What Are the Pros and Cons of Using Acyclovir for a Cold Sore?

Aciclovir injection is used for the treatment of herpes simplex virus infection, shingles and chickenpox in immunodeficiency patients.

Foreign name: Aciclovir Injection

Whether prescription drugs: prescription
Specifications: 5ml: 0.25g

Acyclovir injection composition:

Main ingredients: Acyclovir. Excipients: Sodium sulfite, sodium arsenate, sodium hydroxide, hydrochloric acid.

Acyclovir injection properties:

This product is white loose block or powder

Acyclovir injection indications

Herpes simplex virus infection: used for the treatment of primary and recurrent mucosal skin infections in immunodeficiency patients and the prevention of recurrent cases; it is also used for the treatment of herpes simplex encephalitis.
Shingles: Used for the treatment of diffuse shingles in patients with severe herpes zoster in immunodeficiency patients or those with normal immune function.
Treatment of chickenpox in immunocompromised persons.

Acyclovir injection dosage and dosage

For intravenous infusion only, each infusion time is more than 1 hour.
Usual Adult:
The initial treatment of severe genital herpes is 5mg / kg once per body weight (according to acyclovir, the same below), 3 times a day, once every 8 hours for a total of 5 days.
The skin and mucous membrane of herpes simplex or severe shingles in immunodeficiency patients should be 5-10mg / kg once per body weight, 3 times a day, and instilled once every 8 hours for 7-10 days.
Herpes simplex encephalitis, 10 mg / kg once per body weight, 3 times a day, instillation every 8 hours for a total of 10 days.
The maximum daily dose for adults is 30mg / kg for body weight or 1.5g / m2 for body surface area. Do not exceed 20 mg / kg every 8 hours.
Pediatric commonly used amount:
Primary treatment of severe genital herpes, infants and children under 12 years of age, 250mg / m ² according to body surface area (based on acyclovir, the same below), 3 times a day, once every 8 hours instillation for a total of 5 days.
Herpes simplex of skin and mucosa of immunodeficiency patients, infants and children under 12 years old, according to body surface area 250mg / m ² once, 3 times a day, once every 8 hours instillation, a total of 7 days, 12 years old or more as an adult.
Herpes simplex encephalitis, 10 mg / kg once per body weight, 3 times a day, instillation every 8 hours for a total of 10 days.
Those with immunodeficiency combined with chickenpox, 10 mg / kg once per body weight or 500 mg / m ² once per body surface area, 3 times a day, instillation once every 8 hours for a total of 10 days. The highest dose for children is 500 mg / m ² per body surface area every 8 hours.
Preparation of medicinal solution: Take a 0.9% sodium chloride injection or 5% glucose injection of this product and dilute it to at least 100ml, so that the final drug concentration does not exceed 7g / L, otherwise it may easily cause phlebitis. The prepared solution should be used within 12 hours, and precipitation in the refrigerator will occur.
This product cannot be diluted with benzyl alcohol-containing diluent. Patients with acute or chronic renal insufficiency should not use this product for intravenous infusion, because the drip rate may cause renal failure.

Acyclovir injection adverse reactions

Common adverse reactions: inflammation or phlebitis at the injection site, skin itching or urticaria, rash, fever, mild headache, nausea, vomiting, diarrhea, proteinuria, elevated blood urea nitrogen and serum creatinine, abnormal liver function such as Serum aminotransferase, alkaline phosphatase, lactate dehydrogenase, and total bilirubin were slightly elevated.
Rare adverse reactions are: acute renal insufficiency, decreased white blood cells and red blood cells, decreased hemoglobin, neutropenia, thrombocytopenic purpura, elevated cholesterol and triglycerides, hematuria, hypotension, sweating, palpitations, and dyspnea , Chest tightness, etc.
The clinically observed adverse reactions after the market of this product are:
Digestive system: including gastrointestinal cramps, diarrhea, anorexia, and more.
Systemic allergies: including fever, headache, angioedema, rash, and peripheral redness.
Central system: Includes headache, excessive excitement, irritability, delirium, ataxia, coma, confusion, dizziness, dizziness, headache, hallucinations, local nerve paralysis, tremor, drowsiness, etc. These symptoms can be significant, especially in older people.
Blood and lymphatic system: Including anemia, white blood cells and thrombocytopenia, lymphadenopathy, vasculitis, DIC, hemolysis, etc.
Hepatobiliary, pancreas: including hepatitis, hyperbilirubinemia, jaundice, etc.
Muscle and skeletal system: muscle pain response.
Skin: baldness, photosensitive rash, itching, Stevens-Johnson syndrome, toxic epidermal necrosis, rubella, erythema polymorpha, etc.
Special sensation: abnormal vision.

