Valganvir

Valganciclovir

Film-coated tablets

Pink, convex oval film-coated tablets.

1 tablet contains:
Active substance: valganciclovir – 450 mg (in the form of valganciclovir hydrochloride – 496.3 mg);
Auxiliary substances: succinic acid, mannitol, povidone, crospovidone, sodium stearyl fumarate, microcrystalline cellulose;
Coating composition: Opadry 15B24005 pink (hydroxypropylmethylcellulose 3 MPas, hydroxypropylmethylcellulose 6 MPas, titanium dioxide (E171), macrogol (polyethylene glycol), red iron oxide (E172), polysorbate 80).

Antivirals for systemic use. Nucleosides and nucleotides excl. reverse transcriptase inhibitors.

J05AB14

Mechanism of action
After oral administration, valganciclovir is rapidly and extensively metabolised to ganciclovir by intestinal and hepatic esterases. Ganciclovir is a synthetic analogue of 2′-deoxyguanosine and inhibits replication of herpes viruses in vitro and in vivo Human viruses sensitive to ganciclovir include cytomegalovirus (CMV), herpes simplex viruses type 1 and 2 (Herpes simplex), human herpes virus types 6, 7 and 8 (HHV-6, HHV-7, HHV-8), Epstein-Barr virus, varicella-zoster virus) and hepatitis B virus.

In CMV-infected cells, ganciclovir is initially phosphorylated to ganciclovir monophosphate by the viral protein kinase, pUL97. Further phosphorylation occurs by cellular kinases to produce ganciclovir triphosphate, which is then slowly metabolised intracellularly. Triphosphate metabolism has been shown to occur in HSV- and CMV-infected cells with half-lives of 18 and between 6 and 24 hours respectively, after the removal of extracellular ganciclovir. As the phosphorylation is largely dependent on the viral kinase, phosphorylation of ganciclovir occurs preferentially in virus-infected cells.

The virustatic activity of ganciclovir is due to inhibition of viral DNA synthesis by:
a) competitive inhibition of incorporation of deoxyguanosine-triphosphate into DNA by viral DNA polymerase,
b) incorporation of ganciclovir triphosphate into viral DNA causing termination of, or very limited, further viral DNA elongation.

Antiviral activity
The in-vitro antiviral activity, measured as IC50 of ganciclovir against CMV, is in the range of 0.08 μM (0.02 μg/ml) to 14 μM (3.5 μg/ml).
The clinical antiviral effect of valganciclovir has been demonstrated in the treatment of AIDS patients with newly diagnosed CMV retinitis. CMV shedding was decreased in urine from 46% (32/69) of patients at study entry to 7% (4/55) of patients following four weeks of valganciclovir treatment.

Clinical efficacy
The use of valganciclovir makes it possible to obtain the same systemic concentration of ganciclovir as the use of ganciclovir at recommended doses (intravenously), effective in the treatment of CMV retinitis. It has been shown that ganciclovir AUC correlates with progression of CMV retinitis over time.

The incidence of CMV disease during the first 6 months post-transplant was 12.1% in patients receiving valganciclovir at a dose of 900 mg/day and 15.2% in patients receiving oral ganciclovir at a dose of 1 g 3 times/day starting within 10 days of transplantation until Day 100 post-transplant. The incidence of acute rejection in the first 6 months was 29.7% in patients randomized to valganciclovir compared with 36.0% in the oral ganciclovir arm.
Prolongation of CMV prophylaxis by valganciclovir up to Day 200 post-transplant in high-risk kidney transplant patients in the first 12 months post-transplant had an advantage over 100-day treatment in terms of prevention of CMV disease.

