Vistide

Generic Name: Cidofovir
Class: Nucleosides and Nucleotides
VA Class: AM800
Chemical Name: (S)-[[2-(4-amino-2-oxo-1(2H)-pyrimidinyl)-1-(hydroxymethyl)ethoxy]methyl]phosphonic acid dihydrate
Molecular Formula: C₈H₁₄N₃O₆P•2H₂O
CAS Number: 149394-66-1

• Nephrotoxicity


• 
  

  The major toxicity is renal impairment.¹ Acute renal failure resulting in dialysis and/or contributing to death has occurred with as few as 1 or 2 doses of cidofovir.¹

  
  


• 
  

  To reduce risk of nephrotoxicity, IV prehydration with 0.9% sodium chloride prior to each cidofovir dose and concomitant probenecid must be used.¹ (See Hydration and see Concomitant Probenecid under Dosage and Administration.) Renal function (serum creatinine and urine protein) must be monitored within 48 hours prior to each dose and dosage modified as appropriate based on any changes in renal function.¹

  
  


• 
  

  Cidofovir is contraindicated in patients receiving other nephrotoxic drugs.¹

  
  

• Neutropenia


• 
  

  Neutropenia has been observed in association with cidofovir; neutrophil counts should be closely monitored during treatment.¹

  
  

• Other Warnings


• 
  

  The only FDA-approved indication is treatment of cytomegalovirus (CMV) retinitis in HIV-infected patients.¹

  
  


• 
  

  In animal studies, cidofovir was carcinogenic, teratogenic, and caused hypospermia.¹

  
  

Introduction

Antiviral; purine nucleotide analog of cytosine.^{3 5 7 10 11 12 13 14 15 18 21 24}

Uses for Vistide

Cytomegalovirus (CMV) Infections

Treatment of cytomegalovirus (CMV) retinitis in HIV-infected adults or adolescents†.^{1 21 24 25 31 52 69} Cidofovir is not curative; stabilization or improvement of ocular manifestations may occur, but progression of retinitis is possible during or following treatment.^{1 3 17 21 23 24 25 31}

Drugs of choice for initial induction and maintenance therapy of CMV retinitis are IV ganciclovir, IV ganciclovir in conjunction with oral valganciclovir, IV foscarnet, IV cidofovir, oral valganciclovir, or intravitreal fomivirsen.^{37 52 69}

Alternative to IV ganciclovir or IV foscarnet for long-term suppressive or maintenance therapy (secondary prophylaxis) of recurrent CMV disease† in HIV-infected adults or adolescents†.^{38 69}

Safety and efficacy not established for treatment of other CMV infections (e.g., pneumonitis, gastroenteritis), congenital or neonatal CMV disease, or CMV disease in individuals not infected with HIV.¹

Mucocutaneous Herpes Simplex Virus (HSV) Infections

Treatment of acyclovir-resistant herpes simplex virus (HSV-1 and HSV-2) infections† in immunocompromised patients, including HIV-infected adults or adolescents†.^{39 40 42 43 69} A drug of choice.^{38 69}

Alternative for chronic suppressive or maintenance therapy (secondary prophylaxis) against recurrence of HSV† in HIV-infected adults and adolescents† who have frequent or severe recurrence.^{38 69} Drugs of choice for secondary prophylaxis are oral acyclovir, oral famciclovir, or oral valacyclovir; IV cidofovir and IV foscarnet are alternatives for such prophylaxis if acyclovir-resistant HSV are suspected.^{38 69}

Has been used topically† for treatment of mucocutaneous HSV infections† or genital herpes† caused by acyclovir-resistant strains.^{40 43 61 69}

Smallpox

Suggested for use in treatment of smallpox†.^{49 50 51} No clinical data to date; possible benefits remain to be determined.^{49 50 51}

Alternative for treatment of certain serious complications of smallpox vaccination†, including progressive vaccinia, eczema vaccinatum, generalized vaccinia (if severe or with underlying illness), and inadvertent inoculation (if severe because of large numbers of lesions, toxicity, or pain).^{62 63} Safety and efficacy have not been determined and possible benefits remain to be determined.^{62 63}

Vaccinia immune globulin (VIG) usually recommended for management of complications of smallpox vaccination; cidofovir is available from CDC under an investigational new drug (IND) protocol for patients who fail to respond to VIG and for patients who are near death and will also be available if all inventories of VIG have been exhausted.^{62 63}

Monkeypox

Suggested for use in treatment of severe human monkeypox†.⁶⁵ Efficacy has not been established, but drug is active in vitro against monkeypox and has in vivo activity in animal models.^{53 65 66 67 68} Not indicated for prophylaxis of monkeypox.⁶⁵ Clinical consultation on use of cidofovir for treatment of severe monkeypox infection can be obtained from state health departments or CDC (877-554-4625).⁶⁵

