万赛维说明书

Instructions

Product name: Wansaiwei

Generic name: Valganciclovir hydrochloride tablets

English name: Valganciclovir Hydrochloride Tablets

[Ingredients of Vansavit]

The main ingredient of this product is valganciclovir hydrochloride, the chemical name is: 1L-valine-2[(2-amino-1,6-dihydro-6-oxy-9H-purin-9-yl)methoxy]-3-hydroxy-propyl ester monohydrochloride

Molecular formula: C12H22N6O5·HCl

Molecular weight: 390.83

[Indications of Vancevit]

Valganciclovir hydrochloride tablets are indicated for the treatment of cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS).

Valganciclovir hydrochloride tablets are suitable for preventing CMV infection in high-risk solid organ transplant patients.

[Usage and dosage of VANSAVI]

Note: The basic requirement to avoid overdose is to strictly follow the recommended dosage.

Standard dosage: Valganciclovir hydrochloride tablets are administered orally and should be taken with food. Valganciclovir hydrochloride tablets can be rapidly converted into ganciclovir in large quantities. The bioavailability of valganciclovir hydrochloride tablets as measured by ganciclovir is 10 times higher than that of ganciclovir capsules, so the dosage and usage instructions of valganciclovir hydrochloride tablets described below should be strictly followed.

Induction therapy of CMV retinitis: For patients with active CMV retinitis, the recommended dose is 900 mg (two 450 mg tablets) twice daily for 21 days. Prolonged induction therapy may increase the risk of bone marrow toxicity.

Maintenance treatment of CMV retinitis: After induction therapy, or in patients with inactive CMV retinitis, the recommended dose is 900 mg (two 450 mg tablets) once daily. Induction therapy may be repeated in patients with worsening retinitis.

Prevention of CMV infection in transplant patients: For patients who have received solid organ transplants, the recommended dose is 900 mg (two 450 mg tablets) once daily, starting within 10 days after transplantation and continuing until 100 days after transplantation.

Specific Dosage Guidelines

Patients with renal insufficiency: Serum creatinine or creatinine clearance levels should be monitored closely. Dosage adjustments should be made based on creatinine clearance as shown below.

For CrCl ≥ (greater than or equal to) 60mL/min, the induction dose is 900mg, twice a day; the maintenance dose is 900mg, once a day.

For CrCl 40-59mL/min, the induction dose is 450mg, twice a day; the maintenance dose is 450mg, once a day.

If the CrCl is 25-39mL/min, the induction dose is 900mg, once a day; the maintenance dose is 900mg, once every other day.

For CrCl 10-24mL/min, the induction dose is 900mg, once every other day; the maintenance dose is 900mg, twice a week.

The creatinine clearance rate can be estimated based on serum creatinine according to the following formula:

Male = [140-age (years) x weight (kg) ÷ (72) x [0.011 x serum creatinine (umol/L)].

Female = 0.85 × male value.

Patients undergoing hemodialysis: For patients undergoing hemodialysis (CrCl<10mL/min), no recommended dosage can be given, so valganciclovir hydrochloride tablets cannot be used for such patients.

Patients with severe leukopenia, neutropenia, anemia, thrombocytopenia and pancytopenia: Patients treated with valganciclovir hydrochloride tablets (or cyclovir) have cases of severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, bone marrow suppression and aplastic anemia. Do not start treatment with Valganciclovir Hydrochloride Tablets if the absolute neutrophil count is less than 500/uL, the platelet count is less than 25,000/uL, or the hemoglobin is less than 8 g/dl.

[Adverse reactions of Vancevir]

Gastrointestinal disorders: bloating, cholangitis, dyspepsia, dysphagia, hiccups, esophagitis, fecal incontinence, flatulence, gastritis, gastrointestinal disorders, gastrointestinal bleeding, oral ulcers, pancreatitis, tongue disorders

Systemic: ascites, asthenia, bacterial, fungal and viral infections, bleeding, malaise, mucosal disease, pain, photosensitivity, chills, sepsis.

