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Chinese name: Cidofovir lipid
Trade name: Vistide
Chemical name: Cidofovir
Specification and dose: 375mg/5mL; injection
Cidofovir (Ci dofovir) injection, Cidofovir is indicated for CMV retinitis (cytomegalovirus retinitis) in AIDS patients. Cidofovir has a high degree of inhibitory activity against CMV and is also active against certain virus strains that are resistant to ganciclovir or foscarnet. It also has strong activity against herpes simplex virus (HSV), herpes zoster virus (VZV), human papilloma virus (HPV), etc.
Usage and dosage:
Adults: 1. Intravenous infusion: treatment of cytomegalovirus retinitis in HIV-infected patients: the recommended dose is 5 mg/kg, diluted with 100 ml of normal saline and infused for 1 hour. Treatment is once a week for two weeks (induction phase), followed by doses of 5 mg/kg every other week until retinitis resolves or treatment-related toxicity develops. 0.9% normal saline is instilled for 1 to 2 hours before each medication. If tolerated, 1L of normal saline is instilled for 1 to 3 hours during treatment. At the same time, 2 g of probenecid was taken orally 3 hours before cidofovir infusion, and then 1 g of probenecid was taken orally at the 2nd and 8th hour after cidofovir infusion.
2. Intravitreal administration: Treatment of cytomegalovirus retinitis in HIV-infected patients: A single dose of cidofovir 20 μg (approximately 0.1 ml) is administered intravitreally, and then a second dose of 20 μg is determined based on the progression of retinitis shown by fundus photography. At the same time, 2 g of probenecid was taken orally 3 hours before the intravitreal injection of cidofovir, and 1 g of probenecid was taken orally at the 2nd and 8th hours after the injection to reduce intraocular pressure, especially the impact of cidofovir on the ciliary epithelium.
3. Dosage in renal insufficiency: If renal function changes during treatment, the dose should be reduced from 5 mg/kg to 3 mg/kg for every 0.3 to 1.4 mg/dl increase in serum creatinine. However, the medication should be stopped when serum creatinine is >1.5mg/dl.
Adverse reactions:
Toxic renal damage, neutropenia, peripheral neuropathy
Blood: Neutropenia, but neutropenia is not dose-related.
Central Nervous System: Peripheral neuropathy, fatigue, confusion, convulsions, abnormal gait, somnolence, and headache
In clinical trials: Anxiety has been reported, but causality has not been established.
Genitourinary system: Toxic renal damage has been reported during treatment, manifested by increased serum creatinine, proteinuria, glycosuria, and decreased plasma phosphate, uric acid, and bicarbonate. Fanconi syndrome and cidofovir-induced diabetes insipidus have also been reported.
Metabolic/endocrine system: Metabolic acidosis has been reported during treatment. There have also been reports of death from metabolic acidosis in patients with liver dysfunction and pancreatitis after taking the drug.
Gastrointestinal: Nausea (7%), vomiting (7%), and diarrhea (26%) have been reported during treatment.
Skin: Skin erosions and ulcers have been reported during treatment.
Eye: Iritis, changes in intraocular pressure, vision loss, and uveitis have been reported during treatment.
Ear: Ototoxicity (hearing loss with or without tinnitus) has been reported during treatment.
Allergic Reactions: Allergic reactions have been reported during treatment.
Contraindications:
1. People who are allergic to this medicine.
2. Those who are allergic to probenecid or sulfa drugs.
3. Patients with severe renal impairment (serum creatinine >1.5mg/dl, creatinine clearance ≤55ml/min, or urine protein concentration ≥100mg/dl).
Precautions:
Use with caution in patients with renal insufficiency.
Effects of Drugs on Children The safety and effectiveness of drugs in children are not yet clear.
Effects of the drug on pregnancy The U.S. Drug and Food Administration (FDA) has classified the pregnancy safety of this drug as level C.
Effects of the drug on lactation It is not clear whether this drug can be excreted in breast milk.
Before each treatment with this drug, a large dose of probenecid should be taken orally and normal saline should be infused intravenously (at least 1L of 0.9% sodium chloride) to reduce the incidence of toxic kidney damage. Patients should be monitored for serum creatinine and urine protein after infusion and dose adjusted accordingly.
Direct intraocular injection of this drug is prohibited.
If renal function changes occur during treatment, the dose should be reduced or discontinued.
Other potentially nephrotoxic drugs should be stopped 7 days before treatment with cidofovir.
Cidofovir alone does not affect the pharmacokinetics of zidovudine. However, probenecid, which is often used in combination with this drug during treatment, can inhibit the renal clearance of zidovudine. Increased zidovudine plasma concentrations and influenza-like symptoms (myalgia, malaise, fever), maculopapular rash, and hematological toxicity. Therefore, zidovudine should be discontinued or the dose reduced by half when taking cidofovir/probenecid in patients receiving zidovudine.
Storage:
Store container in refrigerator at 2°C to 8°C (36°F to 46°F).
Light-protected vials are kept in external cartons.
Do not freeze and shake vials vigorously.
Mechanism of action:
This drug is an acyclic nucleoside phosphate derivative with antiviral activity. Its mechanism of action is to competitively inhibit deoxycytosine-5-triphosphate, inhibit the viral DNA polymerase and incorporate into the viral DNA, causing it to lose stability, further slowing down the synthesis of DNA to eliminate the virus. In addition, because this drug is converted by cellular kinases into its active diphosphate form in the body without relying on viral infection, unlike ganciclovir, viruses are less likely to develop resistance to this drug.
Safety and efficacy:
100 AIDS patients with an average CD4+ count of 6/nanoliter and CMV retinitis patients who had relapsed or were unable to tolerate ganciclovir and foscarnet treatment were administered intravenously with two doses of this product for a randomized controlled trial. Patients were injected with 5 mg/kg once a week for two weeks, and then injected with 5 mg/kg (high-dose group) or 3 mg/kg (low-dose group) every other week, along with 4 grams of probenecid and two liters of normal saline. As assessed by retinal photography, both groups were able to delay the appearance of new lesions or prevent existing lesions from worsening, and there was a significant difference in the average time that the high dose delayed the development of the disease and the lower dose group.
In another group of trials, 48 patients with AIDS and untreated CMV retinitis were randomly divided into an immediate treatment group and a delayed treatment group. The average CD4+ count in the immediate treatment group was 6/nanol, and 5 mg/kg was injected intravenously once a week for two weeks, followed by injections of 5 mg/kg every other week; the average CD4+ count in the delayed treatment group was 9/nl. Once CMV retinitis developed, cidofovir was immediately treated, and both treatment groups were injected with 4 grams of probenecid and 1 liter of normal saline at the same time. The results were that the average time to develop CMV retinitis was 120 days in the immediate treatment group and 22 days in the delayed treatment group (P<0.001). In the delayed treatment group, the 16 patients who began to develop symptoms of CMV retinitis after an average of 19 days took an average of 169 days to develop CMV retinitis after treatment with cidofovir (P=0.002)