Vistide Dosage and Administration

General

Hydration

• 
  

  To minimize risk of nephrotoxicity, patients must receive adequate IV prehydration with 0.9% sodium chloride prior to each cidofovir dose.¹

  
  


• 
  

  Patients should receive ≥1 L of 0.9% sodium chloride infused IV over 1–2 hours immediately before each cidofovir infusion.¹

  
  


• 
  

  For patients who can tolerate additional fluid, an additional 1 L of 0.9% sodium chloride should be administered; this second saline infusion should be initiated either concomitantly with or immediately after the cidofovir infusion and should be administered over 1–3 hours.¹

  
  


• 
  

  Volume repletion and maintenance are particularly important in patients with potential volume depletion secondary to conditions such as chronic diarrhea, poor fluid intake, or HIV-related wasting.²⁹

  
  

Concomitant Probenecid

• 
  

  In addition to adequate hydration, all patients must receive a regimen of concomitant oral probenecid.^{1 3 7 30 32} Cidofovir undergoes renal tubular secretion, suggesting that use of probenecid may reduce the risk of renal toxicity of cidofovir by decreasing its concentration within proximal tubular cells.^{1 4 7}

  
  


• 
  

  Because concomitant use of probenecid is considered necessary, cidofovir is contraindicated in patients who cannot receive probenecid (e.g., those with a history of severe hypersensitivity to probenecid or other sulfonamide derivatives).^{1 30}

  
  


• 
  

  The recommended dosage of probenecid to be administered concomitantly with cidofovir is 2 g orally 3 hours prior to initiation of the cidofovir infusion, followed by 1-g doses orally 2 and 8 hours after completion of the cidofovir infusion, for a total probenecid dose of 4 g.^{1 2 18}

  
  


• 
  

  To reduce risk of nausea and/or vomiting associated with probenecid, food can be ingested prior to each probenecid dose and concomitant administration of an effective antiemetic can be considered.¹

  
  


• 
  

  For patients who develop allergic or other hypersensitivity manifestations with probenecid, appropriate prophylactic or therapeutic use of antihistamines and/or acetaminophen should be considered.¹

  
  


• 
  

  Because probenecid can affect the pharmacokinetics of many drugs, a careful assessment should be made of other drugs that the patient may be receiving.¹ Although patients receiving antiretroviral therapy can continue to receive the drugs during cidofovir therapy,¹ consider possible interactions between probenecid and antiretrovirals (e.g., zidovudine).^{1 18} (See Specific Drugs under Interactions.)

  
  

Administration

Administer by IV infusion.¹

Has been administered by intravitreal injection†,^{6 20 24 25 26} but a preparation for intravitreal administration is not commercially available in the US.^{1 30} Direct intraocular injection of the IV preparation (even if diluted) is contraindicated since such administration has been associated with iritis, ocular hypotony (clinically important decreases in intraocular pressure [IOP]), and permanent visual impairment.^{1 30}

Has been administered topically as an extemporaneously prepared gel containing cidofovir 1%†.^{40 43 61 69}

IV Infusion

To minimize the risk of nephrotoxicity, patients must receive adequate IV prehydration with 0.9% sodium chloride prior to each cidofovir dose and also should receive concomitant oral probenecid.¹ (See Hydration and see Concomitant Probenecid under Dosage and Administration.)

Exercise caution should be exercised in preparing, administering, and discarding solutions of cidofovir according to guidelines for handling mutagenic substances.^{1 30} If cidofovir concentrate or a diluted solution of the drug comes in contact with the skin or mucosa, the affected area should be washed immediately and thoroughly with soap and water.¹ Partially used vials of cidofovir and diluted solutions should be discarded by high temperature incineration.¹

Dilution

For IV infusion, cidofovir concentrate must be diluted in 100 mL of 0.9% sodium chloride injection in a compatible infusion container (e.g., PVC, glass, ethylene/propylene copolymer).¹

Compatibility with Ringer’s, lactated Ringer’s, or bacteriostatic infusion solutions has not been established.¹

Rate of Administration

IV infusions should be given over 1 hour at a constant rate via a controlled-infusion device (e.g., pump).¹ To minimize risk of nephrotoxicity, the IV dose must not be infused over a shorter period.^{1 29}

Dosage

Available as cidofovir dihydrate; dosage is expressed in terms of anhydrous drug.¹

Pediatric Patients

Cytomegalovirus (CMV) Infections

CMV Retinitis in HIV-infected Adolescents†

IV

Initial induction therapy: 5 mg/kg once weekly for 2 consecutive weeks.⁶⁹

Maintenance therapy: 5 mg/kg once every 2 weeks (i.e., every other week).⁶⁹

Prevention of Recurrence (Secondary Prophylaxis) of CMV Disease in HIV-infected Adolescents†