Liver disorders: hepatitis, jaundice

Skin and appendages: Acne, alopecia, seborrheic dermatitis, dry skin, increased sweating, urticaria

Central and peripheral nervous system: abnormal dreaming, amnesia, anxiety, ataxia, coma, dry mouth, emotional instability, hyperkinesia syndrome, hypertonia, hyposexuality, myoclonus, nervousness, drowsiness, abnormal thinking, tremor

Musculo-skeletal system: musculoskeletal pain, myasthenic syndromes

Urinary system: hematuria, impotence, renal failure, frequent urination

Metabolism and Nutrition: Increased blood alkaline phosphatase, increased blood creatine phosphokinase, decreased blood glucose, increased blood lactate dehydrogenase, decreased blood magnesium, diabetes, edema, abnormal liver function, hypocalcemia, hypokalemia, hypoalbuminemia

Special senses: amblyopia, blindness, earache, eye bleeding, eye pain, deafness, glaucoma, taste disorder, tinnitus, visual abnormalities, vitreous abnormalities

Blood and lymphatic system: eosinophilia, leukocytosis, lymphadenopathy, splenomegaly

Cardiovascular system: cardiac arrhythmias (including ventricular arrhythmias), deep thrombophlebitis, hypertension, hypotension, migraine, phlebitis, tachycardia, vasodilation.

Respiratory system: pleural effusion, sinus congestion

[Taboo of Wansaiwei]

Valganciclovir Hydrochloride Tablets should not be used in patients with a known allergic reaction to valganciclovir, ganciclovir, or any other ingredient in the medicine. Due to the similar chemical structures of valganciclovir hydrochloride tablets to aciclovir and valaciclovir, there may be cross-allergic reactions between these drugs.

[Wansaiwei Warning]

Ganciclovir has been found to be mutagenic, teratogenic, deficient in spermatogenesis and carcinogenic in animal experiments. Therefore, valganciclovir hydrochloride tablets are also considered to have potential teratogenic and carcinogenic effects in the human body, and may cause birth defects and cancer. Valganciclovir hydrochloride tablets are also thought to cause temporary or permanent suppression of spermatogenesis.

[Notes on Wansaiwei]

Cross-allergic reaction

Because ganciclovir has a similar chemical structure to acyclovir and penciclovir, cross-allergic reactions may exist between these drugs. Therefore, valganciclovir hydrochloride tablets should be administered with caution to persons with known hypersensitivity to acyclovir or penciclovir (or to the prodrugs of these drugs, valacyclovir or famciclovir).

Mutagenicity, teratogenicity, carcinogenesis, fertility and contraception

In animal experiments, ganciclovir has been found to be mutagenic, teratogenic, carcinogenic and impair fertility. Therefore, it is believed that valganciclovir hydrochloride tablets have potential teratogenic and carcinogenic effects on the human body and may cause birth defects and cancer. Before initiating treatment with valganciclovir, patients should be warned of the potential risk to the fetus so that appropriate contraceptive measures can be used.

Based on clinical and nonclinical studies, valganciclovir hydrochloride tablets are also thought to cause temporary or permanent suppression of spermatogenesis.

Myelosuppression

Valganciclovir hydrochloride tablets should be used with caution in patients with a history of cytopenias or drug-related cytopenias and in patients undergoing radiation therapy.

Cases of severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, bone marrow failure, and aplastic anemia have been observed in patients treated with valganciclovir hydrochloride tablets (and ganciclovir). Treatment with valganciclovir hydrochloride tablets should not be started if the absolute neutrophil count is less than 500/μl, the platelet count is less than 25,000/μl, or the hemoglobin is less than 8 g/dl.

Monitoring of complete blood count and platelet count is recommended for all patients during treatment. In patients with severe leukopenia, neutropenia, anemia, and/or thrombocytopenia, treatment with blood cell growth factors is recommended and/or treatment withholding may be considered.

Concomitant use with other drugs Convulsive seizures have been reported in patients receiving imipenem-cilastatin and ganciclovir concomitantly. Valganciclovir hydrochloride tablets should not be used concomitantly with imipenem-cilastatin unless the possible benefits outweigh the potential risks.

Both zidovudine and valganciclovir hydrochloride tablets may cause neutropenia and anemia. Some patients may not tolerate the combined use of full doses of both drugs.

Plasma concentrations of didanosine may be increased when coadministered with valganciclovir hydrochloride tablets; therefore, patients should be closely monitored for didanosine toxicity.

Concomitant use of valganciclovir hydrochloride with other drugs known to be myelosuppressive or associated with impaired renal function may result in increased toxicity.

The bioavailability of valganciclovir hydrochloride tablets, measured as ganciclovir, is 10 times higher than that of ganciclovir capsules. Valganciclovir hydrochloride tablets cannot replace ganciclovir capsules at a ratio of 1:1. Patients who have been taking ganciclovir capsules and are switching to valganciclovir hydrochloride tablets should be informed of the risk of overdose if they take more than the prescribed dose of valganciclovir hydrochloride tablets.

Drug Abuse and Drug Dependence

There is no information on drug abuse and dependence for Valganciclovir Hydrochloride Tablets.

Effects on ability to drive and operate machinery

Adverse reactions such as convulsions, dizziness, and confusion have been reported after the use of valganciclovir hydrochloride tablets and/or cyclovir. If these conditions occur, they may affect activities that require alertness, including the patient's ability to drive a car and operate machinery.

