What Factors Affect a Sufficient Valacyclovir Dose?

Valacyclovir hydrochloride tablets, this product is suitable for the treatment of shingles. This product is suitable for treating herpes simplex virus infection. This product is suitable for preventing (inhibiting) the recurrence of herpes simplex virus infection.

Drug Name: Valacyclovir hydrochloride tablets
Drug type: Occupational injury medical insurance

Hanyu Pinyin: Yan Suan Fa Xi Luo Wei Pian
Use classification: Reverse transcriptase inhibitor

Valacyclovir hydrochloride tablets ingredients

Chemical name: L-valine-2-[[6-oxo-2-amino-1,6-dihydro-9H-purine-9-yl) methoxy] ethyl ester hydrochloride.
Chemical Structure:

Molecular formula: C ₁₃ H ₂₀ N ₆ O ₄ · HCl
Molecular weight: 360.8

Characteristics of valacyclovir hydrochloride tablets

This product is a film-coated tablet. It appears white to off-white after removing the film coating.

Indications of valacyclovir hydrochloride

This product is suitable for the treatment of shingles.
This product is suitable for treating herpes simplex virus infection.
This product is suitable for preventing (inhibiting) the recurrence of herpes simplex virus infection.

Specifications of valacyclovir hydrochloride tablets

0.5 g (based on valacyclovir).

Dosage and dosage of valacyclovir hydrochloride tablets

Adults Herpes zoster treatment: 500 mg orally, 2 tablets 3 times a day for 7 days. Herpes simplex treatment: 500mg orally, twice daily. The first episode may be more severe, and the course of treatment needs to be extended to 10 days. For recurrent infections, the course of treatment should be 5 days. Treatment is recommended to begin during the pre-symptomatic phase or immediately after the onset of symptoms and signs.
Treatment (inhibition) of herpes simplex virus infection:
For patients with normal immune function, take 500 mg of this product orally once daily.
For patients with frequent relapses (10 times per year), a 250 mg twice daily dosing regimen is more effective.
For immunodeficiency patients, the dosage regimen is 500 mg twice daily.
Renal function impairment < br For patients with apparently impaired renal function, the dosage of this product should be adjusted as follows:
Renal function (creatinine dose adjustment clearance rate ml / min)
Shingles herpes simplex treatment to prevent immune function normal immune deficiency 15-30 1000mg twice daily without adjustment without adjustment <15 1000mg once daily 500mg once daily 250mg once daily 500mg once daily hemodialysis For patients, the dose of this product should be the recommended dose for patients with creatinine clearance <15ml / min, but it should be administered after the completion of hemodialysis.
Hepatic impairment < br Patients with mild to moderate liver cirrhosis (synthetic liver function can be maintained) do not need to adjust the dosage of this product.
The pharmacokinetic data of patients with advanced liver cirrhosis (impaired liver synthesis and portal vein shunt) suggest that no dose adjustment is necessary, but clinical experience in this area is limited.

Adverse reactions of valacyclovir hydrochloride tablets

Adverse reactions were classified according to MedDRA human organ classification and frequency of occurrence as follows.
The frequency classification criteria are:
Very common: (10%),
Common (1%, <10%),
Uncommon (0.1%, <1%),
Rare (0.01%, <0.1%),
Very rare (<0.01%).
The adverse reactions in clinical trial data were classified according to the above-mentioned frequency standard, and the experimental data proved that the adverse reactions were related to this product (ie, the incidence of adverse reactions in patients receiving this product and placebo was statistically significantly different). All other adverse event frequencies were allocated based on spontaneously reported post-market data.
Clinical trial data Common: headache.
Gastrointestinal Tract < br Common: Nausea.
Post-marketing data Blood and lymphatic system < br Very rare: Leukopenia, thrombocytopenia.
Leukopenia is mainly seen in patients with immunodeficiency.
Immune system < br Very rare: allergic reactions.
Mental and Nervous System Rarely: dizziness, confusion, hallucinations, loss of consciousness.
Very rare: excitement, tremor, ataxia, difficulty articulation, psychotic symptoms, convulsions, encephalopathy, coma.
The above adverse reactions are generally reversible and are usually seen in patients with impaired renal function or other inducing factors. The incidence of neurological reactions in organ transplant patients who received high-dose valacyclovir hydrochloride to prevent CMV was higher than in patients in the low-dose group.
Respiratory system < br Uncommon: difficulty breathing.
Gastrointestinal tract Rare : abdominal discomfort, vomiting, diarrhea.
Liver < br Very rare: liver function tests are reversible.
Occasionally hepatitis is described.
Skin and connective tissue Uncommon: Skin rashes include photosensitivity.
Rare: itching.
Very rare: rubella, angioedema.
Kidney and urinary system < br Rare: Impaired renal function.
Very rare: acute kidney failure, kidney pain.
Renal pain may be related to renal failure.
Others: In extended clinical trials, patients with severe immunosuppression, especially those with advanced HIV infection, who took large doses (8g daily) of valacyclovir, reported renal insufficiency, capillary hemolytic anemia, and thrombocytopenia (sometimes Both exist). The same applies to patients with the same underlying disease or comorbidities, but not treated with valacyclovir.

