Acyclovir Sodium

Name: Acyclovir Sodium

Uses for Acyclovir Sodium

Mucocutaneous, Ocular, and Systemic Herpes Simplex Virus (HSV) Infections

Treatment of initial and recurrent mucocutaneous HSV-1 and HSV-2 infections (e.g., orofacial, esophageal, genital, nasal, labial) in immunocompromised adults, adolescents, and children, including HIV-infected individuals.322 381 396 409 410 412 413 Drug of choice.322 381 396 410 412 413

Chronic suppressive or maintenance therapy (secondary prophylaxis) of recurrent HSV infections† in immunocompromised adults, adolescents, and children, including HIV-infected individuals who have frequent or severe recurrences.322 392 404 412

Treatment of orolabial HSV infections (including gingivostomatitis) in immunocompetent† adults and children;322 381 418 generally ineffective or minimally effective for prevention of recurrence of herpes labialis† in immunocompetent individuals.322 422

Treatment of eczema herpeticum† in patients with a history of atopic dermatitis.223 224

Treatment of HSV keratitis† in HIV-infected patients.407

Prophylaxis against recurrence of ocular HSV disease† in immunocompetent adults and children ≥12 years of age who had ocular HSV disease (blepharitis, conjunctivitis, epithelial keratitis, stromal keratitis, iritis) in one or both eyes within the preceding 12 months.408 419 Has been used for prophylaxis after penetrating keratoplasty for herpetic keratitis.420

Drug of choice for treatment of HSV encephalitis.211 212 246 248 322 381 395 409 410 412 413

Drug of choice for treatment of neonatal HSV infections, including mucocutaneous infections, infections involving skin, eyes, and mouth, and disseminated or CNS infections.244 322 324 353 356 381 395 408 409 410 413

Drug of choice for prevention of HSV recurrence† in hematopoietic stem cell transplant (HSCT) recipients seropositive for HSV; such prophylaxis not indicated in those seronegative for HSV.414

Genital Herpes

Treatment of initial episodes of genital herpes in adults and adolescents,206 207 208 244 305 313 322 381 403 409 including HIV-infected individuals.412

Treatment of first episodes of herpes proctitis†.305

Episodic treatment of recurrent episodes of genital herpes in adults and adolescents,244 313 322 381 403 including HIV-infected individuals.244 412

Chronic suppressive therapy of recurrent episodes of genital herpes in adults and adolescents,202 203 210 242 244 313 317 318 319 320 321 322 381 384 386 403 including HIV-infected individuals.244 412

CDC and others recommend oral acyclovir, oral famciclovir, or oral valacyclovir as drugs of choice for treatment of initial episodes of genital herpes and for episodic treatment or chronic suppressive therapy of recurrent genital herpes.244 313 381 412

Varicella-Zoster Infections

Treatment of varicella (chickenpox) in immunocompromised adults, adolescents, and children, including HIV-infected individuals.249 277 279 322 352 353 368 403 409 410 412 413 Drug of choice.249 277 279 322 352 353 368 410 412 413

Treatment of varicella (chickenpox) in immunocompetent adults, adolescents, and children.239 322 337 338 340 344 348 352 353 368 381 394 403 410 415 Varicella usually is a self-limited disease in otherwise healthy individuals and the role of acyclovir for treatment in these individuals is controversial;239 329 330 331 332 333 335 336 337 338 344 349 350 355 368 routine use not recommended by AAP and other clinicians.322 331 332 335 344 345 368

Treatment of herpes zoster (shingles, zoster) in immunocompetent261 284 285 309 353 or immunocompromised adults, adolescents, and children, including HIV-infected individuals.322 358 359 381 403 409 410 412 413 Drug of choice for serious or disseminated herpes zoster in immunocompromised patients.381 413

Treatment of herpes zoster ophthalmicus† in HIV-infected patients.407 412

Treatment of dermatomal herpes zoster in immunocompromised patients† including transplant recipients225 and HIV-infected patients.219 407 412

Alternative to varicella-zoster immune globulin (VZIG) for postexposure prophylaxis of VZV infection† in HSCT recipients.414 Although long-term prophylaxis not routinely recommended for prevention of recurrent VZV infections in HSCT recipients, such prophylaxis may be considered in those with severe, long-term immunodeficiency.414

Prevention of Cytomegalovirus (CMV) Disease in Transplant Recipients

Has been used for prevention of CMV disease† in solid organ transplant recipients354 360 363 364 365 366 367 398 399 414 and bone marrow transplant (BMT) recipients at risk for the disease; data regarding efficacy are conflicting.354 360 365 367 382