Acyclovir injection contraindications

Those who are allergic to acyclovir are disabled.

Precautions for acyclovir injection

caveat:
Renal damage can cause death when receiving acyclovir. Renal function should be checked before or during medication.
When patients with immune dysfunction receive acyclovir treatment, thrombosis, thrombocytopenic purpura, hemolysis, uremia syndrome (TT; / HUS) can occur and can lead to death.
Patients with acute or chronic renal insufficiency should not use this product for intravenous infusion, because the drip rate may cause renal failure.
Special care should be taken when using acyclovir in patients receiving potentially nephrotoxic drugs, as this may increase the risk of renal dysfunction and increase reversible central nervous system symptoms.
People allergic to ganciclovir may also be allergic to this product.
The following situations need to consider the advantages and disadvantages of medication: patients with dehydration, the dose of this product should be reduced. Patients with severe liver dysfunction, intolerance to this product, mental disorders, or previous psychotic reactions to cytotoxic drugs, this product is prone to produce mental symptoms and should be used with caution.
There are no data on the treatment of acute herpes zoster more than 72 hours before the start of treatment. Therefore, patients with herpes zoster should be treated as soon as possible.
Chickenpox: For healthy children, chickenpox is a self-limiting mild to moderate disease, while adolescents and adults are more severe. Treatment should be performed within 24 hours of the acute onset of chickenpox, and there is no effective treatment data to start treatment at the late stage of onset.
This product cannot eradicate the genital herpes infection. It has no obvious effect on latent infection and recurrence of herpes simplex virus. There is no information to prove whether this product can prevent the disease from being transmitted to others. Because genital herpes is a sexually transmitted disease, patients should avoid contact with the patient and avoid sexual intercourse to avoid infecting their spouse. Genital herpes can also be transmitted asymptomatically and excreted by asymptomatic viruses. If recurrent genital herpes is found, the patient should be treated as soon as the first symptoms or signs are found. Because most people with genital herpes are susceptible to cervical cancer, they should be checked at least once a year for early detection.
People with severe immune dysfunction may cause drug resistance after long-term application of this product. If herpes simplex patients have not improved their skin damage after applying this product, they should test the virus's sensitivity to this product.
Intravenous infusion should be slow, otherwise drug crystal precipitation in renal tubules can occur, which can cause renal function damage in up to 10% of cases, and do not let it leak out of blood vessels, so as not to cause pain and phlebitis.
2 hours after the intravenous infusion, the urine concentration is the highest. At this time, the patient should be given sufficient water to prevent the drug from depositing in the renal tubules.
One hemodialysis can reduce the blood drug concentration by 60%, so the dose should be repeated once every 6 hours of hemodialysis.
The dose for obese patients should be calculated based on standard weight. When dose adjustment is required, it can be adjusted based on creatinine clearance.
Disturbance to diagnosis: can cause renal tubular obstruction, increase serum creatinine and urea nitrogen. It is usually not caused by proper dosage and sufficient water.
This agent is alkaline. Mixing with other drugs can easily cause pH changes. Compatible use should be avoided as much as possible.
Information for patients: If you feel serious or annoying adverse reactions, those who are pregnant or preparing to become pregnant, women who are preparing to breastfeed, or patients with other problems, you should consult your doctor and use the medicine reasonably under the guidance of your doctor.

