Acyclovir

Acyclovir is an antiviral medication designed to treat infections caused by certain types of viruses. It is most often used to fight herpes viruses, such as herpes simplex virus (HSV) types 1 and 2, which cause oral and genital herpes, and varicella-zoster virus and herpes zoster.

Acyclovir specifically interacts with viral enzymes, which makes it particularly effective against herpes viruses. After entering the body, acyclovir is converted into an active form, acyclovir triphosphate, through the action of viral enzymes. This activated form is incorporated into the DNA of the virus, blocking its ability to reproduce further.

Indications Acyclovir

1. Herpessimplex (Herpes simplex): Acyclovir is used to treat primary and recurrent infections with herpes, which can manifest as herpetic stomatitis (appearance of problems in the mouth area), herpetic genital herpes (in the genital area), herpetic keratitis (in the eyes), and other forms.
2. Shingles (Herpes zoster): Acyclovir is used to treat shingles caused by the Varicella zoster virus. This condition is characterized by the appearance of a painful rash, usually located along the nerve.
3. Chickenpox (Varicella): Acyclovir can be used to treat chickenpox in adults and children.
4. Prevention of recurrences: The drug can be used to prevent recurrent infections in patients with weakened immune systems.
5. Prevention of HIV-associated infections: In patients with HIV infection, acyclovir may be prescribed to prevent certain herpetic infections such as herpetic stomatitis or genital herpes.

Release form

1. Tablets: This is the most common form and is intended to be taken orally. Tablets contain a specific dosage of acyclovir and are usually taken with water.
2. Cream or ointment: This form is intended for external application and is used to treat herpetic rashes on the skin and mucous membranes.
3. Eye ointment: To treat herpetic conjunctivitis or other eye infections, acyclovir may be used in the form of a special ointment that is applied to the inner surface of the eyelids.
4. Solution for injection: In some cases, such as serious or widespread infections, acyclovir may be given intravenously as a solution for injection.

Pharmacodynamics

1. Inhibition of viral DNA polymerase: The main mechanism of action of acyclovir is its ability to inhibit viral DNA polymerase, which is responsible for viral DNA replication. Acyclovir is incorporated into the viral DNA strand as a false nucleotide, resulting in the cessation of further viral DNA synthesis.
2. Selectivity to viral cells: Acyclovir is activated by phosphorylation in the cell infected by the virus, and therefore its action is directed mainly at viral cells. This minimizes the toxicity of the drug to normal cells of the body.
3. Reducing the duration and severity of infection: Use of acyclovir can reduce the duration and severity of infection caused by HPV and STDs and reduce the risk of complications.
4. Prevention of recurrences: Acyclovir is also effective in preventing recurrences of infection, especially when taken intermittently over a long period of time.
5. Reducing the likelihood of transmission: Use of acyclovir may also reduce the likelihood of transmission from an infected person to a healthy person.

Pharmacokinetics

1. Absorption: After oral administration of acyclovir it is well absorbed from the gastrointestinal tract. Absorption may be slowed by concomitant intake of food, so the drug is most often taken 1 hour before a meal or 2 hours after a meal.
2. Distribution: Acyclovir has a low volume of distribution in the body, approximately 1.6-2.0 L/kg. It penetrates well into many tissues and organs, including the brain, liver, kidney, lungs, skin and eyes.
3. Metabolism: Acyclovir is minimally metabolized. Most of the dose is excreted unchanged through the kidneys.
4. Excretion: About 60-90% of the administered dose of acyclovir is excreted by the kidneys in unchanged form, mainly within the first 24 hours after administration.
5. Half-life: The half-life of acyclovir from the body is approximately 2-3 hours in adults with normal renal function. This time may be longer in patients with impaired renal function.
6. Dosing: Acyclovir dosing may be modified in patients with impaired renal function to avoid accumulation of the drug in the body and minimize the risk of toxic effects.
7. Pharmacokinetics in different dosage forms: For ointments, creams and gels applied to the skin, bioavailability of acyclovir in topical application is low. When administered intravenously, its bioavailability is close to 100%.

Dosing and administration

Method of administration and dosage for oral administration:

1. Herpes simplex (HSV-1 and HSV-2):

   • Adults: Usually 200 mg 5 times a day for 7-10 days. In case of recurrent infection or to suppress chronic infection, the dose may be reduced to 400 mg twice daily.
   • Children: Dosage for children may vary and should be determined by a physician.

2. Herpes zoster (varicella-zoster):

   • Adults: 800 mg 5 times a day for 7-10 days.
   • Children: Recommendations may vary, consultation with a physician is mandatory.

3. Herpes prophylaxis in immunosuppressed patients:

   • Adults and children: Doses may vary; usually 200 mg 4 times daily.

For external use:

• Herpes simplex (lips and genitalia):
  • The cream or ointment is applied to the affected areas of the skin 5 times a day for 4-10 days.

For injection:

• Used mainly in hospital settings for severe infections, the dosage and route of administration depends on the severity of the condition and the doctor's judgment.

Important Notes:

• It is advisable to start taking acyclovir as soon as possible after the first symptoms of infection appear.
• Adequate hydration should be maintained during treatment.
• The dosage and duration of treatment may be adjusted by the physician depending on the clinical picture and response to treatment.
• Patients with renal impairment may require dose adjustment.

