This document provides information on acyclovir, an antiviral medication. It discusses acyclovir's class and structure, pharmacokinetics, mechanism of action in inhibiting viral DNA synthesis, uses for treating herpes viruses and varicella zoster virus, dosage recommendations for adults and pediatrics with considerations for renal impairment and immunocompromised patients, common side effects involving gastrointestinal, renal and nervous systems, and major drug interactions to avoid combining acyclovir with cidofovir, sirolimus, tacrolimus or tizanidine due to risk of kidney damage.

1. AcycWlToempIvlNatierT ER
Antiviral

2.  Ayclovir class & structure.
Pharmacokinetics
Mechanism of Action.
Uses.
 Dosage .
Side Effects
Interaction .
Contents

3. Category :Antiviral Agent
Class:Imidazopyrimidines
Subclass: Purines and Purine
Derivatives
IUPAC Name:2-amino-9-[(2-hydroxyethoxy)methyl]-6,9-dihydro-3H-purin-
Ayclovir class & structure.
6-one

4. Route of elimination: Primarily excreted
unchanged by the kidneys via active
tubular secretion.
Poorly water soluble and has poor
oral bioavailability (15–30%)
Half-life: 2.5-3.3 hours
Pharmacokinetics

5. Aciclovir is converted by
viral thymadine kinase
to aciclovir
monophosphate
which is then ↓ converted
by host cell kinases to
Aciclovir triphosphate
competitively inhibits
and inactivates HSV-specified
DNA polymerases
* preventing further
viral DNA synthesis
without affecting the
normal cellular
processes. Mechanism of action

6. Acyclovir is used to decrease pain and
speed the healing of sores or blisters in
people who have:
Varicella (chickenpox))
 Herpes zoster (shingles; a rash that can occur
in people who have had chickenpox in the past)
 First-time or repeat outbreaks of genital herpes
(a herpes virus infection that causes sores to
form around the genitals and rectum from time to
time)
Indications

7. Dosage

8. Adult
dose
for Herpes Simplex - Mucocutaneous/Immunocompetent Host:
Initial episode or intermittent therapy: 200 mg orally every 4 hours (5 times a day)
for 10 days
Alternatively, the US Centers for Disease Control and Prevention (CDC)
recommends 400 mg orally 3 times a day or 200 mg orally 5 times a day for 7 to 10
days.
Recurrent episodes: 200 mg orally every 4 hours (5 times a day) for 5 days
Alternatively, the CDC recommends 400 mg orally 3 times a day for 5 days, 800 mg
orally twice a day for 5 days, or 800 mg orally 3 times a day for 2 days.
Orolabial HSV infection treatment: 400 mg orally 5 times a day for 5 days
IV:
Severe initial episode: 5 to 10 mg/kg IBW IV every 8 hours for 5 to 7 days

9. Adult
dose
for Herpes Simplex - Mucocutaneous/Immunocompromised Host:
Treatment:
Oral: 400 mg orally every 8 hours for 7 to 14 days
IV: 5 mg/kg IV every 8 hours for 7 to 14 days
Treatment dosages recommended by the CDC.
Episodic outbreaks: 200 mg orally every 4 hours (5 times a day) for 5 to
10 days
Alternatively, the CDC recommends 400 mg orally 3 times a day for 5 to
10 days or 7 to 14 days
Orolabial HSV infection treatment:
HIV-infected patients: 400 mg 3 times a day for 7 to 14 days; dosage
recommended by the CDC

10. Adult
dose
For Herpes Simplex Encephalitis:
10 to 15 mg/kg IBW IV every 8 hours for 10 to 21 days
For Herpes Simplex – Suppression:
Chronic suppressive therapy:
Immunocompetent patient: 400 mg orally twice a day; alternatively, 200 mg
orally 3 to 5 times a day may be used
HIV-infected patient: 200 mg orally 3 times a day or 400 mg orally 2 times
a day
HIV-infected patient, genital herpes: 400 to 800 mg orally 2 to 3 times a
day

11. For Herpes Zoster:
Acute herpes zoster:
800 mg orally every 4 hours (5 times a day) for 7 to 10 days
Severe, immunocompromised host: 10 mg/kg IBW IV every 8 hours for 7
to 14 days
Therapy should be initiated within 72 hours after onset of rash, although,
during clinical trials, acyclovir was most effective when initiated within the
first 48 hours.