IV

5 mg/kg once every other week.^{38 69} Initiate secondary prophylaxis after initial induction treatment.^{38 69}

Consideration can be given to discontinuing secondary CMV prophylaxis in adolescents with sustained (e.g., for ≥6 months) increase in CD4⁺ T-cell counts to >100–150/mm³ in response to potent antiretroviral therapy.^{38 69}

This decision should be made in consultation with an ophthalmologist and factors such as the magnitude and duration of CD4⁺ T-cell increase, anatomic location of the retinal lesion, vision in the contralateral eye, and feasibility of regular ophthalmic monitoring should be considered.^{38 69}

Relapse of CMV retinitis could occur following discontinuance of secondary prophylaxis, especially in those whose CD4⁺ T-cell count decreases to <50/mm³; relapse has been reported rarely in those with CD4⁺ T-cell counts >100/mm³.^{38 69}

Reinitiate secondary CMV prophylaxis if CD4⁺ T-cell count decreases to <100–150/mm³.^{38 69}

Herpes Simplex Virus (HSV) Infections†

Acyclovir-resistant HSV Infections in immunocompromised Adolescents†

IV

5 mg/kg once weekly for 2–4 weeks until a response is obtained.^{39 40 69}

Acyclovir-resistant Genital Herpes†

Topical

Apply extemporaneously prepared gel containing cidofovir 1%† to affected area once daily for 5 days.^{43 61}

Adults

Cytomegalovirus (CMV) Infections

CMV Retinitis in HIV-infected Adults

IV

Initial induction therapy: 5 mg/kg once weekly for 2 consecutive weeks.^{1 21 24 30 31 52 69}

Maintenance therapy: 5 mg/kg once every 2 weeks (i.e., every other week).^{1 24 52 69}

Prevention of Recurrence (Secondary Prophylaxis) of CMV Disease in HIV-infected Adults†

IV

5 mg/kg once every other week.^{38 69} Initiate secondary prophylaxis after initial induction treatment.^{38 69}

Consideration can be given to discontinuing secondary CMV prophylaxis in adults with sustained (e.g., for ≥6 months) increase in CD4⁺ T-cell counts to >100–150/mm³ in response to potent antiretroviral therapy.^{38 69}

This decision should be made in consultation with an ophthalmologist and factors such as the magnitude and duration of CD4⁺ T-cell increase, anatomic location of the retinal lesion, vision in the contralateral eye, and feasibility of regular ophthalmic monitoring should be considered.^{38 69}

Relapse of CMV retinitis could occur following discontinuance of secondary prophylaxis, especially in those whose CD4⁺ T-cell count decreases to <50/mm³; relapse has been reported rarely in those with CD4⁺ T-cell counts >100/mm³.^{38 69}

Reinitiate secondary CMV prophylaxis if CD4⁺ T-cell count decreases to <100–150/mm³.^{38 69}

Herpes Simplex Virus (HSV) Infections†

Acyclovir-resistant HSV Infections in immunocompromised Adults†

IV

5 mg/kg once weekly for 2–4 weeks until a response is obtained.^{39 40 69}

Acylcovir-resistant Genital Herpes†

Topical

Apply extemporaneously prepared gel containing cidofovir 1%† to affected area once daily for 5 days.^{43 61}

Smallpox†

Smallpox Vaccination Complications†

IV

CDC has proposed a cidofovir dosage of 5 mg/kg administered once as an IV infusion over 1 hour.⁶³ If there is no response to the initial dose, administration of a second dose 1 week later can be considered.⁶³ If a second dose is needed, cidofovir dosage may need to be adjusted if renal function has deteriorated.⁶³

Information on dosage and administration of cidofovir and IND materials will be provided by CDC if the drug is released for treatment of certain serious complications of smallpox vaccination†.^{58 63}

Monkeypox†

IV

No specific dosage recommendations available.⁶⁵ Information on appropriate dosage for severe monkeypox infection should be obtained as part of clinical consultation services provided by state health departments or CDC (877-554-4625).⁶⁵

Special Populations

Renal Impairment

Contraindicated in patients with serum creatinine >1.5 mg/dL, calculated Cl_cr ≤55 mL/minute, or urine protein ≥100 mg/dL (equivalent to 2+ or greater).¹

If serum creatinine increases by 0.5 mg/dL or more above baseline or urinary proteinuria of 3+ or greater develops, cidofovir must be discontinued.^{1 29 30}

Patients who develop 2+ proteinuria in the face of a stable serum creatinine during cidofovir therapy should be observed carefully (including close monitoring of serum creatinine and urinary protein) to detect potential deterioration that would warrant dose reduction or temporary discontinuance of the drug.^{29 30}

