acyclovir

ay-SYE-kloe-veer

Therapeutic Classification: antivirals

Pharmacologic Classification: purine analogues

REMS

PO: Treatment of:
- Recurrent genital herpes infections,
- Localized cutaneous herpes zoster infections (shingles) and chickenpox (varicella).
IV: Treatment of:
- Severe initial episodes of genital herpes in nonimmunosuppressed patients,
- Mucosal or cutaneous herpes simplex infections or herpes zoster infections (shingles) in immunosuppressed patients,
- Herpes simplex encephalitis,
- Neonatal herpes simplex infections.
Topical Cream: Recurrent herpes labialis (cold sores). Ointment: Treatment of limited non-life-threatening herpes simplex infections in immunocompromised patients (systemic treatment is preferred).

Interferes with viral DNA synthesis.

Therapeutic effects:

Inhibition of viral replication, decreased viral shedding, and reduced time for healing of lesions.

Absorption: Despite poor absorption (15–30%), therapeutic plasma concentrations are achieved.

Distribution: Widely distributed. CSF concentrations are 50% of plasma.

Metabolism/Excretion: >90% eliminated unchanged by kidneys; remainder metabolized by liver.

Half-Life: Neonates: 4 hr; Children (1–12 yr): 2–3 hr; Adults: 2–3.5 hr (↑ in renal failure).

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1.5–2.5 hr	4 hr
IV	prompt	end of infusion	8 hr

‡Salivary concentrations

Contraindicated in:

Hypersensitivity to acyclovir or valacyclovir.

Use Cautiously in:

Pre-existing serious neurologic, hepatic, pulmonary, or fluid and electrolyte abnormalities;
Renal impairment (dose alteration recommended if CCr <50 mL/min);
Obese patients (dose should be based on ideal body weight);
Patients with hypoxia;
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk; systemic exposure minimal following buccal or topical administration;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant; systemic exposure minimal following buccal or topical administration;
Geri: May need to ↓ dose in older adults due to age-related ↓ in renal function.

Derm: acne, hives, rash, STEVENS-JOHNSON SYNDROME, unusual sweating

Endo: changes in menstrual cycle

F and E: polydipsia

GI: diarrhea, nausea, vomiting, ↑liver enzymes, abdominal pain, anorexia, hyperbilirubinemia

GU: crystalluria, hematuria, RENAL FAILURE, renal pain

Hemat: THROMBOTIC THROMBOCYTOPENIC PURPURA/HEMOLYTIC UREMIC SYNDROME (HIGH DOSES IN IMMUNOSUPPRESSED PATIENTS)

Local: pain, phlebitis, local irritation

MS: joint pain

Neuro: dizziness, headache, hallucinations, SEIZURES, trembling

Drug-drug:

Probenecid and theophylline may ↑ levels and risk of toxicity.
Valproic acid or phenytoin may ↓ levels and effectiveness.
Concurrent use of other nephrotoxic drugs may ↑ risk nephrotoxicity.
Zidovudine and intrathecal methotrexate may ↑ risk of CNS side effects.

Initial Genital Herpes

PO (Adults and Children ): 200 mg every 4 hr while awake (5 times/day) for 7–10 days or 400 mg every 8 hr for 7–10 days; maximum dose in children: 80 mg/kg/day in 3–5 divided doses.
IV (Adults and Children ≥12 yr): 5 mg/kg every 8 hr for 5 days.

Chronic Suppressive Therapy for Recurrent Genital Herpes

PO (Adults and Children ): 400 mg twice daily or 200 mg 3–5 times/day for up to 12 mo. Maximum dose in children: 80 mg/kg/day in 2–5 divided doses.

Intermittent Therapy for Recurrent Genital Herpes

PO (Adults and Children ): 200 mg every 4 hr while awake (5 times/day) or 400 mg every 8 hr or 800 mg every 12 hr for 5 days; start at first sign of symptoms. Maximum dose in children: 80 mg/kg/day in 2–5 divided doses.

Acute Treatment of Herpes Zoster in Immunosuppressed Patients

PO (Adults ): 800 mg every 4 hr while awake (5 times/day) for 7–10 days. Prophylaxis: 400 mg 5 times/day.
PO (Children ): 250–600 mg/m²/dose 4–5 times/day.

Herpes Zoster in Immunocompetent Patients

PO (Adults and Children ): 4000 mg/day in 5 divided doses for 5–7 days. Maximum dose in children: 80 mg/kg/day in 5 divided doses.

Chickenpox

PO (Adults and Children ): 20 mg/kg (not to exceed 800 mg/dose) 4 times daily for 5 days. Start within 24 hr of rash onset.

