rare resistances observed are generally due to a deficient viral thymidine kinase and result in lower virulence. A few cases of decreased sensitivity to aciclovir have been observed following a modification either of thymidine kinase or of viral DNA polymerase. The virulence of these viruses does not appear to be modified.

Clinical studies

There is no information on the effect of oral or injectable (IV) forms of aciclovir on female fertility.

In a study of 20 male patients with normal sperm counts, aciclovir administered orally at doses of up to 1 g per day for a duration of up to 6 months did not show any clinically significant effect on sperm count, motility and morphology.

Clinical efficacy and safety

Studies have shown that early treatment of herpes zoster with aciclovir has a beneficial effect on pain and may reduce the incidence of post-herpetic neuralgia (pain associated with herpes zoster), see section Indications. Therapeutic indications.

Absorption

Aciclovir is only partially absorbed by the intestine. The mean bioavailability of oral forms ranges between 10 and 20 %.

After doses of 200 mg of aciclovir administered every four hours in adults, mean steady-state maximum concentrations (Cssmax) reach 0,7 µg/mL (3,1 µM).

Following administration of doses of 400 mg and 800 mg every four hours in adults, a less than proportional increase in dose Cssmax was observed, with levels reaching 1,2 and 1,8 µg/mL (5,3 and 8 µM), respectively.

Distribution

The mean volume of distribution of 26 L indicates that aciclovir is distributed throughout the total body water. The apparent values after oral administration (Vd/F) ranging from 2,3 to 17,8 L/kg.

Aciclovir diffuses into tissues including brain, kidneys, lungs, liver, muscles, vaginal secretions, and herpetic vesicular fluid.

Aciclovir is weakly bound to plasma proteins (9 to 33 %), and drug interactions involving displacement of aciclovir from its binding sites are not expected.

Levels in the cerebrospinal fluid are approximately 50 % of steady-state plasma concentrations.

Biotransformation

Aciclovir is mainly excreted unchanged by the kidney. The 9-(carboxymethoxymethyl) guanine, the main metabolite of aciclovir, represents approximately 10-15% of the dose excreted in urine.

Elimination

Mean systemic exposure (AUC0-∞) to aciclovir ranges between 1,9 and 2,2 µg*h/mL after a dose of 200 mg.

In adults, the terminal plasma half-life of aciclovir after oral administration of aciclovir ranges between 2,8 and 4,1 hours.

The renal clearance of aciclovir (CLr=14,3 L/h)  is substantially higher than creatinine clearance, indicating that tubular secretion, in addition to glomerular filtration, contributes to renal elimination of the drug. The half-life and total clearance of aciclovir depend on renal function. Therefore, dose adjustment is recommended for patients with renal impairment.

The terminal plasma half-life in newborns (0 to 3 months) treated with doses of 10 mg/kg administered by one-hour infusion every 8 hours was 3,8 hours.

In elderly subjects, total body clearance decreases with increasing age and is associated with a decrease in creatinine clearance, although there is little change in terminal plasma half-life.

In patients with chronic renal failure, the mean terminal half-life was 19,5 hours. The mean half-life of aciclovir was 5,7 hours during haemodialysis. Plasma aciclovir levels decreased by approximately 60 % during dialysis.

3 years.

Store in the outer packaging, protected from moisture.

Store at a temperature not exceeding +25°C.

No special requirements.

List I

Marketing authorisation (AMM)

CIP 3400937814812 (Plq/25).

Price:

8,12 euros (Plq/25).

Social Security reimbursement at 65%.
Collection.