Viral resistance
Virus resistant to ganciclovir can arise after chronic dosing with valganciclovir by selection of mutations in the viral kinase gene (UL97) responsible for ganciclovir monophosphorylation and/or the viral polymerase gene (UL54). In clinical isolates, seven canonical UL97 substitutions, M460V/I, H520Q, C592G, A594V, L595S, C603W are the most frequently reported ganciclovir resistance-associated substitutions. Viruses containing mutations in the UL97 gene are resistant to ganciclovir alone, whereas viruses with mutations in the UL54 gene are resistant to ganciclovir but may show cross-resistance to other antivirals that also target the viral polymerase and vice versa.

Treatment of CMV retinitis
Genotypic analysis of CMV in polymorphonuclear leucocytes has shown that 2.2%, 6.5%, 12.8%, and 15.3% contain UL97 mutations after 3, 6, 12 and 18 months, respectively, of valganciclovir treatment.

Valganvir is indicated for the induction and maintenance treatment of cytomegalovirus (CMV) retinitis in adult patients with acquired immunodeficiency syndrome (AIDS).

Valganvir is indicated for the prevention of CMV disease in CMV-negative adults and children (aged from birth to 18 years) who have received a solid organ transplant from a CMV-positive donor.

Strict adherence to dosage recommendations is essential to avoid overdose.

Standard dosing schedule
Valganciclovir is rapidly and extensively metabolised to ganciclovir after oral dosing. Oral valganciclovir 900 mg (two 450 mg tablets) is therapeutically equivalent to intravenous ganciclovir at a dose of 5 mg/kg twice a day.
Valganvir should be taken orally preferably with meals.

Warnings and precautions before use
Do not break or crush tablets. Valganciclovir is considered to be a potential teratogenic and carcinogenic agent for humans. Care should be taken with broken tablets (see Section Special warnings and precautions). Avoid direct contact of broken or crushed tablets with skin or mucous membranes. In case of such a contact wash the contact area thoroughly with soap and water, rinse the eyes with sterile water or light water if sterile water is not available.

Treatment of CMV retinitis in adults

Induction therapy of CMV retinitis
In patients with active CMV retinitis, the recommended dose of valacyclovir is 900 mg (two 450 mg tablets) 2 times a day for 21 days, if possible, during meals. Prolonged induction therapy increases the risk of myelotoxicity (see Section Special warnings and precautions).

Supporting therapy of CMV retinitis
After induction therapy or in patients with inactive CMV retinitis, the recommended dose is 900 mg (two 450 mg tablets) once a day, if possible, during meals. If the course of retinitis worsens, it is possible to repeat the course of induction therapy; however, the possibility of developing resistance to antiviral therapy should be taken into account.

Paediatric population
The safety and efficacy of CMV retinitis treatment in paediatric population have not been studied.

Prevention of CMV infection in solid organ transplantation

Adult patients
For kidney transplant patients, the recommended dose is 900 mg (two 450 mg tablets) once daily, starting within 10 days post-transplantation and continuing until 100 days post-transplantation. Prophylaxis may be continued until 200 days post-transplantation.

For patients who have received a solid organ transplant other than kidney, the recommended dose is 900 mg (two 450 mg tablets) once daily, starting within 10 days post-transplantation and continuing until 100 days post-transplantation.

Tablets should be taken orally with meals.

Paediatric population
To prevent CMV infection in paediatric solid organ transplant patients aged 4 months to 16 years, it is recommended to take valganciclovir once a day. The recommended paediatric dose is based on body surface area (BSA) and creatinine clearance (Clcr) derived from the modified Schwartz formula.

Paediatric Dose (mg) = 7 x BSA x Clcr
If the calculated Schwartz creatinine clearance exceeds 150 mL/min/1.73 m², then a maximum value of 150 mL/min/1.73 m² should be used in the equation:

Mosteller BSA (m²)

Schwarz Clcr (mL/min)/1.73 m²)

Where k value is:
0.45 for patients aged 4 months to one year,
0.45 for patients aged one to 2 years (recommended k value = 0.45, instead of the accepted k value = 0.55),
0.55 for boys aged 2 to 13 years and girls aged 2 to 16 years,
0.7 for boys aged 13 to 15 years.