Has been used for prevention of CMV disease† in HSCT recipients; generally ineffective after autologous HSCT.414 Ganciclovir is drug of choice for prevention of CMV following autologous or allogeneic HSCT in adults, adolescents, and children.414

Not effective for prevention of CMV disease in HIV-infected individuals.404

Epstein-Barr Virus Infections and Disorders

Treatment of uncomplicated or complicated infectious mononucleosis, chronic infectious mononucleosis, and various disorders (e.g., oral hairy leukoplakia) associated with Epstein-Barr virus infections†;262 270 271 272 369 396 efficacy appears to be variable.230 262 272 273 274 275 276 369

Cautions for Acyclovir Sodium

Contraindications

  • Known hypersensitivity to acyclovir or valacyclovir.403 409

Warnings/Precautions

Warnings

Renal Effects

Increased BUN and/or Scr, anuria, and hematuria have been reported.403 409 Transient increases in BUN and/or Scr and decreases in Clcr reported in patients receiving IV acyclovir, particularly following rapid (over <10 minutes) IV infusion.409

Abnormal urinalysis (increase in formed elements in urine sediment) and pain or pressure on urination reported rarely with IV acyclovir.409

Renal failure, resulting in death, has occurred.341 403 409

Possible precipitation of acyclovir in renal tubules, resulting in renal tubular damage and acute renal failure, when the solubility of free acyclovir in the collecting duct is exceeded or following rapid IV administration.409

Risk of adverse renal effects during IV therapy depends on degree of hydration, urine output, concomitant therapy (i.e., nephrotoxic drugs), preexisting renal disease, and rate of administration (see Rate of Administration under Dosage and Administration).409

Alterations in renal function during IV acyclovir therapy can progress to acute renal failure but generally are transient and resolve spontaneously or following improved hydration and electrolyte balance, dosage adjustment, or discontinuance of the drug.409

Hematologic Effects

Potentially fatal thrombotic thrombocytopenic purpura/hemolytic uremic syndrome reported in immunocompromised patients receiving acyclovir.403 409

General Precautions

Nervous System Effects

Possible encephalopathic effects (e.g., lethargy, obtundation, tremors, confusion, hallucinations, agitation, seizures, coma) in patients receiving IV acyclovir.409

Use with caution in patients with underlying neurologic abnormalities and in those with serious renal, hepatic, or electrolyte abnormalities or substantial hypoxia.409

Local Effects

Severe local inflammatory reactions, including tissue necrosis, have occurred following infusion of acyclovir into extravascular tissues.409

Sodium Content

Sodium salt of acyclovir contains 4.2 mEq of sodium per gram of acyclovir.409

Specific Populations

Pregnancy

Category B.403 409

CDC, AAP, and others state that oral acyclovir may be used during pregnancy to treat first episodes or severe recurrent episodes of genital herpes244 322 381 412 421 and IV acyclovir may be used during pregnancy to treat severe HSV infection (especially life-threatening disseminated infections).244 322 412 421 CDC and others also recommend acyclovir for treatment of varicella during pregnancy,412 415 particularly during the second and third trimesters.415

Lactation

Distributed into milk following oral or IV administration.251 308 403 409 421 Use with caution.403 409

Women with active herpetic lesions near or on the breast should refrain from breast-feeding.322

Pediatric Use

Safety and efficacy of oral acyclovir not established in children <2 years of age.403

Geriatric Use

For treatment of herpes zoster (shingles, zoster), no substantial differences in efficacy of oral acyclovir relative to younger adults, but duration of pain after healing may be longer in geriatric patients.403

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently to IV acyclovir than younger adults.409

Select dosage with caution because of age-related decreases in renal function and potential for concomitant disease and drug therapy.409 Consider monitoring renal function.409

Possible increased incidence of adverse CNS effects (coma, confusion, hallucinations, somnolence), GI effects (nausea, vomiting), or dizziness during oral acyclovir therapy compared with younger adults.403

Hepatic Impairment

Use with caution.a

Renal Impairment

Decreased acyclovir clearance.409 Increased risk of adverse renal and encephalopathic effects.409

Adjust dosage to prevent drug accumulation, decrease risk of toxicity, and maintain adequate plasma drug concentrations.316 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

With oral therapy, nausea and/or vomiting and diarrhea.403 With IV therapy, local reactions at the injection site (inflammation, phlebitis).409

Interactions for Acyclovir Sodium

Nephrotoxic Agents

Potential pharmacodynamic interaction (increased risk of renal dysfunction and/or reversible CNS manifestations); use concomitantly with caution.403 409