Use Acyclovir during pregnancy

1. Genital herpes:

   • In cases of primary genital herpes or severe recurrences during pregnancy, acyclovir may be prescribed to reduce the risk of transmission to the newborn. Infection of newborns with herpes can be serious and entail severe complications.

2. Prevention and treatment:

   • Acyclovir may be used to prevent recurrent herpes in pregnant women, especially in the third trimester, to reduce the likelihood of active herpes during labor, potentially requiring a cesarean section.

3. Risk and Benefit Assessment:

   • The prescribing of acyclovir during pregnancy should be based on a careful assessment of the balance of potential risks and benefits. This includes taking into account the severity of the infection, the stage of pregnancy and the general health of the pregnant woman.

Precautions:

• Monitoring:

  • If acyclovir is used during pregnancy, regular medical monitoring of maternal and fetal health is important.

• Dosage:

  • The lowest effective dose that provides infection control to minimize fetal exposure should be used.

• Consultation with a physician:

  • All questions regarding the use of acyclovir or any other medication during pregnancy should be discussed with your doctor, who can take all individual factors into account and recommend the safest and most effective treatment options.

Contraindications

1. Individual intolerance or allergy: People with known individual intolerance to acyclovir or any other component of the drug should avoid its use.
2. Pregnancy and breastfeeding: The use of acyclovir during pregnancy and breastfeeding should be coordinated with a doctor. Usually, the use of acyclovir during this period is possible, but requires caution and assessment of potential risks and benefits.
3. Hepatic insufficiency: In the presence of serious liver disease, dosage adjustment or complete withdrawal from the drug may be required.
4. Kidney disease: Patients with impaired renal function may require dosage adjustment of acyclovir.
5. Immunodeficiency states: In patients with immune system disorders such as HIV infection or taking immunosuppressive drugs, acyclovir may be contraindicated or require special caution.
6. Pediatric age: The safety and efficacy of acyclovir in children under 2 years of age have not been established.
7. Caution when used with other medicines: Acyclovir may interact with some other medicines, so you should discuss possible risks and side effects with your doctor, especially if you are taking other medicines.

Side effects Acyclovir

Common side effects

• Headache and fatigue are common symptoms that can occur when taking acyclovir.
• Nausea and vomiting, as well as diarrhea and abdominal pain, are common when taking acyclovir orally.

Side effects of topical application

• Redness, itching or burning at the site of application of the cream or ointment, which is usually temporary and goes away when you stop using the medicine.

Side effects during intravenous administration

• Inflammation of veins at the injection site, which can lead to pain.
• More serious reactions may include kidney damage and elevated liver enzymes, especially at high doses or in patients with prior kidney disease.

Rare and serious side effects

• Allergic reactions such as rashes, hives, Quincke's edema, and even anaphylactic shock.
• Neurologic reactions such as dizziness, disorientation, hallucinations, seizures, anxiety and tremor. These reactions are more common in patients with impaired renal function or in those receiving high doses of the drug.
• Thrombocytopenia (lowered platelet count) and leukopenia (lowered white blood cell count), which can affect the body's ability to resist infections.

Overdose

1. Toxic effect on kidneys: In case of acyclovir overdose renal failure may develop due to the formation of acyclovir crystals in the kidneys, which leads to their damage. This is especially likely if kidney function is impaired at the same time.
2. Central nervous system (CNS) symptoms: May include headache, drowsiness, slowed thinking, seizures, and coma.
3. Gastrointestinal disorders: Nausea, vomiting, diarrhea and abdominal pain may occur.
4. Electrolyte balance disorders: Hyperkalemia or hyponatremia may develop.
5. Allergic Reactions: Urticaria, pruritus, edema, angioedema and anaphylaxis may occur.

Interactions with other drugs

1. Probenicide: Probenicide may increase the concentration of acyclovir in the blood by delaying its elimination from the body, which may lead to an increase in its therapeutic effect and an increased risk of toxicity.
2. Mycophenolate mofetil: Acyclovir may decrease the blood concentration of mycophenolate mofetil by accelerating its metabolism in the liver, which may reduce its efficacy as an immunosuppressant.
3. Drugs causing nephrotoxicity: In combination with drugs such as aminoglycoside antibiotics or cyclosporine, acyclovir may increase the risk of nephrotoxic effects, especially in patients with impaired renal function.
4. Drugs affecting renal function: In combination with drugs that may affect renal function, such as certain non-steroidal anti-inflammatory drugs or diuretics, there may be an increase in the toxic effect of acyclovir on the kidneys.
5. Cimetidine and anti-inflammatory drugs containing COX-2 inhibitors: These drugs may increase the concentration of acyclovir in the blood due to the delay of its metabolism in the liver, which may lead to an increase in its therapeutic effect and an increased risk of toxicity.
6. Drugs causing hepatotoxicity: Acyclovir may increase the hepatotoxic effect of some drugs, such as paracetamol or protease inhibitors, which may lead to the development of liver failure.
7. Drugs causing hyperkalemia: In combination with drugs that increase blood potassium levels, such as spironolactone or angiotensin-converting enzyme inhibitors (ACEIs), an increase in hyperkalemia may occur.