The k values provided are based on the Jaffe method of measuring serum creatinine and may require correction when fermentation methods are used.

For paediatric kidney transplant patients, the recommended once daily mg dose (7 x BSA x Clcr) should start within 10 days post-transplantation and continue until 200 days post-transplantation.

For paediatric patients who have received a solid organ transplant other than kidney, the recommended once daily mg dose (7x BSA x Clcr) should start within 10 days post-transplantation and continue until 100 days post-transplantation. Taking into account that the minimum divisible dose of the medicinal product is 25 mg (0.5 ml) all calculated doses should be rounded to the nearest 25 mg increment for the actual deliverable dose. If the calculated dose exceeds 900 mg, a maximum dose of 900 mg should be administered. The oral solution is the preferred formulation since it provides the ability to administer a dose calculated according to the formula above. However, valganciclovir film-coated tablets may be used if the calculated doses are within 10% of available 450 mg tablet doses. For example, if the calculated dose is between 405 mg and 495 mg, one 450 mg tablet may be taken.

It is recommended to monitor serum creatinine levels regularly and consider changes in height and body weight and adapt the dose as appropriate during the prophylaxis period.

Special dosage instructions

Patients with renal impairment
Serum creatinine levels or estimated creatinine clearance (Clcr) should be monitored carefully. Dosage adjustment is required according to creatinine clearance, as shown in the table below.

An estimated creatinine clearance (ml/min) can be related to serum creatinine by the following formulae:

for males = (140 – age [years]) x (body weight [kg])

         (72) x (0.011 x serum creatinine [µmol/l]);

for females = 0.85 x male value.

Patients undergoing haemodialysis
For patients on haemodialysis (Clcr < 10 ml/min) a dose recommendation cannot be given. Thus, valganciclovir should not be used in these patients.

Patients with hepatic impairment
Safety and efficacy of valganciclovir have not been established in patients with hepatic impairment.

Paediatric population
Dosing of paediatric SOT patients is individualized based on a patient’s renal function, together with body surface area.

Elderly patients
Safety and efficacy have not been established in this patient population.

Patients with severe leukopenia, neutropenia, anaemia, thrombocytopenia and pancytopenia

Treatment should not be started if the absolute number of neutrophils is less than 500 cells/ml or the number of platelets is less than 25,000 cells/ml, as well as if hemoglobin level is below 80 g/l (see Section Special warnings and precautions for use). If there is a significant deterioration of blood cell counts during therapy, treatment with haematopoietic growth factors and/or dose interruption should be considered.

Clinical study data
Valganciclovir is a prodrug of ganciclovir, which is rapidly and extensively metabolised to ganciclovir after oral administration. The undesirable effects known to be associated with ganciclovir use can be expected to occur with valganciclovir. All of the adverse drug reactions observed in clinical studies have been previously observed with ganciclovir.

In adult patients treated with valganciclovir the most frequent adverse drug reactions are neutropenia, anaemia and diarrhea.

Valganciclovir is associated with a higher risk of diarrhea compared to intravenous ganciclovir. In addition, taking valganciclovir is associated with a higher risk of neutropenia and leukopenia compared with oral ganciclovir.

Severe neutropenia (ANC <500/μL) is reported more frequently in AIDS patients with CMV retinitis treated with valganciclovir than in solid organs recipients.

Side effects incidence rate classification: very common (≥ 1/10), common (≥ 1/100, but < 1/10), uncommon (≥ 1/1000, but < 1/100), rare (≥ 1/10000, but < 1/1000).The following undesirable effects are possible when using valacyclovir:

Infections and infestations: common – oral candidiasis, sepsis (bacteremia, viremia), cellulite, urinary tract infections.