Cytomegalovirus (CMV) Infections

CMV Retinitis in HIV-infected Adults

IV

If clinically important decreases in renal function (e.g., increase in serum creatinine to 0.3–0.4 mg/dL above baseline) occur in patients receiving cidofovir, maintenance dosage must be reduced to 3 mg/kg administered IV at the usual rate and frequency.^{1 29 52} Some clinicians suggest a cidofovir dosage of 2.5–4 mg/kg administered IV at the usual rate and frequency in HIV-infected patients with a Cl_cr 50–80 mL/minute.⁴¹

Geriatric Patients

Select dosage with caution because of age-related decreases in renal function.¹ (See Renal Impairment under Dosage and Administration.)

Cautions for Vistide

Contraindications

• 
  

  Hypersensitivity to cidofovir.¹

  
  


• 
  

  Serum creatinine >1.5 mg/dL, calculated Cl_cr ≤55 mL/minute, or urine protein ≥100 mg/dL (equivalent to 2+ or greater).¹

  
  


• 
  

  Concomitant administration of other nephrotoxic drugs.¹

  
  


• 
  

  History of severe hypersensitivity to probenecid or other sulfonamide derivatives.^{1 30}

  
  


• 
  

  Direct intraocular injection of the IV preparation.^{1 30}

  
  

Warnings/Precautions

Warnings

Nephrotoxicity

Dose-dependent nephrotoxicity is the major dose-limiting toxicity.¹ Acute renal failure, resulting in dialysis and/or contributing to death, has occurred with as few as 1 or 2 doses.^{1 29 35} Most cases were associated with risk factors for nephrotoxicity, such as preexisting mild renal insufficiency.²⁹

Renal function (serum creatinine and urine protein) must be monitored within 48 hours prior to each cidofovir dose and dosage modified as appropriate based on any changes in renal function.¹

Proteinuria may be an early sign of cidofovir-induced nephrotoxicity.¹ IV hydration should be performed and the test repeated to confirm.¹

If renal function deteriorates, consider dosage reduction or discontinuance of the drug should.^{1 29} Continued cidofovir may lead to additional proximal tubular cell injury, which may result in glycosuria; decreases in serum phosphate, uric acid, and bicarbonate concentrations; increases in serum creatinine concentrations; and/or acute renal failure, occasionally requiring dialysis.¹

Occasionally, renal function may not return to baseline following discontinuance of cidofovir.¹

Franconi's syndrome can occur.

Hematologic Effects

Neutropenia (≤500/mm³) has occurred.¹ WBC count and differential should be monitored prior to each cidofovir dose.^{1 30}

Ocular Effects

Uveitis or iritis reported.¹ Decreased IOP and severe hypotony reported.¹ Risk of ocular hypotony may be increased in patients with preexisting diabetes mellitus.¹

Periodically monitor IOP, visual acuity, and ocular symptoms during therapy.^{1 35 36}

If anterior uveitis develops, treatment with appropriate agents (topical corticosteroids with or without cycloplegic therapy) may be indicated.³⁵

Metabolic Acidosis

Decreased serum bicarbonate associated with proximal tubule injury and renal wasting syndrome (including Fanconi's syndrome) has occurred.¹

Metabolic acidosis in association with liver dysfunction and pancreatitis has resulted in death.¹

General Precautions

Carcinogenic and Mutagenic Potential

Cidofovir should be considered a potential carcinogen in humans.¹ Has caused tumors (principally mammary adenocarcinomas) in rats.¹

Effects on Fertility

In animals, cidofovir has caused reduced testes weight and hypospermia.¹ Possibility exists that such changes could occur in humans and cause infertility.¹

Contraceptive Precautions

Women of childbearing potential should use effective contraception during and for 1 month following cidofovir treatment.¹

Men should practice barrier contraceptive methods during and for 3 months after cidofovir treatment.¹

Specific Populations

Pregnancy

Category C.¹ (See Contraceptive Precautions under Cautions.)

Lactation

Not known whether distributed into milk.¹ Discontinue nursing or the drug.¹

Pediatric Use

Safety and efficacy not established in children <18 years of age.^{1 30}

Because of the risk of potential long-term carcinogenic and reproductive toxicity, use with extreme caution in children and only when potential benefits outweigh risks.¹

Geriatric Use

Safety and efficacy have not been evaluated in adults >60 years of age.¹

Dosage should be adjusted in response to any change in renal function that may occur during therapy.¹ Because geriatric patients frequently have reduced GFR, particular attention should be paid to monitoring renal function prior to and during cidofovir therapy in this age group.¹ (See Renal Impairment under Dosage and Administration.)

