Valganolek^® (Tablets) Instructions for Use

Marketing Authorization Holder

NANOLEK LLC (Russia)

ATC Code

J05AB14 (Valganciclovir)

Active Substance

Valganciclovir (Rec.INN registered by WHO)

Dosage Form

Valganolek®

Film-coated tablets, 450 mg: 30, 60, or 90 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white or almost white, oval, biconvex; white or almost white on the cross-section.

Excipients: microcrystalline cellulose – 53.75 mg, povidone (Kollidon K30) – 23.91 mg, crospovidone (Kollidon CL) – 17.94 mg, magnesium stearate – 5.98 mg.

Film coating composition: Opadry white 03F280030 (OPADRY^® 03F280030 White) – 17.9 mg (hypromellose – 65%, macrogol – 13%, talc – 2%, titanium dioxide – 20%) – 17.9 mg. Coated tablet mass – 615.8 mg.

30 pcs. – polyethylene jars with first-opening control (1) – cardboard packs.
60 pcs. – polyethylene jars with first-opening control (1) – cardboard packs.
90 pcs. – polyethylene jars with first-opening control (1) – cardboard packs.

Clinical-Pharmacological Group

Antiviral drug

Pharmacotherapeutic Group

Systemic antiviral agent; direct-acting antiviral agent; nucleosides and nucleotides, except reverse transcriptase inhibitors

Pharmacological Action

Antiviral agent, L-valyl ester of ganciclovir. It is a prodrug of ganciclovir. After oral administration, it is rapidly converted to ganciclovir by esterases in the intestine and liver.

Ganciclovir is a synthetic analogue of guanine. Inside the cell, ganciclovir is sequentially metabolized to the monophosphate form by cellular deoxyguanosine kinase, then to the active ganciclovir triphosphate. Acting as a substrate and being incorporated into DNA, ganciclovir triphosphate competitively inhibits viral DNA synthesis. This leads to suppression of DNA synthesis by inhibiting DNA chain elongation. Ganciclovir inhibits viral DNA polymerase more effectively than cellular polymerase.

Human cytomegalovirus, Herpes simplex types 1 and 2, Varicella zoster, Epstein-Barr virus, and hepatitis B virus are sensitive to valganciclovir.

Pharmacokinetics

After oral administration, it is rapidly absorbed from the gastrointestinal tract, converted to ganciclovir in the intestinal wall and liver. The absolute bioavailability of ganciclovir after its conversion from valganciclovir is approximately 60%. The binding of ganciclovir to plasma proteins is 1-2%.

It is mainly excreted by the kidneys.

After valganciclovir administration, the terminal T_1/2 of ganciclovir is about 4.2 hours.

Indications

Treatment of cytomegalovirus retinitis in AIDS.

Prevention of CMV infection after organ transplantation in at-risk patients.

ICD codes

Dosage Regimen

Take orally with food.

For treatment of cytomegalovirus retinitis in AIDS: The recommended dose is 900 mg taken twice daily for 21 days as induction therapy. For maintenance therapy, use 900 mg once daily.

For prevention of CMV disease in solid organ transplant recipients: The recommended dose is 900 mg once daily, starting within 10 days of transplantation and continuing until 100 days post-transplant.

Adjust the dosage for all patients based on renal function. Calculate the creatinine clearance (CrCl) using the Cockcroft-Gault formula.

For patients with CrCl ≥ 60 mL/min, use the standard dose of 900 mg twice daily (induction) or 900 mg once daily (maintenance/prevention).

For patients with CrCl 40-59 mL/min, use 450 mg twice daily (induction) or 450 mg once daily (maintenance/prevention).

For patients with CrCl 25-39 mL/min, use 450 mg once daily (induction) or 450 mg every two days (maintenance/prevention).

For patients with CrCl 10-24 mL/min, use 450 mg every two days (all indications).

Do not use for patients with CrCl < 10 mL/min or those on hemodialysis. For patients on hemodialysis, consider an alternative therapy; valganciclovir is not recommended.

Monitor complete blood count (CBC) with differential and platelet count frequently. Do not initiate therapy if the absolute neutrophil count is below 500 cells/µL, the platelet count is below 25,000/µL, or the hemoglobin is below 80 g/L.

For patients experiencing neutropenia, anemia, or thrombocytopenia, consider dose interruption, dose reduction, or use of hematopoietic growth factors.

Tablets must be swallowed whole; do not crush or break.