Blood and lymphatic disorders: very common – (severe) neutropenia, anemia; common – severe anemia, (severe) thrombocytopenia, (severe) leukopenia, (severe) pancytopenia; uncommon – bone marrow depression; rarely – aplastic anemia.

Immune system disorders: uncommon – anaphylactic reaction.

Metabolic and nutrition disorders: often – decreased appetite, anorexia.

Psychiatric disorders: common – depression, anxiety, confusion, pathological thinking; uncommon – arousal, psychotic disorder, hallucination.

Nervous system disorders: common – headache, insomnia, impaired taste perception, hypesthesia, paresthesia, peripheral neuropathy, dizziness, convulsions; uncommon – tremor.

Eye disorders: common – macular edema, retinal detachment, vitreous floaters, eye pain; uncommon – eye disorder, conjunctivitis.

Ear and labyrinth disorders: common – ear pain; uncommon – deafness.

Cardiac disorders: uncommon – arrhythmia.

Vascular disorders: uncommon – hypotension.

Respiratory, thoracic and mediastinal disorders: very common – dysponoea; common – cough.

Gastrointestinal disorders: very common – diarrhea; common – nausea, vomiting, abdominal pain, abdominal pain upper, dyspepsia, constipation, flatulence, dysphagia; uncommon – bloating, ulcerative stomatitis, pancreatitis.

Hepato-biliary disorders: common – (severe) liver dysfunction, increased blood alkaline phosphatase, increased AST level; uncommon – increased ALT level.

Skin and subcutaneous tissue disorders: common – dermatitis, night sweats, itching; uncommon – alopecia, urticaria, dry skin.

Musculoskeletal and connective tissue disorders: common – back pain, myalgia, arthralgia, muscle spasms.

Renal and urinary disorders: common – decreased renal creatinine clearance, impaired renal function; uncommon – hematuria, renal failure.

Reproductive system and breast disorders: uncommon – infertility male.

General disorders and administration site conditions: common – fatigue, fever, chills, pain, chest pain, malaise, weakness.

Severe thrombocytopenia may be associated with potentially life-threatening bleeding.

Retinal detachment has only been reported in HIV patients treated with valganciclovir for CMV retinitis.

Paediatric population
The most frequently reported adverse reactions on treatment in paediatric clinical trials were diarrhoea, nausea, neutropenia, leukopenia and anaemia.

In solid organ transplant patients, the overall safety profile was similar in paediatric patients as compared to adults. However, some adverse reactions, such as upper respiratory tract infections, fever, abdominal pain and urination disorder, which may be characteristic of the pediatric population, have been reported with a higher frequency in paediatric patients than in adults. Neutropenia was reported with slightly higher incidence in the two studies conducted in paediatric solid organ transplant patients as compared to adults, but there was no correlation between neutropenia and infectious adverse events in the paediatric population.

In kidney transplant paediatric patients, prolongation of valganciclovir exposure up to 200 days was not associated with an overall increase in the incidence of adverse events. The incidence of severe neutropenia (ANC < 500/µL) was higher in paediatric kidney patients treated until Day 200 as compared to paediatric patients treated until Day 100 and as compared to adult kidney transplant patients treated until Day 100 or Day 200 (see Section Special warnings and precautions).

Only limited data are available in neonates or infants with symptomatic congenital CMV infection treated with valganciclovir, however the safety appears to be consistent with the known safety profile of valganciclovir/ganciclovir.

If any of the undesirable effects listed in the instructions worsen, or you notice any other undesirable effects not listed in the instructions, inform your doctor about it.

Valganvir is contra-indicated in patients with hypersensitivity to valganciclovir, ganciclovir or to any of the auxiliary substances of the medicinal product.
Due to the similar chemical structure of valacyclovir, acyclovir and valacyclovir, cross-sensitivity reactions to these medications are possible. The drug is contra-indicated in patients with hypersensitivity to acyclovir and valacyclovir.

Valganvir is contra-indicated during pregnancy and breastfeeding, as well as for men wishing to conceive a child (see Section Administration during pregnancy and breast-feeding).

