万赛维的说明书

instruction manual

English name: Valganciclovir Hydrochloride Tablets

Product name: Wansaiwei

Generic name: Valganciclovir hydrochloride tablets

Indications:

It is suitable for the treatment of patients with acquired immunodeficiency syndrome (AIDS) combined with cytomegalovirus (CMV) retinitis and the prevention of CMV infection in high-risk solid organ transplant patients.

Usage and dosage:

1. Standard dose valganciclovir hydrochloride tablets for oral administration 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. Therefore, the dosage and usage instructions of Valganciclovir Hydrochloride Tablets described below should be strictly followed.

2. Induction treatment of CMV retinitis in adult patients. The recommended dose for patients with active CMV retinitis is 900 mg (two 450 mg tablets) taken twice a day for 21 days. Prolonged induction therapy may increase the risk of bone marrow toxicity.

3. For maintenance treatment of CMV retinitis, the recommended dose after induction therapy or for patients with inactive CMV retinitis is 900 mg (two 4.0 mg tablets) once daily. Induction therapy may be repeated in patients with worsening retinitis.

4. Prevention of CMV infection in transplant patients. The recommended dose for kidney transplant patients is 900 mg (two 4.0 mg tablets) once a day starting within 10 days after transplantation until 200 days after transplantation. The recommended dose for patients who have received a solid organ transplant other than a kidney is 900 mg (two 450 mg tablets) once daily starting within 10 days after transplantation and until 100 days after transplantation.

5. Special dosage guidelines: Patients with renal insufficiency should closely monitor serum creatinine or creatinine clearance levels. For adult patients, dosage should be adjusted based on creatinine clearance as shown in the table below.

Tablet dosage for patients with renal insufficiency: a. CrCl (ml/min) ≥ 60 induction dose 900 mg maintenance dose/preventive dose 2 times a day 900 mg once a day.

b.CrCl (ml/min) 40-59 induction dose 450 mg maintenance dose/preventive dose 2 times a day 450 mg once a day.

c.CrCl (ml/min) 25-39 induction dose 450 mg maintenance dose/prevention dose once a day 4.0 mg once every 2 days.

d.CrCl (ml/min) 10-24 induction dose 450 mg maintenance dose/preventive dose once every 2 days 450 mg twice a week.

Adverse reactions of Vancevi:

(1) Gastrointestinal system disorders: abdominal distension, cholangitis, indigestion, dysphagia, hiccups, esophagitis, fecal incontinence, flatulence, gastritis, gastrointestinal dysfunction, gastrointestinal bleeding, oral ulcers, pancreatitis, tongue dysfunction. (2) Systemic: ascites, weakness, bacterial, fungal and viral infections, bleeding, malaise, mucosal disease, pain, photosensitivity, chills, sepsis. (3) Liver dysfunction: hepatitis, jaundice. (4) Skin and appendages: acne, alopecia, seborrheic dermatitis, dry skin, increased sweating, urticaria. (5) Central and peripheral nervous system: abnormal dreaming, amnesia, anxiety, ataxia, coma, dry mouth, emotional instability, hyperkinesia syndrome, hypertonia, loss of libido, myoclonus, nervousness, drowsiness, abnormal thinking, and tremor. (6) Musculoskeletal system: musculoskeletal pain, myasthenic syndrome. (7) Urinary system: hematuria, impotence, renal failure, frequent urination. (8) Metabolism and nutrition: increased blood alkaline phosphatase, increased blood creatine phosphokinase, decreased blood sugar, increased blood lactate dehydrogenase, decreased blood magnesium, diabetes, edema, abnormal liver function, hypocalcemia, hypokalemia, hypoalbuminemia. (9) Special senses: amblyopia, blindness, earache, eye bleeding, eye pain, deafness, glaucoma, taste disorder, tinnitus, visual abnormalities, vitreous abnormalities. (10) Blood and lymphatic system: eosinophilia, leukocytosis, lymphadenopathy, splenomegaly. (11) Cardiovascular system: arrhythmia (including ventricular arrhythmia), deep thrombophlebitis, hypertension, hypotension, migraine, phlebitis, tachycardia, vasodilation. (12) Respiratory system: pleural effusion, sinus congestion. 7. Adverse events reported spontaneously after the marketing of intravenous and oral ganciclovir are not mentioned in the above sections. The following are adverse events that cannot be excluded and may be related to ganciclovir. Because valganciclovir hydrochloride tablets are rapidly and largely converted to ganciclovir, these adverse events may also occur while taking valganciclovir hydrochloride tablets. (1) Allergic reaction. (2) Decreased male fertility. (3) Adverse events reported after marketing are consistent with those observed in clinical trials of valganciclovir hydrochloride tablets and ganciclovir.

Notes on Wansaiwei:

The absolute bioavailability of valganciclovir hydrochloride tablets measured with ganciclovir is 10 times higher than that of ganciclovir capsules. Valganciclovir hydrochloride tablets cannot replace ganciclovir capsules in a 1:1 ratio. Patients who previously used ganciclovir capsules and want to switch to valganciclovir hydrochloride tablets should be informed that there is a risk of overdose if they take more than the prescribed dose of valganciclovir hydrochloride tablets.

Monitoring of complete blood count and platelet count is recommended during treatment. For patients with severe leukopenia, neutropenia, anemia and/or thrombocytopenia, it is recommended to use blood cell growth factor therapy and/or consider suspending medication.

For patients with renal insufficiency, the dose needs to be adjusted based on creatinine clearance.

