Zovirax Cream

Medical Editor: John P. Cunha, DO, FACOEP Last updated on RxList: 7/20/2022

Drug Summary

What Is Zovirax Cream?

Zovirax (acyclovir) Cream, 5% is a herpes simplex virus (HSV) nucleoside analogue DNA polymerase inhibitor used to treat recurrent herpes labialis (cold sores) in immunocompetent adults and adolescents 12 years of age and older.

What Are Side Effects of Zovirax Cream?

Common side effects of Zovirax Cream include:

  • application site reactions such as dry lips,
  • skin sloughing,
  • skin dryness,
  • cracked lips,
  • burning skin,
  • itching,
  • flakiness of skin,
  • contact dermatitis,
  • skin swelling, and
  • temporary burning or stinging on skin where the medication is applied.

Seek medical care or call 911 at once if you have the following serious side effects:

  • Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
  • Serious heart symptoms such as fast, irregular, or pounding heartbeats; fluttering in your chest; shortness of breath; and sudden dizziness, lightheartedness, or passing out;
  • Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors.

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

Dosage for Zovirax Cream

Zovirax Cream should be applied five times per day for four days. Therapy should be initiated as early as possible following the onset of signs or symptoms of herpes labialis i.e., during the prodrome or when lesions appear.

What Drugs, Substances, or Supplements Interact with Zovirax Cream?

Zovirax may interact with other drugs. Tell your doctor all medications and supplements you use.

Zovirax Cream During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Zovirax Cream. It is unknown if topically applied acyclovir passes into breast milk. Oral forms of this drug pass into breast milk. Do not nurse if you have lesions on or near the breasts. Consult your doctor before breastfeeding.

Additional Information

Our Zovirax (acyclovir) Cream, 5% Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

Drug Description


ZOVIRAX is the brand name for acyclovir, a synthetic nucleoside analogue active against herpes viruses. ZOVIRAX Cream, 5% is a formulation for topical administration.

The chemical name of acyclovir is 2-amino-1,9-dihydro-9-[(2-hydroxyethoxy)methyl]-6H-purin-6-one; it has the following structural formula:

ZOVIRAX® (acyclovir) Structural Formula Illustration

Acyclovir is a white, crystalline powder with the molecular formula C8H11N5O3 and a molecular weight of 225. The maximum solubility in water at 37°C is 2.5 mg/mL. The pKa's of acyclovir are 2.27 and 9.25.

Each gram of ZOVIRAX Cream, 5% contains 50 mg of acyclovir and the following inactive ingredients: cetostearyl alcohol, mineral oil, poloxamer 407, propylene glycol, sodium lauryl sulfate, water, and white petrolatum.

Indications & Dosage


BLUDIGO is indicated for use as a visualization aid in the cystoscopic assessment of the integrity of the ureters in adults following urological and gynecological open, robotic, or endoscopic surgical procedures.


Recommended Dosage

The recommended dose of BLUDIGO is 5 mL given as an intravenous injection over 1 minute.

The blue color is detectable at the ureteral orifices within 4 minutes to 9 minutes after the intravenous injection.

Important Administration Instructions

  • Monitor blood pressure and cardiac rhythm during and following the injection [see WARNINGS AND PRECAUTIONS].
  • Use immediately after opening ampule.
  • Withdraw the contents of the ampule through a 5 micron or smaller filter straw/filter needle to ensure that the withdrawn solution contains no particulates. The withdrawn solution should be inspected visually for particulate matter and discoloration prior to administration.
  • Do not administer with infusion assemblies used with other diluents or drugs.
  • Discard any unused portion.


Dosage Forms And Strengths

Injection: 40 mg/5 mL (8 mg/mL) indigotindisulfonate sodium as a dark blue solution in a single-dose amber glass ampule.

BLUDIGO (indigotindisulfonate sodium injection, USP) 40 mg/5 mL (8 mg/mL) is a dark blue solution supplied in a carton of 5 single-dose amber glass ampules (NDC 81284-315-05).

Storage And Handling

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Store in original carton to protect from light. Do not refrigerate or freeze.

Use immediately after opening ampule. Discard unused portion.

Manufactured for: PROVEPHARM SAS 22 rue Marc Donadille 13013 Marseille, FRANCE. Manufactured by: CENEXI 52 rue Marcel et Jacques Gaucher 94120 Fontenay sous Bois, FRANCE. Distributed by: PROVEPHARM INC. 100 Springhouse Drive, Suite 105 Collegeville, PA 19426, USA. Revised: Jul 2022

Side Effects & Drug Interactions


Clinically significant adverse reactions are described elsewhere in the labeling:

  • Cardiovascular Reactions [see WARNINGS AND PRECAUTIONS]
  • Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of BLUDIGO was evaluated in a randomized, intra-patient controlled, blind to dose of BLUDIGO, clinical trial. A total of 118 adult patients undergoing endoscopic urological or gynecological procedures were treated intravenously; 58 (49%) of these patients received one dose of BLUDIGO 2.5 mL and 60 (51%) of patients received one dose of BLUDIGO 5 mL. The 2.5 mL dose is not approved [see DOSAGE AND ADMINISTRATION]. The mean age of patients was 51 years and 35 (30%) patients were 65 years of age or older. The majority of patients were White 105 (89%) and female 87 (74%).