If taking a larger dose than prescribed by your doctor, immediately contact specialists to provide timely medical care!

Overdose of valganciclovir
In one adult patient, the use of the medication for several days at doses not less than 10 times higher than recommended for him, taking into account kidney damage (decreased creatinine clearance), marrow depression (medullary aplasia) developed with a fatal outcome.

It is expected that an overdose of valganciclovir could possibly result in increased renal toxicity.
Haemodialysis and hydration may be of benefit in reducing blood plasma levels in patients who receive an overdose of valganciclovir.

Overdose of intravenous ganciclovir
Reports of overdoses with intravenous ganciclovir have been received from clinical trials and during post-marketing experience. In some of these cases no adverse events were reported. The majority of patients experienced one or more of the following adverse events:
Haematological toxicity (pancytopenia, bone marrow failure, medullar aplasia, leukopenia, neutropenia, granulocytopenia).
Hepatotoxicity (hepatitis, liver function disorder).
Renal toxicity (worsening of haematuria in a patient with pre-existing renal impairment, acute kidney injury, elevated creatinine).
Gastrointestinal toxicity (abdominal pain, diarrhoea, vomiting).
Neurotoxicity (generalized tremor, seizure).

Medicinal products interactions with valganciclovir
In-vivo drug interaction studies with valganciclovir have not been performed. Since valganciclovir is extensively and rapidly metabolised to ganciclovir; drug interactions associated with ganciclovir will be expected for valganciclovir.

Medicinal products interactions with ganciclovir
Imipenem-cilastatin: seizures have been reported in patients taking imipenem-cilastatin and ganciclovir concomitantly. These medications should not be used concomitantly unless the potential benefits outweigh the potential risks (see Section Special warnings and precautions for use).

Probenecid: probenecid given with oral ganciclovir resulted in statistically significantly decreased renal clearance of ganciclovir by 20% leading to statistically significantly increased exposure (AUC) by 40%. These changes were consistent with a mechanism of interaction involving competition for renal excretion. Patients taking probenecid and valganciclovir concomitantly should be closely monitored for ganciclovir toxicity.

Trimethoprim: no clinically significant pharmacokinetic interactions have been reported with the simultaneous use of trimethoprim and ganciclovir. However, an increase in toxicity is possible, since myelosuppressive action has been established for both medicinal products, and therefore both medications should be used concomitantly only when the expected benefits outweigh the potential risks.

Mycophenolate mofetil: since both mycophenolate mofetil and ganciclovir could possibly result in neutropenia and leukopenia, patients should be monitored for increased intensity of adverse events.

Stavudine: no statistically significant pharmacokinetic interaction was observed with concomitant administration of stavudine and oral ganciclovir.

Zidovudine: when administered simultaneously with oral ganciclovir, it may lead to slightly, but statistically significantly increased zidovudine exposure (AUC) by 17%. In addition, there is a tendency, although statistically unreliable, to decrease the concentrations of ganciclovir. As both zidovudine and ganciclovir have the potential to cause neutropenia and anaemia some patients may not tolerate concomitant therapy at full dosage.

Didanosine: didanosine plasma concentrations were found to be consistently raised with simultaneous intravenous and oral administration of ganciclovir. With oral administration at a dose of 3 g and 6 g daily, an increase in the AUC of didanosine from 84% to 124% was observed, and at intravenous doses of 5 and 10 mg/kg/day, an increase in the AUC of didanosine ranging from 38 to 67% has been observed. There was no significant effect on ganciclovir concentrations. Patients should be closely monitored for didanosine toxicity.

Other antiretrovirals: when clinically relevant concentrations of ganciclovir and other antivirals for suppression of HIV or hepatitis B/C virus are reached in plasma, synergistic or antagonistic effects on the activity of ganciclovir or other antivirals are hardly probable.