Acyclovir injection for pregnant and lactating women

Use with caution in pregnant women. An epidemiological record of the efficacy of acyclovir used by pregnant women established from 1984 to April 1994. Among 756 experimental results over a three-month period, 749 pregnant women took acyclovir systematically. Its teratogenic effect on infants is similar to that of the general population. But these data are not enough to prove that acyclovir is complete for pregnant women and fetuses. Acyclovir may only be considered when its effect on the fetus is far greater than its risk.
The concentration of acyclovir in milk is 0.6-4.1 times of its blood concentration. When breastfeeding women take a dose of 0.3mg / kg per day, it may affect infant development. Acyclovir may be used by breastfeeding women only if necessary.

Acyclovir injection for children

Although no special adverse reactions were found in children, they should be used with caution. Newborns should not use benzyl alcohol-containing dilutions to prepare infusions, otherwise it is likely to cause fatal syndromes, including acidosis, central depression, dyspnea, renal failure, hypotension, epilepsy and intracranial bleeding.

Acyclovir injection for the elderly:

There is no sufficient research data to show that the medication for the elderly over 65 years is significantly different from that for young people. In general, elderly people should be careful when choosing medications, choose a low-dose effective medication range, and minimize the occurrence of renal dysfunction or other side effects caused by increasing the number of medications.

Acyclovir injection drug interactions

When combined with interferon or methotrexate (intrathecally) when administered intravenously, it may cause mental disorders and should be used with caution.

When combined with nephrotoxic drugs when administered intravenously, nephrotoxicity can be aggravated, especially in patients with renal insufficiency.

Combined with zidovudine can cause renal toxicity, manifested as deep lethargy and fatigue.

4. Competitively inhibits organic acid secretion with probenecid, combined with probenecid can slow down urinary tract excretion, prolong half-life, and accumulate drug volume in the body.

Acyclovir injection overdose

Overdose: There is no special antidote for this product. Symptomatic treatment and supportive therapy are mainly used: give sufficient water to prevent the drug from depositing in the renal tubules; hemodialysis helps excrete drugs in the blood, which is especially important for patients with acute renal failure and hematuria.

Taking a dose greater than 20 grams can cause excitement, agitation, coma, tremor, and weakness. Rapid intravenous injection is given too high doses, and acyclovir will cause secondary renal failure due to elevated creatinine and blood urea nitrogen due to crystalline accumulation (2.5mg / ml) due to its excessive concentration in renal tubules. Once renal failure and anuria occur, the patient must undergo hemodialysis until renal function is restored.

Pharmacology and Toxicology of Acyclovir Injection

Genotoxicity: 16 genotoxicity tests were performed, and no mutagenesis was seen in 4 microbiological studies; 2 in vitro cytogenetic tests on mouse lymphoma cells and human lymphocytes showed that this product was mutagenic effect. No mutagenic effects were observed in 5 in vitro cytogenetic tests (3 were Chinese hamster ovary cells and 2 were mouse lymphoma cells). Of the two in vitro cell transformation tests performed after administration of immunocompromised, weaning, and homologous pups, one of them was positive, showing that the cells changed morphologically to tumor cells, while in another In the test, the same results were not seen (the reason may be that the chromosome damage did not change significantly when the sensitive double dose was administered); the dominant lethal test in mice (at a dose of 36 to 73 times the human dose) was negative.

