盐酸缬更昔洛韦片的说明书

Tablet instructions

Generic name: Valganciclovir hydrochloride tablets

English name: Valganciclovir Hydrochloride Tablets

Chinese Pinyin: Yansuan Jiegengxiluowei Pian

Indications: In May 2001, the US FDA approved the market. Valcyte hydrochloride tablets are clinically used to treat acute retinitis caused by CMV infection in patients with acquired immune deficiency syndrome. In May 2003, its indications were expanded. Valcyte hydrochloride tablets are used to prevent and treat secondary CMV infection in organ transplant recipients. On August 11, 2010, Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced that the U.S. Food and Drug Administration (FDA) approved valganciclovir hydrochloride tablets (Valcyte) for the treatment of adult kidney transplant patients at high risk for cytomegalovirus (CMV) disease.

Usage and 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 amounts. 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. Prophylaxis of CMV Infection in Transplant Patients: For patients who have received a solid organ transplant, 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. Special Dosage Guidelines in Patients with Renal Impairment: 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) 60 mL/min, the induction dose is 900 mg, twice a day; the maintenance dose is 900 mg, once a day. If the CrCl is 40-59 mL/min, the induction dose is 450 mg, twice a day; the maintenance dose is 450 mg, once a day. If the CrCl is 25-39 mL/min, the induction dose is 900 mg, once a day; the maintenance dose is 900 mg, once every other day. If the CrCl is 10-24 mL/min, the induction dose is 900 mg, once every other day; the maintenance dose is 900 mg, 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<10 mL/min), no recommended dose can be given, so valganciclovir hydrochloride tablets cannot be used in 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 initiate 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:

Gastrointestinal disorders: abdominal 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: Hair loss, 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 inosine phosphokinase, decreased blood sugar, increased blood lactate dehydrogenase, diabetes, 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), migraine, phlebitis, tachycardia, deep thrombophlebitis, vasodilation. Respiratory system: sinus congestion.

Things to note:

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), it is recommended to use ganciclovir intravenous preparation (instead of valganciclovir hydrochloride tablets) and calculate the dose according to the dose reduction formula on the approved ganciclovir prescription information.

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.

Medication for special populations:

Children: No safety and efficacy data are available in these patients. Valganciclovir hydrochloride tablets are not recommended for use in children because the pharmacokinetics of valganciclovir hydrochloride tablets in such patients have not been established.

Pregnancy and Lactation: Pregnancy Category C 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 teratogenicity. 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 the perinatal and postnatal infant have not been studied, but it must be considered that ganciclovir may be excreted in breast milk and cause serious adverse reactions in nursing infants. Therefore, when considering the possible benefits of valganciclovir hydrochloride tablets to nursing mothers, a decision should be made whether to interrupt medication or breast-feeding.

Elderly: No safety and efficacy data are available in these patients.

Pharmacological effects of tablets: Valganciclovir is the L-valyl ester (prodrug) of ganciclovir. After oral administration, it is rapidly converted into ganciclovir by esterases in the small intestine and liver. Ganciclovir is a synthetic 2'-deoxyguanosine analog that inhibits herpes virus replication in vitro and in vivo. Susceptible human viruses include human cytomegalovirus (HCMV), herpes simplex virus-1 and herpes simplex virus-2 (HSV-1, HSV-2), human herpesvirus-6, 7, 8 (HHV-6, 7, 8), Epstein-Barr virus, varicella-zoster virus (VZV), and hepatitis B virus. In cells infected with cytomegalovirus (CMV), ganciclovir is first phosphorylated by the viral protein kinase UL97 to ganciclovir monophosphate. It is further phosphorylated by intracellular protein kinases into ganciclovir triphosphate, which is then slowly metabolized within the cell. After removal of extracellular ganciclovir, the observed half-life of ganciclovir in HSV- or HCMV-infected cells was 18 hours (6-24 hours), respectively. Since the phosphorylation process relies heavily on viral protein kinases, ganciclovir phosphorylation occurs preferentially in virus-infected cells. Ganciclovir inhibits viral activity mainly by inhibiting the synthesis of viral DNA: (a) Competitively inhibits viral DNA polymerase, preventing deoxyguanosine triphosphate from binding to DNA; (b) Ganciclovir triphosphate binds to viral DNA to terminate or limit the elongation of the viral DNA chain. The IC50 of the antiviral effect of ganciclovir on CMV in vitro ranges from 0.08 mcM (0.02 ug/mL) to 14mcM (3.5 ug/mL).