Medication for special populations

Fertile men and women

fertility

In animal studies, ganciclovir has been found to impair fertility. In clinical studies, kidney transplant patients received valganciclovir hydrochloride tablets to prevent CMV infection for 200 days and were compared with untreated controls. Spermatogenesis is inhibited during treatment with Valganciclovir Hydrochloride Tablets. At follow-up approximately 6 months after discontinuation of treatment, mean sperm density in treated patients was similar to that observed in untreated controls.

Among patients treated with valganciclovir hydrochloride tablets, all patients (n=7) who had normal sperm density at baseline and 8 of 13 patients with low sperm density had normal sperm density after discontinuation of treatment. In the control group, all patients (n=6) with normal sperm density at baseline and 2 of 4 patients with lower sperm density had normal sperm density at the end of follow-up. Contraception

It is recommended that women of childbearing potential use effective contraception during treatment and for at least 30 days after treatment. Sexually active male patients are advised to use condoms during treatment with valganciclovir hydrochloride and for at least 90 days after discontinuation of treatment, unless the female partner is not at risk for pregnancy.

Patients with impaired renal function

In patients with impaired renal function, dosage adjustments may be required based on creatinine clearance.

Patients with impaired liver function

The safety and effectiveness of Valganciclovir Hydrochloride Tablets have not been established in patients with impaired hepatic function.

Save and process

Tablets must not be broken or crushed. Considering that valganciclovir hydrochloride tablets have potential teratogenic and carcinogenic effects in humans, special caution should be used when handling damaged tablets. Avoid direct contact with skin or mucous membranes with broken or crushed tablets. In the event of contact, rinse skin thoroughly with soap and water and eyes with sterile water. If sterile water is not available, clean water can be used instead. This medicine should not be used after the expiry date (EXP) shown on the packaging.

Disposal of unused or expired medications

Releases of pharmaceuticals into the environment should be minimized. Medications should not be disposed of with wastewater and should not be thrown away with household waste.

[Use of Vancevi for pregnant and lactating women]

Due to the rapid and substantial conversion of valganciclovir to ganciclovir, reproductive toxicity studies have not been repeated. In animal experiments, ganciclovir caused reduced fertility and teratogenic effects. It is recommended that women of childbearing potential use effective contraceptive measures during treatment. Male patients are advised to use barrier contraception during treatment with valganciclovir hydrochloride tablets and for at least 90 days after discontinuation of treatment.

There are no safety data on valganciclovir hydrochloride tablets during human pregnancy. Pregnant women should avoid the use of valganciclovir hydrochloride tablets unless the benefits to the mother far outweigh the potential harm to the fetus.

The developmental effects of valganciclovir or cyclovir on perinatal and postnatal infants have not been studied, but it must be considered that ganciclovir may be excreted in breast milk and cause serious adverse reactions in infants. Therefore, when considering the possible benefits of valganciclovir hydrochloride tablets to nursing mothers, a decision should be made to discontinue medication or discontinue breastfeeding.

[Vasavi Children’s Medication]

Safety and efficacy studies have not been conducted in children. Because the pharmacokinetics of valganciclovir hydrochloride tablets have not been studied in children, its use in children is not recommended.

[Drug use of VANSAVY for elderly patients]

Safety and efficacy studies have not been conducted in older adults.

[Overdose of Vancevir]

Valganciclovir overdose experience: An adult with renal impairment developed fatal myelosuppression for several days after receiving a dose that was at least 10 times the recommended dose corresponding to the patient's degree of renal impairment (reduced creatinine clearance).

It is speculated that excessive amounts of valganciclovir may also lead to increased nephrotoxicity.

In patients with valganciclovir overdose, hemodialysis and hydration may help reduce plasma concentrations.

Experience with Intravenous Ganciclovir Overdose: Overdoses with intravenous ganciclovir have been reported both in clinical trials and in postmarketing use. No adverse events were reported in some of these cases. The vast majority of patients have one or more of the following adverse events:

Hematological toxicity: pancytopenia, myelosuppression, myeloid aplastic anemia, leukopenia, neutropenia, granulocytopenia.

Hepatotoxicity: hepatitis, abnormal liver function.

Renal toxicity: patients with existing renal insufficiency may experience worsening of hematuria, acute renal failure, and increased creatinine.

Gastrointestinal toxicity: abdominal pain, diarrhea, vomiting.

Neurotoxicity: widespread tremors, convulsions.

【Wansaiwei Storage】

Vancevit should be stored below 30℃.

Should be stored out of the reach of children.