Reproductive toxicity: Mice (450mg / kg / day, PO) and rabbits (250mg / kg / day, SC) test results show that this product has no effect on its fertility and reproductive function. The plasma drug concentration of mice and rats is 9-18 times and 8-15 times that of human blood drug levels, respectively. When mice and rabbits were given higher doses (50 mg / kg / day, SC, 11-22 times and 16-31 times the human level, respectively), implantation could be reduced, but the size of littermates was not affected. The average corpus luteum, total implantation position, and surviving fetuses in the rats taking this product (50 mg / kg / day, SC) before and after delivery all decreased significantly.
Dogs were given this product for one month (50mg / kg / day, IV, 21 to 41 times the human dose) (blood concentration was 21 to 41 times that of humans) or for one year (60mg / kg / day, PO, 6-12 times the human dose), no testicular abnormalities were found. At higher doses to rats and dogs, testicular atrophy and sperm reduction can be seen.
The exposure doses given to mice (450 mg / kg / day, PO), rabbits (50 mg / kg / day, SC or IV) and rats (50 mg / kg / day, SC) were 9 to 18 doses for human use, respectively. At 16 to 106 and 11 to 22 times, no teratogenic effect was seen.
There are no adequate and strictly controlled studies in pregnant women, but an epidemiological survey showed that 756 pregnant women were followed up with systemic medications, and the incidence of birth defects in babies was similar to that of the general population, but these data are not enough to prove their effectiveness. Pregnant women and fetuses are safe. Only consider taking this product when its therapeutic effect on the fetus is far greater than its risk.
For lactating women, the concentration of this product in milk is 0.6 to 4.1 times its blood concentration. When the dosage of lactating women reaches 0.3mg / kg / day, the concentration may affect the infant. Therefore, caution should be used when lactating women, and only when necessary.
Carcinogenicity: During the entire life span of rats and mice, 450 mg / kg / day of this product was administered by gavage. The results showed that there was no statistically significant difference in the number of animals with tumors in the administration group and the control group. Reduce the latency of tumorigenesis. The maximum plasma concentrations in mice and rats are 3 to 6 times and 1 to 2 times the human dosage levels, respectively.
This product is a synthetic nucleoside antiviral drug that inhibits both herpes simplex virus type 1 (HSV-1), type II (HSV-2) and varicella-zoster virus (VZV) in vitro and in vivo. Cell culture results show that this product has the strongest effect on inhibiting HSV-1 virus, followed by HSV-2 and VZV viruses.
Since this product has affinity for thymidine kinase (TK) encoded by HSV and VZV, it has a highly selective inhibitory effect. Such viral enzymes convert acyclovir into acyclovir monophosphate, a nucleoside analog. Monophosphate is further converted into diphosphate by guanylate kinase in the cell, and then converted into triphosphate by various enzymes in the cell. In vitro, acyclovir triphosphate stops herpes virus DNA replication in three ways:
Competitively inhibits viral DNA polymerase;
Enter and terminate extended viral DNA strands;
Inactivate viral DNA polymerase. Compared with VZV, this product has stronger antiviral activity against HSV, which is due to the stronger phosphorylation of thymidine kinase (TK) of the virus.

Pharmacokinetics of Acyclovir Injection

Acyclovir can be widely distributed in various tissues and body fluids, including brain, kidney, lung, liver, small intestine, muscle, spleen, milk, uterus, vaginal mucosa and secretions, cerebrospinal fluid and herpes fluid. It is high in kidney, liver and small intestine, and the concentration in cerebrospinal fluid is about half of that in blood. Drugs can pass through the placenta. After 1 hour of intravenous infusion at 5 mg / kg and 10 mg / kg in healthy adults, the average steady-state blood drug concentrations were 9.8 mg / ml and 20.7 mg / ml, and after 7 hours, the trough concentrations were 0.7 mg / ml and 2.3, respectively. mg / ml. For children over one year old, the dosage of 250 mg / m ² is similar to that of adults at 5 mg / kg, while the dosage of 500 mg / m ^{2 is} similar to that of adults at 10 mg / kg.
The newborn (under 3 months of age) intravenously injects 10 mg / kg every 8 hours, and each infusion lasts for 1 hour. Its steady-state peak concentration (Cmax) is 13.8 g / ml, and the trough concentration is 2.3 g / ml. This product has a low protein binding rate (9% to 33%). In the liver, the main metabolites account for 9% to 14% of the dose, and are excreted through the urine. The blood elimination half-life (t _1/2/2 ) is about 2.5 hours. When the creatinine clearance rate is 50 to 80 ml / min and 15 to 50 ml / min, the blood elimination half-life (t _1/2/2 ) is 3.0 hours and 3.5 hours, respectively. The blood elimination half-life (t _1/2 ) of anuria was as long as 19.5 hours, and decreased to 5.7 hours during hemodialysis.
This product is mainly excreted by the kidney through glomerular filtration and tubular secretion. About 45% to 79% of the drug is excreted from the urine in its original form. The fecal excretion rate is less than 2%. Exhaled breath contains trace drugs. About 6 hours of hemodialysis removes about 60% of the drugs in the blood. Peritoneal dialysis clearance is small.