盐酸缬更昔洛韦片说明书

Instructions

Generic name: Valganciclovir (valganciclovir hydrochloride tablets)

Product name: valcyte

Full names: Valcyte, Valganciclovir hydrochloride tablets, valcyte, Valganciclovir, valgansiklovir

【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】

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 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.

【Notes】

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 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.

【Adverse reactions】

1. Experience in using Valganciclovir Hydrochloride Tablets: Valganciclovir is the prodrug of ganciclovir and is rapidly converted into ganciclovir after oral administration. Therefore, known adverse reactions associated with ganciclovir are expected to occur with the use of valganciclovir hydrochloride tablets. All adverse events observed in clinical studies of valganciclovir hydrochloride tablets have also been observed with ganciclovir. Adult patients:

(1) Treatment of CMV retinitis in AIDS patients:

In a clinical trial in which 79 patients in each group were randomly treated with valganciclovir or intravenous ganciclovir for 28 days (21 days of induction treatment and 7 days of maintenance treatment), the safety data of the two groups were comparable. The most frequently reported adverse events were diarrhea, neutropenia, and pyrexia. Diarrhea, oral candida infection, headache, and fatigue were more commonly reported in the oral valganciclovir group, whereas nausea and injection site-related events were more commonly reported in the intravenous ganciclovir group.

In both clinical trials (n=370), regardless of severity and whether drug-related, the most frequently reported adverse events (% of patients) in the valganciclovir hydrochloride treatment group were diarrhea (38%), pyrexia (26%), nausea (25%), neutropenia (24%), and anemia (22%). Most adverse events were mild or moderate. Regardless of severity, the most commonly reported events related to valganciclovir hydrochloride (including possibly unrelated, possibly related, and probably related) were neutropenia (21%), anemia (14%), diarrhea (13%), and nausea (9%).

(2) Prevention of CMV infection in organ transplant patients:

The adverse reaction data of Valganciclovir Hydrochloride Tablets come from a clinical trial. Solid organ transplant patients received valganciclovir (n=244) or oral ganciclovir (n=126), starting within 10 days after transplantation, until 100 days after transplantation, and observed until 28 days after drug withdrawal. Regardless of severity and whether drug-related, the most frequently reported adverse events (% of patients) in the valganciclovir treatment group (n=244) in this clinical trial were diarrhea (30%), tremor (28%), and graft rejection (24%), nausea (23%), headache (22%), leg edema (21%), constipation (20%), back pain (20%), insomnia (20%), hypertension (18%), and vomiting (16%). These adverse events were also seen in patients taking oral ganciclovir with similar rates. Most adverse events were mild to moderate.

Adverse events that occurred in clinical trials of solid organ transplantation (100-day dosing regimen) but not in clinical trials of CMV retinitis with an incidence of ≥2% included hypertension (18%), increased serum creatinine (10%) and metabolic disorders (hyperkalemia) (14%), and liver function abnormalities (9%). The incidence of these adverse events is similar to oral ganciclovir and may be considered to reflect the manifestations of the underlying disease.

The most commonly reported events, regardless of severity, related to this product (including possibly unrelated, possibly related, and probably related) were leukopenia (9%), diarrhea (7%), nausea (6%), and neutropenia (5%) in solid organ transplant patients treated up to 100 days after transplantation and in kidney transplant patients treated up to 200 days after transplantation: leukopenia, neutropenia, anemia, and diarrhea.

In high-risk renal transplant patients, the overall safety profile of the drug did not change as the prophylaxis cycle increased to 200 days. The reported incidence of leukopenia increased slightly over the 200-day period, whereas the incidence of neutropenia, anemia, and thrombocytopenia was the same in both groups.

2. Experience in using ganciclovir:

(1) Gastrointestinal system: abdominal distension, cholangitis, indigestion, dysphagia, belching, esophagitis, fecal incontinence, flatulence, gastritis, gastrointestinal dysfunction, gastrointestinal bleeding, oral ulcers, pancreatitis, tongue dysfunction.

(2) Systemic diseases: ascites, weakness, bacterial, fungal and viral infections, bleeding, fatigue, mucosal diseases, pain, photosensitivity, chills, sepsis.

(3) Liver function: hepatitis, jaundice.

(4) Skin and appendages: hair loss, dry skin, increased sweating, and urticaria.

(5) Central and peripheral nervous system: abnormal dreaming, amnesia, anxiety, ataxia, coma, dry mouth, affective disorders, hyperkinesia syndrome, hypertonia, loss of libido, myoclonus, tension, drowsiness, and abnormal thinking.

(6) Musculoskeletal system: musculoskeletal pain and 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, diabetes, and hypoalbuminemia.

(9) Special senses: amblyopia, blindness, earache, eye bleeding, eye pain, deafness, glaucoma, taste disorder, tinnitus, visual abnormalities, and vitreous abnormalities.

(10) Blood and lymphatic system: eosinophilia, leukocytosis, lymphadenopathy, and spleen enlargement.

(11) Cardiovascular system: arrhythmia (including ventricular arrhythmia), migraine, phlebitis, tachycardia, deep thrombophlebitis, vasodilation.

(12) Respiratory system: sinus congestion.

3. Post-launch experience:

Experience with Ganciclovir and Valganciclovir: Because valganciclovir hydrochloride is rapidly and extensively converted to ganciclovir, all ganciclovir-related adverse events may also occur while taking valganciclovir hydrochloride. Adverse events that have been 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 as possible related to ganciclovir: Anaphylaxis; Decreased male fertility. Post-marketing reported adverse events are consistent with those observed in clinical trials of valganciclovir hydrochloride tablets and ganciclovir.

【Taboo】

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.

【Storage method】

1. This product should be stored at 30℃.

2. Medicines should be stored out of reach of children.

[Validity period] 36 months