Renal Impairment

Contraindicated in patients with preexisting renal impairment, including serum creatinine >1.5 mg/dL, calculated Cl_cr ≤55 mL/minute, or urine protein ≥100 mg/dL (equivalent to 2+ or greater).¹ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Nephrotoxicity; neutropenia; ocular effects (decreased intraocular pressure/ocular hypotony, anterior uveitis/iritis); metabolic acidosis.¹

Interactions for Vistide

Nephrotoxic Drugs

Concomitant use of other nephrotoxic drugs (e.g., aminoglycosides, amphotericin B, foscarnet, IV pentamidine, vancomycin, nonsteroidal anti-inflammatory agents) is contraindicated since it may result in increased risk of nephrotoxicity.¹ Other nephrotoxic agents should be discontinued ≥7 days prior to initiating cidofovir.¹

Specific Drugs

Drug	Interaction	Comments
Probenecid	Decreased renal clearance of cidofovir1	Used to therapeutic advantage to minimize risk of cidofovir-associated nephrotoxicity1
Zidovudine	No evidence of pharmacokinetic interactions with cidofovir;1 concomitant probenecid (used to reduce risk of cidofovir-associated nephrotoxicity) can increase zidovudine concentrations1	Temporarily discontinue zidovudine or decrease zidovudine dosage by 50% during cidofovir and concomitant probenecid therapy1

Vistide Pharmacokinetics

Absorption

Bioavailability

Low concentrations of cidofovir are absorbed systemically following topical application of extemporaneously prepared gel containing cidofovir 1%† to mucocutaneous HSV lesions.⁴³

Distribution

Extent

Undetectable concentrations in CSF following IV administration.¹

Not known whether distributed into milk.¹

Plasma Protein Binding

<6%.¹

Elimination

Metabolism

Cidofovir is converted via cellular enzymes to the pharmacologically active diphosphate metabolite.^{1 2 3 5 7 11 12 13 15 16 18 24}

Elimination Route

When administered with the usual concomitant probenecid regimen, 70–85% of an IV cidofovir dose is eliminated unchanged in urine within 24 hours.¹ If administered without probenecid, 80–100% of the IV cidofovir dose is eliminated unchanged in urine within 24 hours.¹

Removed by hemodialysis.¹

Stability

Storage

Parenteral

Concentrate for IV Infusion

20–25°C.¹

Diluted solutions of cidofovir should be administered within 24 hours of preparation.¹

If diluted solutions are prepared in advance, they may be refrigerated at 2–8°C but should be administered within 24 hours of preparation;^{1 30} the solutions should be allowed to reach room temperature before administration.¹

Compatibility

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

Parenteral

Compatibility with Ringer’s, lactated Ringer’s, or bacteriostatic infusion fluids has not been established.¹

Solution Compatibility^a

Compatible
Dextrose 5% in sodium chloride 0.45%
Dextrose 5% in water
Sodium chloride 0.9%

Actions and SpectrumActions

• 
  

  Cidofovir is converted via cellular enzymes to the pharmacologically active diphosphate metabolite, which has in vitro and in vivo antiviral activity.^{1 2 3 5 7 11 12 13 15 16 18 24}

  
  


• 
  

  Cidofovir diphosphate interferes with viral DNA synthesis and inhibits viral replication^{10 11 12 13 25} by competitive inhibition of viral DNA polymerase^{6 14 16} and incorporation and termination of the growing viral DNA chain.^{1 3} The inhibitory activity of cidofovir diphosphate is highly selective^{1 9 10 11 12 20} because of its greater affinity for viral DNA polymerases⁵ than for human DNA polymerases.^{1 3}

  
  


• 
  

  Active against various Herpesviridae, including cytomegalovirus (CMV), herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus (VZV), and Epstein-Barr virus (EBV).^{1 3 16 24 33} Also active in vitro against adenovirus,^{3 16 24} human papillomavirus (HPV),^{3 24 33} and human polyomavirus.^{1 2 3 7 11 13 15 16 18 24 30 34}

  
  


• 
  

  Has in vitro activity against poxviruses, including vaccinia virus (cowpox), monkeypox, and variola virus (the causative agent of smallpox).^{45 46 47 53 57 65 67 68} Also has in vivo activity against monkeypox in animal models^{53 65 66 67 68} and against vaccinia virus in mice.^{47 48 53 54 55 56}

  
  


• 
  

  May be active against some ganciclovir-resistant CMV^{2 9 27} and some acyclovir-resistant HSV.^{2 18}

  
  


• 
  

  CMV resistant to cidofovir can be selected in vitro.¹

  
  

Advice to Patients

• 
  

  Advise patients that cidofovir is not a cure for CMV retinitis; they may continue to experience progression of retinitis during or following treatment.¹ Regular ophthalmologic examinations are necessary.¹

