DANOVIR [Acyclovir] 250 mg Powder for intravenous solution

DANOVIR

instructions for medical use of the medicinal product

Tradename

Danovir, Danovir

International non-proprietary name

Aciclovir, Aciclovir

Compound

Each vial contains:

active substance: acyclovir 250 mg

Excipients: sodium hydroxide, water for injection

Dosage form

Powder for solution preparation.

Pharmacotherapeutic group

Antiviral agent.

Pharmacological properties

Pharmacodynamics

Antiviral agent, a synthetic analogue of the purine nucleoside.

Has the ability to inhibit in vitro and in vivo Herpes simplex virus types 1 and 2, Varicella zoster virus, Epstein-Barr virus, cytomegalovirus. In cell culture, acyclovir has the most pronounced antiviral activity against Herpes simplex type 1 virus, followed in descending order of activity by: Herpes type 2 virus, Varicella zoster virus, Epstein-Barr virus and cytomegalovirus. The inhibitory effect of acyclovir on these viruses is characterized by high selectivity.

Aciclovir is not a substrate for the thymidine kinase enzyme in uninfected cells, so aciclovir has low toxicity to mammalian cells. The high selectivity of action and low toxicity to humans are due to the lack of the necessary enzyme for the formation of acyclovir triphosphate in intact cells of the macroorganism.

Thymidine kinase of cells infected with Herpes simplex viruses types 1 and 2, Varicella zoster virus, Epstein-Barr virus or cytomegalovirus, converts acyclovir to acyclovir monophosphate, a nucleoside analog, which is then sequentially converted to diphosphate and triphosphate by the action of cellular enzymes. Acyclovir triphosphate is integrated into the viral DNA chain and blocks its synthesis through competitive inhibition of the viral DNA polymerase. Thus, "defective" viral DNA is formed, which leads to suppression of the replication of new generations of viruses .

  Pharmacokinetics

Acyclovir is widely distributed in tissues and body fluids. Plasma protein binding is 9-33%. The concentration in the cerebrospinal fluid is about 50% of the corresponding concentration in the blood plasma at steady state. In adults, after intravenous administration, the final T1 / 2 is about 2.9 hours. In newborns (from 0 to 3 months), with the introduction of acyclovir at a dose of 10 mg / kg as an infusion over 1 hour every 8 hours, the final T1 / 2 is about 3.8 hours Excreted mainly in the urine unchanged. The only known urinary metabolite is 9-[(carboxymethoxy)methyl]guanine, which accounts for 10-15% of the urinary dose.

Indications for use

• treatment of infections caused by Herpes simplex virus types 1 and 2;

• prevention of infections caused by Herpes simplex virus types 1 and 2 in immunocompromised patients;

• treatment of infections caused by the Varicella zoster virus, including chickenpox and herpes zoster;

• treatment of infections caused by the Herpes simplex virus types 1 and 2 in newborns;

• prevention of cytomegalovirus infection in bone marrow transplant recipients.

Contraindications

• hypersensitivity to acyclovir or valaciclovir.

Dosage and administration

Intravenously.

adults

For infections caused by herpes simplex, chicken pox and shingles: 5 mg/kg body weight, after eight hours.

For infections caused by varicella-zoster and herpes zoster in immunocompromised patients or herpes encephalitis: 10 mg/kg body weight, after eight hours (except in patients with impaired renal function). The duration of treatment is five days. If necessary, therapy can be extended.

Children

The dose for children from 3 months to 12 years is calculated based on body surface area.

For infections caused by herpes simplex, chicken pox, and shingles: 250 mg/m2 body surface area, after eight hours.

For infections caused by varicella-zoster and herpes zoster in immunocompromised patients or herpes encephalitis: 500 mg/m2, after eight hours.

The duration of treatment is five days. If necessary, therapy can be extended.

Dosage for newborns from the first day of life to 3 months of age is calculated based on body weight. For infections caused by the herpes simplex virus: 10 mg/kg body weight, after eight hours, the usual duration of therapy is 10 days.

Patients with renal insufficiency

In patients with chronic renal failure, as well as in the elderly, dose adjustment is necessary: taking into account the level of creatinine clearance, reduce the dose by half or increase the interval.

Solution preparation method

The contents of 1 vial are diluted with a solvent. Sterile water for injection or 0.9% sodium chloride solution is used as a solvent. The solution can be administered as an injection slowly (within an hour) or applied drip, for which the resulting solution is diluted in an additional 50 ml of solvent.