For patients who have undergone hemodialysis (CrCl<10mL/min), no recommended dosage can be given. Therefore, Valganciclovir Hydrochloride Tablets cannot be used in such patients.

Convulsions, sedation, dizziness, ataxia, and/or confusion have been reported after administration of valganciclovir hydrochloride tablets and/or cyclovir. If these conditions occur, they may affect activities that require concentration, including the patient's ability to drive a car and operate machinery.

Convulsions have been reported in patients receiving imipenem-cilastatin (Tylon) and ganciclovir concomitantly. Valganciclovir hydrochloride tablets should not be used concomitantly with Tylenol unless the possible benefits outweigh the potential risks.

Zidovudine and valganciclovir hydrochloride tablets may cause neutropenia and anemia when used alone. Some patients may not tolerate the full dose of these two drugs.

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

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

Pregnant and lactating women should use Vancevir:

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.

Drug interactions:

Drug Interactions with Valganciclovir Hydrochloride Tablets: Studies in an in situ rat small intestinal permeability model showed that valganciclovir did not interact with valacyclovir, didanosin, nelfinavir, cyclosporine, omeprazole, and mycophenolate mofetil.

Valganciclovir hydrochloride tablets are metabolized into ganciclovir, so interactions with ganciclovir are expected to occur.

Drug interactions with ganciclovir: The plasma protein binding rate of ganciclovir is only 1-2%, so there will be no interaction competing for protein binding sites.

Imipenem-cilastatin (Taineng): Convulsions have been reported when ganciclovir and imipenem-cilastatin were combined. These two drugs should not be used together unless the possible benefits outweigh the potential risks.

Probenecid: Coadministration of probenecid with oral ganciclovir resulted in a statistically significant decrease (20%) in renal clearance of ganciclovir and a statistically significant increase (40%) in drug exposure. The mechanism of action for these changes is competitive tubular secretion. Therefore, patients taking valganciclovir hydrochloride tablets and probenecid together should be closely monitored for ganciclovir toxicity.

Zidovudine: When patients taking oral ganciclovir were combined with zidovudine, the area under the drug-time curve (AUC) of zidovudine increased slightly (17%), but it was statistically significant. Moreover, the combined use of the two drugs tended to decrease the blood concentration of ganciclovir, although there was no statistically significant difference. However, since both zidovudine and ganciclovir may cause neutropenia and anemia, some patients may not be able to tolerate full doses of both drugs.

Didanosine: Increased plasma concentrations of didanosine have been seen when coadministered with ganciclovir (either intravenously or orally). The area under the didanosine curve (AUC) of didanosine increased by 84-124% at oral doses of 3 and 6 g/day of ganciclovir; similarly, the AUC of didanosine increased by 38-67% at intravenous doses of 5 and 10 mg/kg/day. This increase cannot be explained by competitive tubular secretion because the percentage of didanosine secreted was also increased. This increase may be due to increased bioavailability or due to decreased metabolism. The effect on the plasma concentration of ganciclovir has no clinical significance. However, because didanosine plasma concentrations increase when the two drugs are used together, patients should be closely monitored for didanosine toxicity.

Mycophenolate mofetil: Based on the results of studies with single recommended oral doses of mycophenolate mofetil (MMF) and intravenous ganciclovir, as well as the known effects of renal insufficiency on the pharmacokinetics of MMF and ganciclovir, it is hypothesized that coadministration of these two drugs (which may compete for renal tubular secretion) will result in increased concentrations of mycophenolic acid glucuronide (MPAG) and ganciclovir. It is speculated that the pharmacokinetics of mycophenolic acid (MPA) are not significantly altered and therefore the dose of MMF does not need to be adjusted. If MMF and ganciclovir are coadministered in patients with renal insufficiency, the recommended dose of ganciclovir should be observed and the patient closely monitored.

Zalcitabine: Zalcitabine increases the area under the curve AUC0-8 of oral ganciclovir by 13%, and there is no statistically significant change in other pharmacokinetic parameters. In addition, although the clearance rate constant of zalcitabine was slightly increased when oral ganciclovir was coadministered, there were no clinically relevant changes in the pharmacokinetic characteristics.

Stavudine: No statistically significant interactions in pharmacokinetic parameters were observed when stavudine was coadministered with oral ganciclovir.

Trimethoprim: Trimethoprim reduces the renal clearance of oral ganciclovir by 16.3%, which is statistically significant, and correspondingly significantly reduces the terminal clearance and prolongs the half-life by 15%. However, these changes may not be clinically meaningful as AUC0-8 and Cmax are not affected. When trimethoprim was coadministered with ganciclovir, the only statistically significant change in the pharmacokinetic parameter of trimethoprim was a 12% increase in the trough concentration Cmin. However, this change may not be clinically significant and no dose adjustment is necessary.

Cyclosporin: There is no evidence that the use of ganciclovir affects the pharmacokinetic parameters of cyclosporin by comparing trough concentrations of cyclosporine. However, there is evidence that maximum serum creatinine values ​​increase after initiation of ganciclovir therapy.

Other Possible Drug Interactions: Toxicity may be increased when ganciclovir is coadministered with other drugs known to have myelosuppressive effects or drugs associated with renal insufficiency (e.g., dapsone, pentamidine, flucytosine, vincristine, vinblastine, doxorubicin, amphotericin B, nucleoside analogs, and hydroxyurea). Therefore, coadministration of ganciclovir with these drugs should only be considered if the benefits outweigh the risks.

Storage:

Should be stored at 30℃. Medicines should be stored out of the reach of children.