  
  


• 
  

  Advise HIV-infected patients receiving zidovudine to temporarily discontinue zidovudine or decrease the zidovudine dose by 50% on days cidofovir is administered.¹

  
  


• 
  

  The major toxicity of cidofovir is renal impairment; dosage adjustments or discontinuance may be required.¹ Importance of closely monitoring renal function (routine urinalysis, serum creatinine) during cidofovir therapy.¹

  
  


• 
  

  Importance of maintaining adequate hydration and taking concomitant probenecid to minimize risk of renal impairment.¹

  
  


• 
  

  Advise patients that cidofovir causes tumors (principally mammary adenocarcinomas) in animals and should be considered a potential carcinogen in humans.¹

  
  


• 
  

  Advise women that only limited numbers of women were enrolled in clinical trials evaluating cidofovir.¹

  
  


• 
  

  Advise patients that cidofovir caused reduced testes weight and hypospermia in animals; such changes may occur in humans and cause infertility.¹

  
  


• 
  

  Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs.¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

  
  


• 
  

  Advise women of childbearing potential to use effective contraception during and for 1 month after cidofovir therapy. Men should be advised to practice barrier contraceptive methods during and for 3 months after cidofovir treatment.¹

  
  


• 
  

  Importance of advising patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

For treatment of smallpox vaccine complications†, cidofovir will be distributed through the Strategic National Stockpile (formerly National Pharmaceutical Stockpile [NPS]).⁶² Clinicians should contact CDC Smallpox Vaccine Adverse Events Clinical Information Line at 877-554-4625 to coordinate shipment from NPS.⁶² Cidofovir should be expected to arrive within 12 hours of approval for release.⁶²

Cidofovir

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection, concentrate, for IV infusion only	75 mg (of anhydrous cidofovir) per mL	Vistide	Gilead

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Vistide 75MG/ML Solution (GILEAD SCIENCES): 5/$855.94 or 15/$2397.6

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions July 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Gilead Sciences. Vistide (cidofovir) injection prescribing information. Foster City, CA; 2000 Sept.

2. Flaherty JF. Current and experimental therapeutic options for cytomegalovirus disease. Am J Health-Syst Pharm. 1996; 53(Suppl 2):S4-11.

3. Hitchcock MJM, Jaffe HS, Martin JC et al. Cidofovir, a new agent with potent anti-herpesvirus activity. Antivir Chem Chemother. 1996; 7:115-27.

4. Cundy KC, Petty BG, Flaherty J et al. Clinical pharmacokinetics of cidofovir in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother. 1995; 39:1247- 52. [IDIS 348683] [PubMed 7574510]

5. Cherrington JM, Miner R, Hitchcock MJM et al. Susceptibility of human cytomegalovirus to cidofovir is unchanged after limited in vivo exposure to various clinical regimens of drug. J Infect Dis. 1996; 173:987-92. [IDIS 362104] [PubMed 8603981]

6. Kirsch LS, Arevalo JF, Chavez de la Paz E et al. Intravitreal cidofovir (HPMPC) treatment of cytomegalovirus retinitis in patients with acquired immune deficiency syndrome. Ophthalmology. 1995; 102:533-43. [IDIS 345783] [PubMed 7724170]

7. Polis MA, Spooner KM, Baird BF et al. Anticytomegaloviral activity and safety of cidofovir in patients with human immunodeficiency virus infection and cytomegalovirus viruria. Antimicrob Agents Chemother. 1995; 39:882-6. [IDIS 345410] [PubMed 7785989]

8. Minckler D. Intravitreal cidofovir (HPMPC) treatment of cytomegalovirus retinitis in patients with acquired immune deficiency syndrome. Ophthalmology. 1995; 253:702.

9. Flores-Aguilar M, Huang J-S, Wiley CA et al. Long-acting therapy of viral retinitis with (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine. J Infect Dis. 1994; 169:642-7. [PubMed 8158041]

10. Neyts J, Snoeck R, Schols D et al. Selective inhibition of human cytomegalovirus DNA synthesis by (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine [(S)-HPMPC] and 9-(1,3- dihydroxy-2-propoxymethyl)guanine (DHPG). Virology. 1990; 179:41-50. [PubMed 2171213]

11. Neyts J, Snoeck R, Balzarini J et al. Particular characteristics of the anti-human cytomegalovirus activity of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) in vitro. Antivir Res. 1991; 16:41-52. [PubMed 1663729]

12. Snoeck R, Sakuma T, De Clercq E et al. (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine, a potent and selective inhibitor of human cytomegalovirus replication. Antimicrob Agents Chemother. 1988; 32:1839-44. [PubMed 2854454]