12. Adult
dose
For Varicella-Zoster:
Chickenpox:
Immunocompetent host: 800 mg orally four times a day for 5 days
Immunocompromised host: 10 mg/kg IBW IV every 8 hours for 7 to 10 days
or until no new lesions for 48 hours; after fever abates and if there is no proof
of visceral involvement, the patient may be switched to 800 mg orally four
times a day
Therapy should be initiated at the earliest sign of chickenpox, no later than
24 hours after onset of rash.

13. Pediatric dose
For Herpes Simplex - Mucocutaneous/Immunocompetent Host:
3 months to 11 years:
Initial episode: 10 to 20 mg/kg orally 4 times a day or 8 to 16 mg/kg
orally 5 times a day for 7 to 10 days
The American Academy of Pediatrics (AAP) recommends 40 to 80
mg/kg orally per day in 3 to 4 divided doses for 5 to 10 days.
Maximum dose: 1 g per day
12 years or older, over 40 kg:
Initial episode, severe initial episode, and recurrent episodes: Adult
dose

14. Pediatric dose
For Herpes Simplex - Mucocutaneous/Immunocompromised Host:
Treatment of mucocutaneous HSV infection:
Oral: 1 g orally per day in 3 to 5 divided doses for 7 to 14 days; dosage
recommended by the AAP
IV:
3 months to 11 years: 5 to 10 mg/kg or 250 to 500 mg/m2 IV every 8 hours
for 7 to 14 days
12 years or older, over 40 kg: Adult dose

15. Pediatric dose
For Herpes Simplex Encephalitis:
3 months to 11 years: 10 to 20 mg/kg or 500 mg/m2 IV every 8 hours for
10 to 21 days
12 years or older: Adult dose
For Herpes Simplex:
Neonatal HSV infection:
Less than 3 months: 10 to 20 mg/kg or 500 mg/m2 IV every 8 hours for
10 to 21 days
Some clinicians recommend 10 mg/kg every 12 hours for premature
neonates.

16. Pediatric dose
For Herpes Simplex – Suppression:
Oral:
Less than 12 years: 80 mg/kg/day orally in divided doses 3 to 4 times a day, not
to exceed 1 g/day
12 years or older: Adult dose
Immunocompromised host: 5 mg/kg IV every 8 or 12 hours or 250 mg/m2 IV
every 8 hours during risk period
Oral acyclovir prophylaxis is recommended by the U.S. Public Health Service and
Infectious Diseases Society of America for chronic suppressive therapy in HIV-infected
individuals, including infants and children, with frequent or severe
recurrences. Daily suppressive therapy reduces but does not eliminate
asymptomatic viral shedding, thus the extent to which it may prevent transmission
of infection to others is unknown.

17. Pediatric dose
For Herpes Zoster:
Oral:
Immunocompetent host:
12 years or older: 800 mg orally every 4 hours (5 times a day) for 5 to 10
days
HIV-infected host: 20 mg/kg (up to 800 mg per dose) orally 4 times a day for
7 to 10 days; dosage recommended by the CDC
IV:
Immunocompetent host:
Less than 1 year: 10 mg/kg IV every 8 hours for 7 to 10 days
1 year to 11 years: 10 to 20 mg/kg or 500 mg/m2 IV every 8 hours for 7 to
10 days
12 years or older: Adult dose
Immunocompromised host:
Less than 12 years: 10 to 20 mg/kg IV every 8 hours for 7 to 10 days
12 years or older: 10 mg/kg IV every 8 hours for 7 to 10 days