Adverse Reactions

Digestive system:diarrhea, nausea, vomiting, abdominal pain, constipation, upper abdominal pain, dyspepsia, flatulence, ascites, impaired liver function.

Hematopoietic system:neutropenia, anemia, thrombocytopenia, leukopenia; pancytopenia, bone marrow suppression, aplastic anemia; potentially life-threatening bleeding associated with thrombocytopenia.

Infectious complications:oral candidiasis, pharyngitis/nasopharyngitis, sinusitis, upper respiratory tract infections, influenza, pneumonia, bronchitis, pneumocystis pneumonia, urinary tract infections.

Nervous system:headache, insomnia, peripheral neuropathy, paresthesia, tremor, dizziness (excluding vertigo), depression, seizures, psychotic disorders, hallucinations, confusion, agitation.

Skin and subcutaneous tissue:dermatitis, night sweats, pruritus, acne.

Respiratory system:cough, dyspnea, productive cough, nasal discharge, pleural effusion.

Sensory organs:retinal detachment, blurred vision.

Musculoskeletal system:back pain, arthralgia, muscle cramps, limb pain.

Urinary system:renal failure, dysuria, decreased creatinine clearance.

Immune system:graft rejection reaction.

Metabolism:anorexia, cachexia, decreased appetite, dehydration, weight loss.

Cardiovascular system:arterial hypotension, arterial hypertension.

Laboratory parameters:hyperkalemia, hypokalemia, hypomagnesemia, hyperglycemia, hypophosphatemia, hypocalcemia, hypercreatininemia.

Postoperative complications:postoperative complications, postoperative pain, postoperative wound infection, increased need for drainage, poor postoperative wound healing.

General disorders:fever, fatigue, lower limb edema, pain, edema, peripheral edema, weakness, hypersensitivity reactions to valganciclovir.

Contraindications

Absolute neutrophil count <500/µL, platelet count <25,000/µL; hemoglobin level <80 g/L; creatinine clearance <10 mL/min; pregnancy, breastfeeding period; children under 12 years of age; hypersensitivity to valganciclovir, ganciclovir.

With caution

Renal failure, elderly patients (safety and efficacy not established).

Due to the similar chemical structure of valganciclovir, acyclovir, and valacyclovir, cross-sensitivity reactions to these substances are possible.

Use in Pregnancy and Lactation

Contraindicated during pregnancy and breastfeeding.

Use in Renal Impairment

Dosage adjustment is required for patients with impaired renal function and patients on hemodialysis.

Pediatric Use

Contraindicated in children under 12 years of age.

Geriatric Use

Use with caution in elderly patients.

Special Precautions

Due to the similar chemical structure of valganciclovir and acyclovir, valacyclovir, cross-sensitivity reactions to these drugs are possible.

Use with caution in elderly patients (safety and efficacy of the drug have not been established).

Experimental animal studies have revealed mutagenic, teratogenic, aspermatogenic, and carcinogenic effects of ganciclovir. Valganciclovir should be considered a potential human teratogen and carcinogen, the use of which may cause congenital malformations and cancer. Furthermore, it is likely that Valganciclovir may temporarily or irreversibly suppress spermatogenesis.

Treatment should not be initiated if the absolute neutrophil count is less than 500 cells/µL, or the platelet count is less than 25,000 cells/µL, or if hemoglobin is below 80 g/L.

During treatment, it is recommended to regularly monitor the complete blood count and platelets. Patients with severe leukopenia, neutropenia, anemia and/or thrombocytopenia are recommended to be prescribed hematopoietic growth factors and/or to discontinue valganciclovir.

Concomitant use of valganciclovir and imipenem/cilastatin should be avoided unless the potential benefits of treatment outweigh the possible risk.

Since both zidovudine and ganciclovir can cause neutropenia and anemia, some patients may experience intolerance when taking valganciclovir and zidovudine concurrently at full doses.

Due to the possible increase in plasma concentrations of didanosine in the presence of ganciclovir, patients should be carefully monitored for symptoms of didanosine toxicity.

Effect on ability to drive vehicles and operate machinery

During treatment with valganciclovir and/or ganciclovir, seizures, sedative effect, dizziness, ataxia, and/or confusion may occur, which may adversely affect activities requiring increased concentration, including driving vehicles and operating machinery.

Drug Interactions

Valganciclovir is converted to ganciclovir, therefore interactions characteristic of ganciclovir can be expected with the use of valganciclovir.

Concomitant use of valganciclovir with other drugs that have myelosuppressive or nephrotoxic effects may enhance their toxic effects.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.