The potential for metabolic interaction of valacyclovir or famciclovir is low due to insignificant participation of cytochrome P450 in metabolism of valganciclovir and ganciclovir. Besides, ganciclovir is not a substrate for P-glycoprotein and has no effect on UDP-glucuronyl transferase (UGT enzyme). Therefore, metabolic interactions and interactions with valganciclovir or ganciclovir carrier proteins with the following classes of antivirals are considered unlikely:

• non-nucleoside reverse transcriptase inhibitors (NNRTIs), e.g., rilpivirine, etravirine, efavirenz;
• protease inhibitors (PI), for example, darunavir, boceprevir and telaprevir;
• entry inhibitors (fusion inhibitor and CCR5 coreceptor antagonist), e.g., enfuvirtide and maraviroc;
• HIV integrase chain transfer inhibitor, for example, raltegravir.

Since ganciclovir is excreted through the kidneys by glomerular filtration and active tubular secretion, the co-administration of valganciclovir and antiviral drugs which are also excreted by tubular secretion may lead to a change in valganciclovir blood plasma concentration and/or the co-administered medication. Some examples include nucleoside reverse transcriptase inhibitors (NRTIs) (including those used for the treatment of hepatitis B), for example, lamivudine, emtricitabine, tenofovir, adefovir and entecavir. Renal clearance of ganciclovir may be reduced due to neurotoxicity caused by such medications as cidofovir, foscarnet, NIOT (for example, tenofovir, adefovir). These medicinal products should only be considered for concomitant use with valganciclovir only if the potential benefits outweigh the potential risks (see Section Special warnings and precautions for use).

Other possible drug-to-drug interactions:
The toxic effect may be increased when taking valganciclovir together or immediately before or after taking other medications which suppress the reproduction of rapidly dividing marrow cell populations in the bone marrow, testicles and germ skin layers and gastrointestinal mucosa. Examples of such medications: dapsone, pentamidine, flucytosine, vincristine, vinblastine, adriamycin, amphotericin B, combinations of trimethoprim/sulfamides, nucleoside analogues, hydroxyurea and pegylated interferons /ribavirin (with or without boceprevir or telaprevir).

All these medicinal products should only be considered for concomitant use with valganciclovir only if the potential benefits outweigh the potential risks (see Section Special warnings and precautions for use).

Inform your doctor about all medications you are taking. Consult your doctor before you start taking any medication during treatment with Valganvir medicinal product.

Prior to the initiation of valganciclovir treatment, patients should be advised of the potential risks to the foetus. In animal studies, ganciclovir was found to be mutagenic, teratogenic, carcinogenic, and a suppressor of fertility. Valganciclovir should, therefore, be considered a potential teratogen and carcinogen in humans with the potential to cause birth defects and cancers. It is also considered likely that valganciclovir causes temporary or permanent inhibition of spermatogenesis. Women of child bearing potential must be advised to use effective contraception during treatment. During treatment with Valganvir medicinal product men must be advised to practice barrier contraception during treatment, and for at least 90 days thereafter (see Sections Administration during pregnancy and breast-feeding and Undesirable effects).

Valganciclovir has the potential to cause carcinogenicity and reproductive toxicity in the long term.

Severe leukopenia, neutropenia, anaemia, thrombocytopenia, pancytopenia, bone marrow failure and aplastic anaemia have been observed in patients treated with valganciclovir. Treatment should not be started if the absolute number of neutrophils is less than 500 cells/µl or the number of platelets is less than 25,000 cells/ml, as well as if hemoglobin level is below 80 g/l (see Sections Dosage and administration and Undesirable effects).

When extending prophylaxis beyond 100 days the possible risk of developing leukopenia and neutropenia should be taken into account.

Valganvir should be used with caution in patients with pre-existing haematological cytopenia or a history of drug-related haematological cytopenia and in patients receiving radiotherapy.