18. Pediatric dose
For Varicella-Zoster:
Chickenpox:
Immunocompetent host:
2 years or older, 40 kg or less: 20 mg/kg orally 4 times a day for 5
days (maximum: 3200 mg/day)
2 years or older, over 40 kg: Adult dose
Immunocompromised host:
Oral:
HIV-infected host: 20 mg/kg (up to 800 mg per dose) orally 4 times a
day for 7 days or until no new lesions for 48 hours
IV:
Less than 1 year: 10 mg/kg every 8 hours for 7 to 10 days or until no
new lesions for 48 hours
1 year to 12 years: 10 to 20 mg/kg or 500 mg/m2 IV every 8 hours for
7 to 10 days or until no new lesions for 48 hours
12 years or older: Adult dose

19. Renal dose adjustment
Adult & adolescents HIV-infected host
Oral:
Normal dose 200 mg every 4 hours:
CrCl less than 10 mL/min/1.73 m2: 200 mg every 12
hours
Normal dose 400 mg every 12 hours:
CrCl less than 10 mL/min/1.73 m2: 200 mg every 12
hours
Normal dose 800 mg every 4 hours:
CrCl 10 to 25 mL/min/1.73 m2: 800 mg every 8
hours
CrCl less than 10 mL/min/1.73 m2: 800 mg every 12
hours
Oral:
(based on normal dosage of 200 to 800 mg
orally every 4 to 6 hours):
CrCl 50 to 80 mL/min/1.73 m2: 200 to 800 mg orally
every 6 to 8 hours
CrCl 25 to 50 mL/min/1.73 m2: 200 to 800 mg orally
every 8 to 12 hours
CrCl 10 to 25 mL/min/1.73 m2: 200 to 800 mg orally
every 12 to 24 hours
CrCl less than 10 mL/min/1.73 m2: 200 to 400 mg
orally every 24 hours
IV:
CrCl 25 to 50 mL/min/1.73 m2: 100% of normal
dose every 12 hours
CrCl 10 to 25 mL/min/1.73 m2: 100% of normal
dose every 24 hours
CrCl less than 10 mL/min/1.73 m2: 50% of normal
dose every 24 hours
IV:
CrCl 10 to 50 mL/min/1.73 m2: 5 mg/kg IV every 12
to 24 hours
CrCl less than 10 mL/min/1.73 m2: 2.5 mg/kg every
24 hours

20. Dosage
precautions
Acyclovir has been associated with renal failure, in some cases fatal. Patients
receiving acyclovir should be adequately hydrated to prevent renal toxicity
secondary to crystalluria. Intravenous acyclovir should not exceed a
concentration of 7 mg per mL and should be infused over one hour to
minimize crystallization of drug in renal tubules.
Dosage adjustment is recommended when using Acyclovir in patients with
renal impairment.
Acyclovir should be used with caution in patients receiving other potentially
nephrotoxic agents since the concomitant use will increase the risk of renal
dysfunction and/or the risk of reversible central nervous system side effects.
Adequate hydration should be maintained.

21. Side Effect

22. • Gastrointestinal side
effects:
• have been the most
frequently reported include
nausea, vomiting,
abdominal pain, and
diarrhea. Nausea and
vomiting have been
reported with oral and
intravenous administration,
and have preceded
neurotoxicity and
nephrotoxicity.
• Gagging and anorexia .
• Renal side effects:
• have included renal failure,
renal pain ,elevated blood urea
nitrogen, elevated serum
creatinine, and hematuria.
• Renal effects generally are
transient and resolve over
several days following
discontinuation of therapy;
however fatal renal failure has
occurred.
• Renal damage is most
commonly due to crystallization
of the drug in the renal tubules.
• Elderly or renally impaired
patients are at greater risk for
developing neurotoxicity and
further deterioration in renal
function.