Special instructions and precautions

An adequate level of body hydration should be maintained in patients receiving intravenous acyclovir.

The risk of developing renal failure increases with simultaneous use with other nephrotoxic drugs.

Acyclovir is excreted in the urine, therefore, in patients with impaired renal function, reduced doses of acyclovir should be used. In elderly patients, a decrease in renal function is possible, therefore, the need to reduce the dose of acyclovir for this group of patients should be evaluated. Both in elderly patients and in patients with impaired renal function, the risk of developing adverse reactions from the central nervous system is increased, therefore, such patients should be under close medical supervision for the timely detection of relevant symptoms.

In patients receiving higher doses of acyclovir (for example, with herpes encephalitis), renal function should be carefully monitored, especially against the background of dehydration or pre-existing impaired renal function.

Prolonged or repeated courses of acyclovir treatment in severely immunocompromised patients may result in acyclovir desensitized virus strains that will not respond to continued acyclovir therapy.

Use during pregnancy and during breastfeeding

Use during pregnancy is possible only if the intended benefit to the mother outweighs the potential risk to the fetus.

If necessary, taking the drug during lactation requires interruption of breastfeeding.

Interaction with other drugs

When mixing solutions, it is necessary to take into account the alkaline reaction of acyclovir for intravenous administration (pH=11).
Strengthening the effect is noted with the simultaneous appointment of immunostimulants.
Blockers of tubular secretion reduce tubular secretion of intravenously administered acyclovir, which can lead to an increase in the concentration of acyclovir in the blood serum and cerebrospinal fluid (CSF), slowing down the excretion of acyclovir (an increase in the half-life) from the blood and CSF, and increased toxic effects.

Other nephrotoxic drugs increase the risk of aciclovir nephrotoxicity.
Acyclovir is excreted unchanged through the kidneys by active tubular secretion. All drugs with a similar route of elimination can increase the plasma concentration of acyclovir. Thus, probenecid and cimetidine increase the AUC of acyclovir and reduce its renal clearance. However, dose adjustment is not required due to the wide range of therapeutic doses of acyclovir.
In patients receiving acyclovir, caution is required when prescribing drugs competing for the elimination pathway with it due to the potential increase in plasma concentrations of one, both drugs, or their metabolites. The combined use of acyclovir and mycophenolate mofetil (an immunosuppressive drug) used in organ transplantation leads to an increase in the AUC for acyclovir and the inactive metabolite of mycophenolate mofetil.
Serum lithium concentrations should be closely monitored when lithium is used concomitantly with high doses of intravenous acyclovir due to the risk of toxicity.
Monitoring (with monitoring for changes in renal function) is also required when intravenous acyclovir is administered with drugs that affect other aspects of renal physiology (eg, cyclosporine, tacrolimus).

Side effect

From the hemopoietic system: infrequently - anemia, leukopenia, thrombocytopenia.

From the immune system: very rarely - anaphylaxis.

From the nervous system: very rarely - headache, dizziness, agitation, confusion, tremor, ataxia, dysarthria, hallucinations, psychotic symptoms, convulsions, drowsiness, encephalopathy, coma.

From the side of the cardiovascular system: often - phlebitis.

From the respiratory system: very rarely - shortness of breath.

From the digestive system: often - nausea, vomiting; very rarely - diarrhea, abdominal pain.

From the side of the liver: often - a transient increase in the activity of hepatic transaminases; very rarely - a transient increase in the concentration of bilirubin, jaundice, hepatitis.

From the skin and subcutaneous tissues: often - itching, urticaria, rash (including photosensitivity); very rarely - angioedema.

From the urinary system: often - an increase in the concentration of urea and creatinine in the blood; very rarely - impaired renal function, acute renal failure, renal colic.

Other: very rarely - general weakness, fever, local inflammatory reactions. In case of accidental introduction of acyclovir into the extracellular space during intravenous infusion, severe local inflammatory reactions were detected, which can lead to destructive changes in the skin.

Overdose

Overdoses of the drug cause an increase in the concentration of serum creatinine, blood urea nitrogen and renal failure. Neurological symptoms include confusion, hallucinations, agitation, seizures, and coma. Hemodialysis significantly enhances the excretion of acyclovir from the blood, therefore it is indicated for an overdose of acyclovir.

Storage conditions

Store in a cool and dry place below ^250C .

Keep out of the reach of children!

Best before date

3 years. Do not use after the expiry date stated on the package.

Holiday conditions

Released by prescription.

Release form

5 bottles with instructions for use in a cardboard box.