The adverse reactions (≥1%) reported in the clinical trial are provided in Table 1.

Table 1: Adverse Reactions Reported at ≥ 1% of Patients Receiving BLUDIGO 5 mL Intravenously

(N=60) n (%)
Constipation 3 (5.0)
Nausea 2 (3.3)
Vomiting 2 (3.3)
Abdominal Pain 2 (3.3)
Pyrexia 2 (3.3)
ALT increase 2 (3.3)
Dysuria 1 (1.7)

Postmarketing Experience

The following adverse reactions have been identified following the use of indigotindisulfonate sodium injection products. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiovascular disorders: cardiac arrest, arrhythmia, asystole, atrioventricular block second degree, hypotension, elevation in blood pressure, bradycardia, tachycardia

General disorders and administration site conditions: injection site discoloration

Immune system disorders: anaphylactic reactions with hypotension, dyspnea, bronchospasm, urticaria, erythema


No Information provided

Warnings & Precautions


Included as part of the PRECAUTIONS section.


Cardiovascular Reactions

Severe or life-threatening cardiovascular reactions including cardiac arrest, arrhythmia, asystole, second degree atrioventricular block, hypotension, elevation in blood pressure, bradycardia, and tachycardia have been reported generally within 60 minutes following administration of indigotindisulfonate sodium injection products and required urgent intervention [see ADVERSE REACTIONS].

Indigotindisulfonate may cause vasoconstriction by interference with vasodilation mediated by nitric oxide dependent mechanisms and by direct vasoconstriction. Indigotindisulfonate may also cause hypotension. Patients with hypertension, heart rate and conduction disorders, or medications causing bradycardia may be at increased risk for elevated blood pressure, hypotension, and bradycardia.

Closely monitor blood pressure and cardiac rhythm during and following the injection of BLUDIGO. Interrupt administration if reactions are observed.

Hypersensitivity Reactions

Serious anaphylactic reactions with hypotension, dyspnea, bronchospasm, urticaria, or erythema have been reported with the use of indigotindisulfonate sodium injection products [see ADVERSE REACTIONS]. BLUDIGO is contraindicated in patients with known hypersensitivity to indigotindisulfonate [see CONTRAINDICATIONS]. Monitor patients for anaphylactic reactions and have emergency equipment and trained personnel readily available.

Interference With Oximetry Measurements

Indigotindisulfonate has been reported to interfere with light absorption and transiently interfere with pulse oximetric methods. Anesthesiologists should be aware of the potential for artifactual reduction in SpO2 when anesthetized patients are administered BLUDIGO.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility


Carcinogenicity studies in animals have not been conducted with indigotindisulfonate sodium using the intravenous route of administration.

Long-term studies in mice with oral and subcutaneous administration of indigotindisulfonate sodium revealed no carcinogenic effects.


Although indigotindisulfonate sodium has been evaluated in a number of Ames assay studies, an Ames assay study that follows all currently recommended guidelines has not been performed. Indigotindisulfonate was not genotoxic in all those Ames assays. The mutagenicity of indigotindisulfonate was inconclusive in the in vitro mouse L5187Y Lymphoma TK +/-assay. Orally administered indigotindisulfonate was not mutagenic in the in vivo mouse micronucleus test. An in vivo micronucleus test with indigotindisulfonate sodium using the intravenous route of administration has not been conducted.


Fertility studies with indigotindisulfonate sodium using the intravenous route of administration have not been conducted.

Use In Specific Populations


Risk Summary

Available data from case reports, case series, observational studies and clinical experience with indigotindisulfonate sodium injection use in pregnant women over several decades have not identified a drug associated risk of adverse maternal and fetal adverse effects. Indigotindisulfonate sodium injection use during the first trimester of pregnancy is rare; thus, the data are insufficient to evaluate for a drug associated risk of major birth defects and miscarriage. The majority of the published data were from intra-amniotic injections. Animal reproduction studies using the intravenous route of administration have not been conducted. Oral administration of indigotindisulfonate sodium to pregnant rats and rabbits produced no evidence of fetal harm. However, oral availability is low (3%) so that the risk of intravenous administration of indigotindisulfonate sodium during pregnancy cannot be evaluated from the data available.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.


Risk Summary

It is not known if indigotindisulfonate is present in animal or human milk. The transfer of indigotindisulfonate into breastmilk is likely to be low and adverse effects on the breastfed infant are not expected [see CLINICAL PHARMACOLOGY]. There are no data on the effect of indigotindisulfonate on the breastfed infant or milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for BLUDIGO and any potential adverse effects on the breastfed infant from BLUDIGO or from the underlying maternal condition.

Pediatric Use

The safety and effectiveness of BLUDIGO have not been established in pediatric patients.