23. Nervous system side effects :
have included aggressive
behavior, agitation, ataxia, coma,
confusion, decreased
consciousness, delirium,
delusions, disorientation,
dizziness, EEG changes,
hallucinations, headache,
insomnia, irritability,
lightheadedness, major
depression, mania, psychosis
Local adverse effects :
associated with intravenous
administration of acyclovir have
included inflammation or phlebitis
at the injection site.
Phlebitis is more common when
concentrated solutions (greater
than 7 mg/mL) are administered.
Skin eruptions have been
reported at venipuncture sites and
tissue necrosis has occurred after
infiltration into extravascular
tissues.

24. • Cardiovascular side
effects have included
hypotension.
• Dermatologic side
effects: have included
alopecia, erythema
multiforme, hives,
photosensitive rash,
pruritus, rash, Stevens-
Johnson syndrome, toxic
epidermal necrolysis, and
urticaria.
• Hematologic and
lymphatic side effects:
• have included anemia,
disseminated intravascular
coagulation, hemolysis,
leukocytoclastic vasculitis,
leukocytosis, leukopenia,
lymphadenopathy,
neutropenia, neutrophilia,
thrombocytosis
• Hepatic side effects:
• have included elevated liver
function tests, hepatitis,
hyperbilirubinemia.

25. • Ocular side effects: have included visual
abnormalities.
• Musculoskeletal side effects : reported
have included myalgia and dysarthria.
• Other side effects: have included
angioedema, fever, malaise, pain, fatigue,
peripheral edema, and increased lactate
dehydrogenase , crystalluria.

26. Interactions

27. A total of 49 drugs are known to interact
with acyclovir:
 4 major drug interactions
(10 brand and generic names)
 22 moderate drug interactions
(62 brand and generic names)
 23 minor drug interactions
(107 brand and generic names)

28. These are 4 drugs known to have a major
interaction with acyclovir:
Cidofovir
Sirolimus
Tacrolimus
Tizanidine

29. Acyclovir ↔ Cidofovir
Using Cidofovir together with Acyclovir is not
recommended.
Cidofovir may cause kidney damage, and combining it
with other medications that can also affect the kidney
such as Acyclovir may increase that risk.
If patient has been receiving Acyclovir, he may need to
wait at least seven days after his last dose before he
can start treatment with Cidofovir
Interaction may cause kidney damage symptoms
such as nausea, vomiting, loss of appetite, increased
or decreased urination, sudden weight gain or weight
loss, fluid retention, swelling, shortness of breath,
muscle cramps, tiredness, weakness, dizziness,
confusion, and irregular heart rhythm.

30. Acyclovir ↔ Sirolimus
Sirolimus may cause kidney problems, and combining
it with other medications that can also affect the
kidney such as Acyclovir may increase that risk.
But patient may need a dose adjustment or more
frequent monitoring by his doctor to safely use both
medications. Interaction may cause symptoms that
may suggest kidney damage such as nausea,
vomiting, loss of appetite, increased or decreased
urination, sudden weight gain or weight loss, fluid
retention, swelling, shortness of breath, muscle
cramps, tiredness, weakness, dizziness, confusion,
and irregular heart rhythm.

31. Acyclovir ↔ Tizanidine
Using Tizanidine together with acyclovir is generally
not recommended. Combining these medications
may significantly increase the blood levels and
effects of Tizanidine .
This may cause blood pressure to fall excessively,
especially when patient rise from a sitting or lying
position.
The risk of other side effects such as drowsiness,
dizziness, lightheadedness, and fainting may also
increase.

32. http://www.drugs.com/dosage/acyclovir.html (Dosage )
http://www.drugs.com/drug-interactions/acyclovir.html
http://www.drugs.com/drug-interactions/acyclovir-index.html?
filter=3&generic_only=1#
http://www.drugs.com/drug-interactions/acyclovir-with-cidofovir-100-0-666-
0.html
http://www.drugs.com/drug-interactions/acyclovir-with-tizanidine-100-0-2205-
0.html (Interaction )
http://www.nlm.nih.gov/medlineplus/druginfo/meds/a681045.html(Indication)
http://www.drugs.com/sfx/acyclovir-side-effects.html (Side effects)
References