It is recommended that complete blood counts and platelet counts should be monitored regularly during therapy. Increased haematological monitoring may be warranted in patients with renal impairment and paediatrics, at a minimum each time the patient attends the transplant clinic. In patients developing severe leukopenia, neutropenia, anaemia and/or thrombocytopenia, it is recommended that treatment with haematopoietic growth factors and/or dose interruption be considered (see Section Dosage and administration).

The bioavailability of ganciclovir after a single dose of 900 mg valganciclovir is approximately 60%, compared with approximately 6% after administration of 1000 mg oral ganciclovir (as capsules). Ganciclovir overdose may be associated with life-threatening adverse reactions. Therefore, careful adherence to the dose recommendations is advised when instituting therapy, when switching from induction to maintenance therapy and in patients who may switch from oral ganciclovir to valganciclovir as Valganvir cannot be substituted for ganciclovir capsules on a one-to-one basis. Patients switching from ganciclovir capsules should be advised of the risk of overdosage if they take more than the prescribed number of Valganvir tablets (see Sections Dosage and administration and Overdose).

In patients with impaired renal function, dosage adjustments based on creatinine clearance are required (see Sections Dosage and administration and Pharmacokinetics).

For patients on dialysis (creatinine clearance < 10 ml/min), it is impossible to give recommendations on dosage, therefore Valganvir is not recommended for use in these patients (see Sections Dosage and administration and Pharmacokinetics).

Seizures have been reported in patients taking imipenem-cilastatin and ganciclovir. Valganvir should not be used concomitantly with imipenem-cilastatin unless the potential benefits outweigh the potential risks (see Section Interaction with other medicinal products).

Patients treated with valganciclovir and didanosine, medications that are known to be myelosuppressive (e.g., zidovudine), or substances affecting renal function, should be closely monitored for signs of added toxicity (see Section Interaction with other medicinal products).

The controlled clinical study using valganciclovir for the prophylactic treatment of CMV disease in transplantation did not include lung and intestinal transplant patients. Therefore, experience in these transplant patients is limited.

If you have one of the diseases or conditions listed above, be sure to consult your doctor before taking the medicinal product.

Contraception in males and females
Women of child bearing potential must be advised to use effective contraception. Male patients must be advised to practice barrier contraception during and for at least 90 days following treatment with Valganvir unless it is certain that the female partner is not at risk of pregnancy.

Pregnancy
The safety of valganciclovir for use in pregnant women has not been established. Its active metabolite, ganciclovir, readily diffuses across the human placenta. Based on its pharmacological mechanism of action and reproductive toxicity observed in animal studies with ganciclovir there is a risk of teratogenicity in humans.

Valganvir should not be used in pregnancy unless the therapeutic benefit for the mother outweighs the potential risk of teratogenic damage to the foetus.

Breast-feeding
It is unknown if ganciclovir is excreted in human breast milk, but the possibility of ganciclovir being excreted in the breast milk and causing serious adverse reactions in the nursing infant cannot be discounted. Therefore, breast-feeding must be discontinued.

No studies on the effects on ability to drive and use potentially dangerous machines have been performed.

Adverse reactions such as seizures, dizziness, ataxia and/or confusion have been reported with the use of valganciclovir and ganciclovir. If they occur, such effects may affect tasks requiring alertness, including the patient’s ability to drive and operate machinery.

Film-coated tablets 450 mg.
7 tablets in a blister made of blister foil (oriented polyamide / aluminum/PVC) and flexible packing based on aluminum foil. 3 blisters with guidelines for medical use in a carton.

Protect from light and moisture, at a temperature not above 25°C. Keep away from children.

2 years. Do not use after the expiration date.

State enterprise ACADEMPHARM
220141, 5/3 Kuprevicha Street, Minsk, Belarus,
Phone / Fax +375 17 268-63-64
production@academpharm.by
To report adverse reactions use the electronic application form on the manufacturer’s website: https://academpharm.by/en