13. Bronson JJ, Ghazzouli I, Hitchcock MJM et al. Synthesis and antiviral activity of the nucleotide analogue (S)-1-[3-hydroxy-2-(phosphonylmethoxy) propyl]cytosine. J Med Chem. 1989; 32:1457-63. [PubMed 2544723]

14. De Castro LM, Kern ER, De Clercq E et al. Phosphonylmethoxyalkyl purine and pyrimidine derivatives for the treatment of opportunistic cytomegalovirus and herpes simplex virus infections in murine AIDS. Antivir Res. 1991; 16:101-14. [PubMed 1663726]

15. De Clercq E, Sakuma T, Baba M et al. Antiviral activity of phosphonylmethoxyalkyl derivatives of purine and pyrimidines. Antivir Res. 1987; 8:261-72. [PubMed 3451698]

16. Ho H-T, Woods KL, Bronson JJ et al. Intracellular metabolism of the antiherpes agent (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine. Mol Pharmacol. 1991; 41:197- 202.

17. Polis MA, Masur H. Promising new treatments for cytomegalovirus retinitis. JAMA. 1995; 273:1457-59. [IDIS 346437] [PubMed 7723160]

18. Lalezari JP, Drew WL, Glutzer E et al. (S)-1-[3-hydroxy-2- (phosphonylmethoxy)propyl]cytosine (cidofovir): results of a phase I/II study of a novel antiviral nucleotide analogue. J Infect Dis. 1995; 171:788-96. [IDIS 346945] [PubMed 7706804]

20. Kirsch LS, Arevalo JF, De Clercq E et al. Phase I/II study of intravitreal cidofovir for the treatment of cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome. Am J Ophthalmol. 1995; 119:466-76. [IDIS 345787] [PubMed 7709971]

21. Lalezari J, Stagg R, Kuppermann B et al. A phase II/III randomized study of immediate versus deferred intravenous (IV) cidofovir (CDV, HPMPC) for AIDS patients with peripheral CMV retinitis (CMV-R). Paper presented at International Conference on Ocular Infections. Jerusalem, Israel: 1995 June 18.

23. Lalezari J, Holland G, Stagg R et al. A randomized, controlled study of cidofovir (CDV) for relapsing cytomegalovirus retinitis (CMV-R) in patients with AIDS. Proceedings of ICAAC San Francisco 1995.

24. National Institutes of Health. Conference: advances in the management of AIDS- related cytomegalovirus retinitis. Ann Intern Med. 1996; 125:126-36. [IDIS 367652] [PubMed 8678367]

25. Jabs DA. Treatment of cytomegalovirus retinitis in patients with AIDS. Ann Intern Med. 1996; 125:144-5. [IDIS 367654] [PubMed 8678370]

26. Rahhal FM, Arevalo JF, Chavez de la Paz E et al. Treatment of cytomegalovirus retinitis with intravitreous cidofovir in patients with AIDS. Ann Intern Med. 1996; 125:98-103. [IDIS 367650] [PubMed 8678386]

27. Cantrill HL. Intravitreal cidofovir (HPMPC) treatment of cytomegalovirus retinitis in patients with acquired immune deficiency syndrome. Ophthalmology. 1995; 102:542.

28. Yuan LC, Samuels GJ, Visor GC. Stability of cidof

Erythromycin

Class: Erythromycins
VA Class: AM200
CAS Number: 114-07-8
Brands: E.E.S., ERYC, EryPed, Ery-Tab, Erythrocin, Eryzole, PCE, Pediazole

Introduction

Antibacterial; macrolide antibiotic produced by Saccharopolyspora erythraeus.^{263 268 f}

Uses for Erythromycin

Acute Otitis Media (AOM)

Treatment of AOM in children caused by susceptible Haemophilus influenzae.²⁶⁴ The fixed-combination preparation containing erythromycin ethylsuccinate and sulfisoxazole acetyl must be used;²⁶⁴ erythromycin is not effective when used alone for treatment of H. influenzae infections.^{264 c}

The fixed-combination preparation containing erythromycin ethylsuccinate and sulfisoxazole acetyl is an alternative (not a preferred agent) for treatment of AOM.^{311 483} The drug is recommended as an alternative in patients with type I penicillin hypersensitivity.³¹¹ May not be effective for treatment of AOM that fails to respond to amoxicillin since a high incidence of S. pneumoniae resistant to the fixed-combination drug has been reported.⁴⁸³

Pharyngitis and Tonsillitis

Treatment of pharyngitis and tonsillitis caused by S. pyogenes (group A β-hemolytic streptococci).^{242 262 263 268 311 392 441 472 f} Generally effective in eradicating S. pyogenes from the nasopharynx, but efficacy in prevention of subsequent rheumatic fever has not been established to date.^a

