Acyclovir

• Acyclovir treats the first outbreak of genital herpes.
• Acyclovir suppresses frequent recurrences of genital herpes (six or more episodes per year) when taken continuously.
• Acyclovir can be taken intermittently at the first sign of a genital herpes recurrence in patients with infrequent, severe episodes.
• Acyclovir treats acute herpes zoster (shingles) in adults with normal immune function, reducing viral shedding, speeding healing, and reducing pain when started early.

• Animal studies of acyclovir have generally been negative for birth defects, though one non-standard rat study showed fetal abnormalities at high doses along with maternal toxicity.
• A long-running pregnancy registry tracking women exposed to acyclovir has not shown an increased rate of birth defects compared with the general population.
• Acyclovir should be used during pregnancy only if the potential benefit justifies the possible risk to the fetus, since acyclovir can cause chromosome breaks in cell cultures at high concentrations.

• Acyclovir passes into breast milk at levels that can be higher than the mother's own blood levels, so it should be used with caution while breastfeeding.

• Older adults are more likely to have reduced kidney function, so the dose may need to be lowered based on kidney function.
• Older adults and patients with kidney problems have a higher risk of neurological side effects such as confusion or drowsiness, and should be monitored closely.
• Adequate fluid intake should be maintained in older adults taking high oral doses of acyclovir.

• Safety and effectiveness of oral acyclovir have not been adequately studied in children under 2 years of age.
• In children old enough to be studied, acyclovir's pharmacokinetics are similar to those in adults.

• For a first episode of genital herpes, the usual dose is 200 mg every 4 hours, five times a day, for 10 days.
• For suppression of recurrent genital herpes, the usual starting dose is 200 mg three times daily, which can be increased to five times daily, or changed to 400 mg twice daily, if breakthrough occurs; the need for ongoing suppressive therapy should be reassessed periodically.
• For intermittent (episodic) treatment of a genital herpes recurrence, the dose is 200 mg every 4 hours, five times a day, for 5 days, started at the very first sign of an outbreak.
• For herpes zoster (shingles), the usual dose is 800 mg every 4 hours, five times a day, for 7 to 10 days, started within 72 hours of the rash appearing, ideally within 48 hours, for the greatest benefit.
• The dose must be reduced and the interval lengthened in patients with reduced kidney function, based on creatinine clearance.
• Patients on hemodialysis should receive an extra dose after each dialysis session, since dialysis removes a significant amount of the drug; no extra dose is needed with peritoneal dialysis.
• If a dose is missed, it should be taken as soon as remembered, then the regular dosing schedule resumed.

If overdose is suspected, seek emergency medical attention immediately or contact your regional Poison Control Centre without delay.

• Overdose can cause nausea, vomiting, headache, and confusion, especially with repeated excess doses over several days.
• Very high intravenous exposure has caused kidney injury, shown by rising creatinine and blood urea nitrogen, and can progress to kidney failure.
• Very high intravenous exposure has also caused confusion, hallucinations, agitation, seizures, and coma.
• Activated charcoal may help remove unabsorbed drug still in the gut.
• Hemodialysis significantly increases removal of acyclovir from the blood and may be used to manage a symptomatic overdose or to support recovery of kidney function if kidney failure occurs.

• Headache may occur, and is one of the most frequently reported side effects.
• Nausea may occur, and is one of the most frequently reported side effects.
• Vomiting may occur.
• Diarrhea may occur.
• A general feeling of being unwell (malaise) may occur.
• Rash may occur.
• Tingling or numbness (paresthesia) may occur.
• Weakness or fatigue (asthenia) may occur.
• Dizziness may occur.
• Loss of appetite, abdominal pain, constipation, or gas may occur.
• Sore throat may occur.
• Trouble sleeping (insomnia) may occur.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Acyclovir can cause kidney problems, including reversible kidney impairment or acute kidney failure, particularly with inadequate fluid intake or high doses.
• Acyclovir can cause neurological effects such as confusion, agitation, tremor, difficulty speaking, hallucinations, psychotic symptoms, seizures, extreme drowsiness, or coma, more often in older adults or those with kidney impairment.
• Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), a serious blood clotting disorder, has occurred in immunocompromised patients taking acyclovir and has been fatal in some cases.
• Severe allergic reactions, including angioedema, difficulty breathing, and anaphylaxis, can occur.
• Severe skin reactions, including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported.
• Blood cell abnormalities, including anemia, low white blood cell counts (leukopenia), and low platelet counts (thrombocytopenia), have been reported.
• Liver problems, including elevated liver enzymes, hepatitis, and jaundice, have been reported.
• Hair loss (alopecia) has been reported.
• In severely immunocompromised patients, prolonged or repeated courses of acyclovir may lead to resistant virus strains that do not respond to further treatment.
• Seek immediate medical attention for confusion, seizures, severe drowsiness, decreased urination, unusual bruising or bleeding, or signs of a severe allergic or skin reaction.

• Use with caution in patients with reduced kidney function, with the dose adjusted based on creatinine clearance.
• Use with caution in older adults, who are more likely to have reduced kidney function and a higher risk of neurological side effects.
• Use with caution in patients taking other drugs that can affect the kidneys, since this may increase the risk of kidney problems.
• Use with caution in severely immunocompromised patients, who are at higher risk of TTP/HUS and of developing acyclovir-resistant virus with prolonged or repeated use.
• Maintain adequate fluid intake in patients taking high oral doses of acyclovir to reduce the risk of kidney problems.
• Use with caution when driving or operating machinery until the individual effects of acyclovir are known, since a detrimental effect cannot be ruled out.
• Suppressive therapy should be reserved for patients with frequent, severe recurrences, and the need for continued therapy should be reassessed periodically.

• Contraindicated in patients with known hypersensitivity to acyclovir, valacyclovir, or any ingredient in the tablet.

• Probenecid can raise acyclovir blood levels by reducing its clearance through the kidneys, though no dose adjustment is needed given acyclovir's wide safety margin.
• Cimetidine can raise acyclovir blood levels by a similar mechanism, though no dose adjustment is needed.
• Mycophenolate mofetil, an immunosuppressant used in transplant patients, can raise the blood levels of both itself and acyclovir when taken together, though no dose adjustment is needed.
• No other clinically significant drug-drug interactions have been identified with acyclovir.

• Acyclovir tablets can be taken with or without food; studies have shown no meaningful effect of food on how much acyclovir is absorbed.

• Space doses evenly around the clock as prescribed, such as every 4 hours while awake, to keep drug levels steady, and take with or without food as convenient.

• Store acyclovir tablets at room temperature, between 15°C and 30°C, in a dry place, protected from light and moisture, in a tightly closed container.

• Acyclovir works best when started as early as possible after symptoms begin, whether for a herpes outbreak or shingles.
• Drink plenty of fluids while taking acyclovir, especially at higher doses, to help protect the kidneys.
• Avoid touching active sores and take care to avoid spreading the virus to others, since herpes can spread even without visible symptoms.
• Contact a healthcare professional promptly if confusion, unusual drowsiness, or decreased urination develops.