Specific Drugs

Drug

Interaction

Comments

Interferon

Additive or synergistic antiviral effect against HSV-1 in vitroa

Clinical importance unknown;a use with caution409

Methotrexate

Manufacturer states that IV acyclovir should be used with caution in patients receiving intrathecal methotrexate409

Probenecid

Decreased renal clearance of acyclovir403 409

Zidovudine

Neurotoxicity (profound drowsiness, lethargy) reported in at least 1 patient298

Monitor patients closely during concomitant therapy298

Stability

Storage

Oral

Capsules and Tablets

Tight, light-resistant containers at 15–25°C.403

Suspension

15–25°C.403

Parenteral

Powder for IV Infusion

15–25°C.409 Use reconstituted solution within 12 hours.409 Refrigeration of this solution may cause a precipitate, which will redissolve at room temperature.409 Following dilution with infusion solution, use drug within 24 hours.409

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

Bacteriostatic water for injection containing parabens should not be used to reconstitute acyclovir sodium powder; precipitation may occur.424

When diluted with >10% dextrose, a yellow discoloration may appear but does not affect potency.a

Compatible424

Dextrose 5% and sodium chloride 0.2, 0.45, or 0.9%

Dextrose 5%

Lactated Ringer’s

Sodium chloride 0.9%

Drug Compatibility Admixture Compatibility424

Compatible

Fluconazole

Incompatible

Dobutamine HCl

Dopamine HCl

Variable

Meropenem

Y-site Injection Compatibility424

Compatible

Allopurinol sodium

Amikacin sulfate

Amphotericin B cholesteryl sulfate complex

Ampicillin sodium

Cefamandole nafate

Cefazolin sodium

Cefoperazone sodium

Cefotaxime sodium

Cefoxitin sodium

Ceftazidime

Ceftizoxime sodium

Ceftriaxone sodium

Cefuroxime sodium

Chloramphenicol sodium succinate

Cimetidine HCl

Clindamycin phosphate

Dexamethasone sodium phosphate

Dimenhydrinate

Diphenhydramine HCl

Docetaxel

Doxorubicin HCl liposome injection

Doxycycline hyclate

Erythromycin lactobionate

Etoposide phosphate

Famotidine

Filgrastim

Fluconazole

Gatifloxacin

Gentamicin sulfate

Granisetron HCl

Heparin sodium

Hydrocortisone sodium succinate

Hydromorphone HCl

Imipenem–cilastatin sodium

Linezolid

Lorazepam

Magnesium sulfate

Melphalan HCl

Methylprednisolone sodium succinate

Metoclopramide HCl

Metronidazole

Milrinone lactate

Multivitamins

Nafcillin sodium

Oxacillin sodium

Paclitaxel

Penicillin G potassium

Pentobarbital sodium

Perphenazine

Piperacillin sodium

Potassium chloride

Propofol

Ranitidine HCl

Remifentanil HCl

Sodium bicarbonate

Tacrolimus

Teniposide

Theophylline

Thiotepa

Ticarcillin disodium

Tobramycin sulfate

Trimethoprim–sulfamethoxazole

Vancomycin HCl

Zidovudine

Incompatible

Amifostine

Amsacrine

Aztreonam

Cefepime HCl

Dobutamine HCl

Dopamine HCl

Fludarabine phosphate

Foscarnet sodium

Gemcitabine HCl

Idarubicin HCl

Levofloxacin

Ondansetron HCl

Piperacillin sodium–tazobactam sodium

Sargramostim

Tacrolimus

Vinorelbine tartrate

Variable

Cisatracurium besylate

Diltiazem HCl

Meperidine HCl

Meropenem

Morphine sulfate

Advice to Patients

  • Advise patients that acyclovir is not a cure for genital herpes and there are no data evaluating whether acyclovir prevents transmission of genital herpes to others.244

  • Importance of avoiding sexual contact with uninfected partners when genital lesions or prodromal symptoms are present, since there is a risk of infecting sexual partners.244 Genital herpes can be transmitted in the absence of symptoms.244

  • Importance of initiating treatment as soon as possible following onset of signs and symptoms.403 409

  • Advise patients receiving chronic suppressive therapy of the need for periodic reassessment of the continued need for acyclovir therapy.244 403

  • Importance of not exceeding the recommended dosage and duration of therapy.409

  • Importance of maintaining adequate hydration during treatment.403 409

  • Importance of contacting clinician if severe or troublesome adverse effects occur.403

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs.403 409

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.403

  • Importance of advising patients of other important precautionary information. (See Cautions.)

(web3)