Geriatric Use

Of the total number of subjects in the clinical study of BLUDIGO, 23 (20%) were 65 to 74 years of age, and 12 (10%) were 75 and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Renal Impairment

Indigotindisulfonate is known to be excreted by the kidney through tubular secretion. No dedicated pharmacokinetic study using BLUDIGO in patients with varying degree of renal impairment has been conducted. Based on subgroup analyses in the randomized clinical trial, dose adjustment is not needed in patients with mild to moderate renal impairment (estimated glomerular filtration rate (eGFR) 30 to 89 mL/min derived from the Modification of Diet in Renal Disease formula).

BLUDIGO has not been studied in patients with eGFR < 30 mL/min and is not recommended for use in these patients.

Overdose & Contraindications


No Information provided


BLUDIGO is contraindicated in patients with known hypersensitivity to indigotindisulfonate or any of its components [see WARNINGS AND PRECAUTIONS].

Clinical Pharmacology


Mechanism Of Action

Indigotindisulfonate is a dye excreted by the kidney through tubular secretion and enhances visualization of the ureteral orifices by its deep blue color.


The blue color is detectable at the ureteral orifices within 4 minutes to 9 minutes after the intravenous injection.


The pharmacokinetic properties of BLUDIGO are presented in Table 2.

Table 2: Pharmacokinetics of Indigotindisulfonate in Healthy Adults Following Intravenous Administration of BLUDIGO 5 mL (40 mg)

5 mL (40 mg)
General Information
Cmax (CV%), pg/mL 6.33 (58.4)
AUC0-inf (CV%), pgh/mL 1.15 (36.4)
Mean (CV%) Volume of Distribution, L 10.7 (36.1)
Protein Binding, in vitro About 90%
Mean (CV%) Elimination Half-life, minutes 12 (34.1)
Mean (CV%) Clearance, Urinary 7.08 (66.3)
L/hour Total 40.2 (45.1)
Primary Metabolic Pathways Oxidative metabolism
Urine (CV%)a 16.0% (44.0)
Feces <2%
aUnchanged drug
Cmax= maximum plasma concentration; AUC0-INF=area under the plasma concentration-time curve from time of administration extrapolated to infinity; CV=coefficient of variation

Clinical Studies

The safety and efficacy of BLUDIGO were evaluated in a randomized intra-patient controlled, blind to dose of BLUDIGO, multi-center study (NCT04228445) in 118 adult patients undergoing endoscopic urological or gynecological surgical procedures including cystoscopic (58%), robotic (28%), and transvaginal (14%) approaches.

The majority of patients were white (89%), female (74%), and younger than 65 years of age (70%). Mean age was 51 years, and age ranged from 20 to 88 years.

Patients were randomized in a 1:1 ratio to receive 2.5 mL or 5 mL of BLUDIGO intravenously prior to the end of the surgical procedure. Each patient underwent cystoscopy and received 5 mL of sodium chloride injection 0.9% followed by the randomized BLUDIGO dose for visualization of urinary flow from the ureteral orifices. The 2.5 mL dose is not approved [see DOSAGE AND ADMINISTRATION].

The ureteral orifices and urine flow were observed and video recorded from 0 to 10 minutes post injection, with separate recordings made following sodium chloride injection and BLUDIGO. The conspicuity of the urine flow from the ureteral orifices was assessed in a randomized, blinded fashion by two independent central reviewers using a 5-point scale (1 = no urine flow observed; 2 = weak urine flow, little color contrast; 3 = Color contrast or significant urine flow; 4 = strong urine flow with good color contrast; and 5 = strong urine flow with striking contrast in color) once after sodium chloride injection and twice after BLUDIGO resulting in paired data. The surgeons also reviewed and scored conspicuity of the urine flow from the ureteral orifices.

The responder for a ureter is defined as the difference in conspicuity score between BLUDIGO and sodium chloride injection being at least one point difference and the conspicuity score following BLUDIGO alone being greater than or equal to three. The reviewer agreement with the responder endpoint is acceptable. The proportion of responders along with its 95% confidence interval by ureter and reviewer or surgeon is summarized in Table 3.

Table 3: Summary of Proportion of Responders by Ureter and Reviewer or Surgeon in Patients Receiving BLUDIGO 5 mL

Left Ureter
Right Ureter
Reviewer 1
% Responder* 63% 76%
95% CL** (48%, 77%) (61%, 87%)
Reviewer 2
% responder 78% 82%
95% CL (63%, 88%) (68%, 91%)
% responder 71% 82%
95% CL (57%, 83%) (68%, 91%)
*responder: IC conspicuity score ≥ 3 and difference (IC – Saline) in conspicuity score ≥1, missing data is imputed as non-responder
** two-sided 95% confidence limits for the proportion of responder, calculated using the Clopper-Pearson (Exact) method

Medication Guide


Cardiovascular Reactions

Advise the patient of the possibility of developing elevated blood pressure, hypotension, bradycardia, tachycardia, or atrioventricular block during or after the administration of BLUDIGO [see WARNINGS AND PRECAUTIONS].

Injection Site And Urine Discoloration

Inform the patient that BLUDIGO may cause a blue discoloration of injection site and urine and that the discoloration should resolve within 48 hours. Advise the patient to inform the healthcare provider if the discoloration of the injection site is associated with other symptoms [see ADVERSE REACTIONS].

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