Contraindications of valacyclovir hydrochloride tablets

This product is contraindicated in patients who are allergic to valacyclovir, acyclovir or any component of this product.

Precautions for valacyclovir hydrochloride tablets

Body fluid status < br Special care should be taken to ensure that patients (especially elderly patients) consume sufficient amounts of water to prevent dehydration in patients.
Patients with renal impairment:
For patients with significant renal impairment, the dose of valacyclovir should be adjusted (see [Dosage and Administration]). Patients with a history of altered renal function are at higher risk for neurological adverse reactions (see [Adverse Reactions]).
No special attention is paid to the influence on driving and mechanical operation ability.

Valacyclovir hydrochloride tablets for pregnant and lactating women

Pregnancy < br There is limited information on the use of this product in pregnant patients. Women in pregnancy should only use it if the expected efficacy of the treatment significantly exceeds the risk.
Existing studies of pregnant women exposed to acyclovir (active metabolite of valacyclovir) have shown that the incidence of fetal birth defects does not increase compared with the incidence of fetal birth defects in the general population Defects have no special characteristics in common and cannot be explained by their common cause. However, given the limited records and data on the use of valacyclovir, no clear conclusions can be drawn regarding the safety and reliability of this product during pregnancy.
After using this product at 1000mg and 3000mg, the daily AUC is 2-4 times higher than the AUC that can be achieved by oral acyclovir 1000 mg / day.
Breastfeeding < br Avaliclovir is the main metabolite secreted by valvacyclovir in milk. The acyclovir concentration detected in milk is equivalent to 0.6-4.1 times the plasma concentration of acyclovir. It is estimated that 200 mg of acyclovir (Suweiler®) orally, 5 times a day, the average steady-state peak plasma concentration (Cmax) after administration is 3.1 M (0.7 g / ml). This is equivalent to exposing the infant to an acyclovir dose of approximately 0.3 mg / day. Acyclovir has been demonstrated to have a clearing half-life of 2.8 hours in milk, which is similar to plasma half-life. Therefore, caution should be exercised when using this product for women who breastfeed. However, the intravenous dose of acyclovir for the treatment of neonatal herpes simplex is 30 mg / kg / day.

Valaciclovir hydrochloride tablets for children

There are no data on treating pediatric patients.

Valaciclovir hydrochloride tablets for elderly

No dose adjustment is required unless the renal function is significantly impaired. Sufficient water should be maintained.

Valacyclovir hydrochloride tablets drug interactions

No significant drug interactions were found.
Cimetidine and probenecid can increase the AUC of acyclovir by reducing renal clearance, but no dose adjustment is needed due to the large acyclovir treatment index. Other drugs that affect kidney physiology may also affect acyclovir's plasma levels.

Valacyclovir hydrochloride tablets overdose

Information on overdose of this product is limited. However, some patients received acyclovir in a single dose of 20 g, and after absorption through the gastrointestinal tract, there was no common toxic reaction.
A few days after an accidental repeated oral overdose of acyclovir, gastrointestinal reactions (such as nausea, vomiting) and neurological reactions (headache and confusion) were observed associated with it.
Intravenous overdose of acyclovir can cause an increase in plasma creatinine, which can lead to renal failure. There are also neurological reactions associated with intravenous overuse of acyclovir, including confusion, hallucinations, excitement, convulsions, and coma.
Patients should be closely observed for symptoms of poisoning. Hemodialysis can significantly improve the clearance of acyclovir from the blood, so it can be used as an option for treatment after overdose.