Mucosal and Cutaneous Herpes Simplex Infections in Immunosuppressed Patients

IV (Adults and Children >12 yr): 5 mg/kg every 8 hr for 7 days.
IV (Children 3 mo–12 yr): 10 mg/kg every 8 hr for 7 days.
(Adults ): ½-inch ribbon of 5% ointment for every 4-square-inch area every 3 hr (6 times/day) for 7 days.

Herpes Simplex Encephalitis

IV (Adults and Children ≥12 yr): 10 mg/kg every 8 hr for 10 days.
IV (Children 3 mo–12 yr): 20 mg/kg every 8 hr for 10 days.
IV (Children birth–3 mo): 20 mg/kg every 8 hr for 14–21 days.
IV (Neonates , premature): 10 mg/kg every 12 hr for 14–21 days.

Neonatal Herpes Simplex Infections

IV (Children postmenstrual age of ≥34 wk): 20 mg/kg every 8 hr for 21 days.
IV (Children postmenstrual age of <34 wk): 20 mg/kg every 12 hr for 21 days.

Varicella Zoster Infections in Immunosuppressed Patients

IV (Adults and Children ≥12 yr): 10 mg/kg every 8 hr for 7 days.
IV (Children <12 yr): 20 mg/kg every 8 hr for 7 days.

Renal Impairment

PO IV (Adults and Children >3 mo): CCr 25.1–50 mL/min/1.73 m²: Normal dose every 12 hr; CCr 10.1–25 mL/min/1.73 m²: Normal dose every 24 hr; CCr ≤10 mL/min/1.73 m²: 50% of dose every 24 hr.

Herpes Labialis

(Adults and Children >12 yr): Apply 5 times/day for 4 days; start at first symptoms.

(Generic available)

Tablets: 200 mg; 400 mg; 800 mg
Capsules: 200 mg
Oral suspension banana flavor: 200 mg/5 mL
Solution for injection: 25 mg/mL; 50 mg/mL
Cream: 5%
Ointment: 5%
In combination with: hydrocortisone (Xerese). See Appendix [not included in this PDA edition].

Assess lesions before and daily during therapy.
Monitor frequency of recurrences.
Monitor neurologic status in patients with herpes encephalitis or for encephalopathic changes such as lethargy, obtundation, tremors, confusion, hallucinations, agitation, or seizures. Initiate seizure precautions as indicated.

Lab Test Considerations:

Monitor BUN, serum creatinine, and CCr before and during therapy. May ↑ BUN and serum creatinine or ↓ CCr, which may indicate renal failure.

Do not confuse Zovirax with Zyvox or Zostrix.
Start acyclovir treatment as soon as possible after herpes simplex symptoms appear and within 24 hr of a herpes zoster outbreak.
PO: Acyclovir may be administered with food or on an empty stomach, with a full glass of water.
- Shake oral suspension well before administration.
Topical Apply to skin lesions only; do not use in the eye.

IV Administration:

IV: Maintain adequate hydration (2000–3000 mL/day), especially during first 2 hr after IV infusion, to prevent crystalluria.
- IV acyclovir is a vesicant. Concentration <7 mg/mL preferred for peripheral IV administration. Can also be infused through a midline catheter or PICC. If extravasation occurs, immediately stop infusion. Leave needle/cannula in place temporarily but do not flush the line. Gently aspirate extravasated solution; then remove needle/cannula. Elevate patient's extremity and apply dry warm compresses. Initiate hyaluronidase antidote for refractory cases in addition to supportive management. For hyaluronidase, inject a total of 1 mL (15 units/mL) intradermally or SUBQ as five separate 0.2-mL injections (using a tuberculin syringe) around the site of extravasation; if IV catheter remains in place, administer IV through the infiltrated catheter; may repeat in 30–60 min if no resolution.
- Do not administer acyclovir injectable topically, IM, SUBQ, PO, or in the eye.
Intermittent Infusion: Reconstitute 500-mg or 1-g vial with 10 mL or 20 mL, respectively, of sterile water for injection. Do not reconstitute with bacteriostatic water with benzyl alcohol or parabens. Shake well to dissolve completely. Diluent: Further dilute solution in 100 mL of D5W, 0.9% NaCl, dextrose/saline combinations, or LR. Concentration: 7 mg/mL. Patients requiring fluid restriction: 10 mg/mL. Use reconstituted solution within 12 hr. Once diluted for infusion, use solution within 24 hr. Refrigeration results in precipitation, which dissolves at room temperature.
Rate: Administer via infusion pump over 1 hr to minimize renal tubular damage.
Y-Site Compatibility:
- alemtuzumab
- allopurinol
- amikacin
- aminophylline
- amphotericin B deoxycholate
- amphotericin B liposomal
- ampicillin
- anidulafungin
- argatroban
- arsenic trioxide
- atracurium
- azithromycin
- bivalirudin
- bleomycin
- bumetanide
- buprenorphine
- busulfan
- butorphanol
- calcium chloride
- calcium gluconate
- carboplatin
- carmustine
- cefazolin
- cefotaxime
- cefotetan
- cefoxitin
- ceftaroline
- ceftazidime
- ceftriaxone
- cefuroxime
- cisplatin
- clindamycin
- cyclophosphamide
- cytarabine
- dactinomycin
- dantrolene
- defibrotide
- dexamethasone
- dexmedetomidine
- digoxin
- dimenhydrinate
- docetaxel
- doxorubicin liposomal
- doxycycline
- enalaprilat
- ephedrine
- ertapenem
- erythromycin
- etoposide
- etoposide phosphate
- famotidine
- fentanyl
- filgrastim
- fluconazole
- fluorouracil
- fosphenytoin
- furosemide
- glycopyrrolate
- heparin
- hydrocortisone
- hydromorphone
- ifosfamide
- imipenem/cilastatin
- insulin, regular
- isoproterenol
- leucovorin
- linezolid
- lorazepam
- magnesium sulfate
- mannitol
- melphalan
- methohexital
- methotrexate
- methylprednisolone
- metoprolol
- metronidazole
- milrinone
- mitoxantrone
- multivitamins
- nafcillin
- nitroglycerin
- octreotide
- oxacillin
- oxytocin
- paclitaxel
- pamidronate
- pemetrexed
- penicillin G potassium
- pentobarbital
- phenobarbital
- potassium acetate
- potassium chloride
- propofol
- propranolol
- remifentanil
- rituximab
- rocuronium
- sodium acetate
- sodium bicarbonate
- succinylcholine
- sufentanil
- theophylline
- thiotepa
- tigecycline
- tirofiban
- tobramycin
- trastuzumab
- trimethoprim/sulfamethoxazole
- vancomycin
- vasopressin
- vinblastine
- vincristine
- voriconazole
- zidovudine
- zoledronic acid
Y-Site Incompatibility:
- acetaminophen
- aminocaproic acid
- amiodarone
- ampicillin/sulbactam
- aztreonam
- cefepime
- chlorpromazine
- ciprofloxacin
- dacarbazine
- daptomycin
- daunorubicin
- dexrazoxane
- diazepam
- dobutamine
- dopamine
- doxorubicin hydrochloride
- epinephrine
- epirubicin
- eptifibatide
- esmolol
- fludarabine
- foscarnet
- gemcitabine
- gemtuzumab ozogamicin
- haloperidol
- hydralazine
- idarubicin
- irinotecan
- ketamine
- ketorolac
- labetalol
- levofloxacin
- lidocaine
- mesna
- methadone
- midazolam
- mitomycin
- mycophenolate
- nicardipine
- nitroprusside
- ondansetron
- palonosetron
- pentamidine
- phenylephrine
- phenytoin
- piperacillin/tazobactam
- potassium phosphates
- procainamide
- prochlorperazine
- promethazine
- sargramostim
- sodium phosphates
- tacrolimus
- topotecan
- vecuronium
- verapamil
- vinorelbine

Explain the purpose and side effects of acyclovir. Instruct patient to take medication as directed for the full course of therapy. Take missed doses as soon as possible but not just before next dose is due; do not double doses. Acyclovir should not be used more frequently or longer than prescribed. Advise patient to read Patient Information before starting and with each Rx refill in case of changes.
- Advise patients that the additional use of OTC creams, lotions, and ointments may delay healing and may cause spreading of lesions.
- Inform patient that acyclovir is not a cure; the virus lies dormant in the ganglia. Acyclovir will not prevent the spread of infection to others.
- Instruct patient to consult health care provider if symptoms are not relieved after 7 days of topical therapy or if oral acyclovir does not decrease the frequency and severity of recurrences. Immunocompromised patients may require a longer time, usually 2 wk, for crusting over of lesions.
- Instruct women with genital herpes to have yearly Papanicolaou smears because they may be more likely to develop cervical cancer.
Topical Instruct patient to apply ointment in sufficient quantity to cover all lesions every 3 hr, 6 times/day, for 7 days. A ½-inch ribbon of ointment covers approximately 4 square inches. Use a finger cot or glove when applying to prevent inoculation of other areas or spread to other people. Keep affected areas clean and dry. Loose-fitting clothing should be worn to prevent irritation.
- Avoid drug contact in or around eyes. Report any unexplained eye symptoms to health care provider immediately; ocular herpetic infection can lead to blindness.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding. Advise patient that condoms should be used during sexual contact and to avoid sexual contact while lesions are present.

Crusting over and healing of skin lesions.
Decrease in frequency and severity of recurrences.
Acceleration of complete healing and cessation of pain in herpes zoster.
Decrease in intensity of chickenpox.

Zovirax

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US Brand Names ⬆