Pharmacology and toxicology of valacyclovir hydrochloride tablets

Pharmacological effects < br Pharmacotherapy subgroups:
Valacyclovir is an antiviral agent and is the L-valine ester of acyclovir. Acyclovir is a purine (guanine) nucleoside analog.
In the human body, valacyclovir is almost completely converted into acyclovir and valine by the action of valacyclovir hydrolase.
Acyclovir is a specific inhibitor of herpes virus. It inhibits herpes simplex virus (HSV) type 1 and type 2, varicella zoster virus (VZV), cytomegalovirus (CMV), EB virus (EBV), and Effect of human herpes virus 6 (HHV-6). After acyclovir is phosphorylated and converted into an active triphosphate form, it can play a role in inhibiting viral DNA synthesis.
The first step of phosphorylation requires the activity of a virus-specific enzyme. For HSV, VZV, and EBV, the enzyme is viral thymidine kinase (TK), which is only found in virus-infected cells. This selectivity persists in phosphorylated CMV, at least partly mediated by the gene product of the UL97 phosphotransferase. Acyclovir activation requires a virus-specific enzyme, a condition that explains its selectivity for action.
The phosphorylation process is accomplished by the action of cell kinases (conversion from monophosphate to triphosphate). Aciclovir triphosphate competitively inhibits viral DNA polymerase, and binding to this nucleoside analog results in termination of the specialized chain, interrupting viral DNA synthesis, and thereby blocking viral replication.
In clinical trials for the treatment of shingles, this product can reduce the pain associated with shingles, including acute pain and postherpetic neuralgia, and it can also shorten the time to form new lesions.
Extensive clinical monitoring of patients receiving acyclovir treatment or prophylaxis has shown that decreased sensitivity to acyclovir is rare in patients with healthy immune function, occasionally in patients with severe immunodeficiency, such as solid organ or bone marrow transplant patients Patients with malignant tumors receiving chemotherapy and those infected with human immunodeficiency virus (HIV).
Drug resistance is generally caused by a thymine kinase-deficient phenotype, which puts the virus in a very disadvantaged position in the natural host. In rare cases, reduced sensitivity to acyclovir may be caused by mutations in the virus thymine kinase or DNA polymerase. The virulence of these variants is similar to that of wild-type virus strains.
Toxicity studies < br Mutagenicity: Mutagenicity test results in vivo and in vitro show that valacyclovir is not genetically dangerous to humans.
Carcinogenicity: Bioassays in rats and mice indicate that valacyclovir is not carcinogenic.
Teratogenicity: Valacyclovir has no teratogenic effect on rats and rabbits, and almost all is metabolized to acyclovir.
In internationally recognized experiments, subcutaneous injection of acyclovir in rats and rabbits did not cause teratogenic effects. In another rat study, abnormal fetal rats were found when subcutaneous plasma concentrations reached 100 g / ml, which caused poisoning in female rats.
Fertility: Oral administration of valacyclovir does not affect fertility in male and female rats.

Pharmacokinetics of valacyclovir hydrochloride tablets

General characteristics:
Valacyclovir is completely and rapidly absorbed orally and is almost completely converted into acyclovir and valine. This transformation process may be completed by the enzyme isolating valacyclovir hydrolase in human liver.
Acyclovir in 1000 mg valacyclovir is 54% bioavailable and is not affected by food. The bioavailability of acyclovir 500 mg valacyclovir twice daily was 2.6 times higher than that of valacyclovir 200 mg and acyclovir 5 mg daily.
After oral administration of valacyclovir 1000 mg 3 times a day, the daily AUC (area under the blood concentration-time curve) ratio of acyclovir to 800 mg of valacyclovir 5 times a day orally After the AUC value is 2 times higher.
After valacyclovir 500 mg was administered twice daily, Cmax and AUC of acyclovir were 4 times and 1.8 times higher than the predicted values of valacyclovir 200 mg administered 5 times daily, respectively.
After a single dose of 250-1000 mg of valacyclovir, the average peak concentration of acyclovir is 10-25 M (2.2-5.7 g / ml), and the average peak time is 1.5 hours after administration.
The peak plasma concentration of valacyclovir is only 4% of acyclovir, and the average peak time is 30-60 minutes after administration, and the blood concentration drops below detectable level after 3 hours of administration. After single and multiple doses, the pharmacokinetic characteristics of valacyclovir and acyclovir were similar. The binding rate of acyclovir to plasma proteins is very low (15%).
After single and multiple doses of valacyclovir, acyclovir's plasma clearance half-life was approximately 3 hours. The amount of valacyclovir prototype in urine is less than 1% of the intake. Valacyclovir is mainly eliminated in the urine as acyclovir and the known acyclovir metabolite 9-carboxymethoxymethyl guanine (CMMG).
Pharmacokinetics in patients Herpes zoster and herpes simplex have no significant effect on the pharmacokinetic characteristics of valacyclovir and acyclovir after oral administration of this product.
In HIV-infected patients, the distribution and pharmacokinetic characteristics of acyclovir after a single or multiple doses of valacyclovir 1000 mg or 2000 mg showed no significant changes compared to healthy individuals.

Storage of valacyclovir hydrochloride tablets

Store below 30 ° C.

Packaging of valacyclovir hydrochloride tablets

10 pieces / box in aluminum-plastic packaging; 42 pieces / box.

Validity of valacyclovir hydrochloride tablets

36 months.

Implementation of valacyclovir hydrochloride tablets

Import drug registration standard JX20040245

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