CDC, AAP, IDSA, AHA, and others recommend oral penicillin V or IM penicillin G benzathine as treatments of choice;^{243 311 392 441 472} oral cephalosporins and oral macrolides considered alternatives.^{311 392 441 472} Amoxicillin sometimes used instead of penicillin V, especially for young children.⁴⁴¹

Erythromycin usually the preferred alternative for treatment of streptococcal pharyngitis in patients hypersensitive to penicillin.^{243 311 392 441} Although S. pyogenes resistant to erythromycin and other macrolides have been reported and may be prevalent in some areas of the world (e.g., Japan, Finland), the incidence of these resistant S. pyogenes in the US has been relatively low to date.^{311 392 441 446}

Respiratory Tract Infections

Treatment of respiratory tract infections caused by susceptible S. pneumoniae.^{263 268 f 268 269 270 f}

Treatment of respiratory tract infections caused by Mycoplasma pneumoniae or C. pneumoniae.^{263 268 f 268 a c f}

Erythromycin usually not effective when used alone for treatment of respiratory tract infections caused by H. influenzae.^{242 262 269 c f}

Skin and Skin StructureInfections

Treatment of mild to moderate skin and skin structure infections caused by S. pyogenes or Staphylococcus aureus.^{263 268 f 268 a b c f} Consider that erythromycin-resistant Staphylococci may develop during treatment.^{263 268 f a b c f}

Treatment of erythrasma caused by Corynbacterium minutissimum.^{263 268 f 268 b c f}

Acne

Treatment of acne†.⁴⁵⁹

Amebiasis

Has been used for treatment of intestinal amebiasis caused by Entamoeba histolytica.^{242 262 263 268 f} Erythromycin generally not recommended for treatment of amebiasis; regimen of choice for intestinal amebiasis is metronidazole or tinidazole followed by a luminal amebicide such as iodoquinol or paromomycin.^{259 311}

Anthrax

Alternative for treatment of anthrax†.^{218 227 472}

Multiple-drug parenteral regimens recommended for treatment of inhalational anthrax that occurs as the result of exposure to B. anthracis spores in the context of biologic warfare or bioterrorism.^{216 347} Initiate treatment with IV ciprofloxacin or doxycycline and 1 or 2 other anti-infective agents predicted to be effective (e.g., chloramphenicol, clindamycin, rifampin, vancomycin, clarithromycin, imipenem, penicillin, ampicillin);^{216 347} if meningitis is established or suspected, use IV ciprofloxacin (rather than doxycycline) and chloramphenicol, rifampin, or penicillin.²¹⁶

Bartonella Infections

Has been used in conjunction with IM or IV ceftriaxone for treatment of bacteremia caused by Bartonella quintana† (formerly Rochalimaea quintana).⁴⁶⁰

Optimum regimens for treatment of infections caused by B. quintana or for treatment of cat scratch disease or other B. henselae infections have not been identified.^{460 462 463}

USPHS/IDSA suggests that long-term suppression with erythromycin or doxycycline be considered to prevent recurrence of Bartonella infection in HIV-infected patients†.⁴²⁰

Campylobacter Infections

Treatment of symptomatic enteric infections caused by Campylobacter jejuni†. Recommended by CDC,²⁷² IDSA,²⁷¹ and AAP³¹¹ as a treatment of choice.

Chancroid

Treatment of chancroid† (genital ulcers caused by H. ducreyi).^{228 248 472}

CDC and others recommend azithromycin, ceftriaxone, ciprofloxacin or erythromycin as drugs of choice for treatment of chancroid.^{228 248 472} HIV-infected patients and uncircumcised patients may not respond to treatment as well as those who are HIV-negative or circumcised.^{228 248 472} Some experts prefer the 7-day erythromycin regimen instead of single-dose azithromycin or ceftriaxone regimens in HIV-infected individuals.²²⁸

Chlamydial Infections

Alternative for treatment of uncomplicated urethral, endocervical, or rectal infections caused by Chlamydia trachomatis when tetracyclines and azithromycin are contraindicated or not tolerated.^{228 248 f} Erythromycin is less effective than either azithromycin or doxycycline and GI effects associated with the drug may discourage patient compliance with the regimen;²²⁸ CDC recommends that the first dose be taken under supervision.²²⁸

A drug of choice for treatment of urogenital chlamydial infections in pregnant women and in young children.²²⁸

Alternative for presumptive treatment of coexisting chlamydial infections in patients receiving treatment for gonorrhea.^{228 311} Preferred drugs are azithromycin or doxycycline;²²⁸ erythromycin may be preferred in young children.³¹¹

Treatment of urethritis caused by Ureaplasma urealyticum.^f

Treatment of chlamydial pneumonia in infants.^{f 248}

Treatment of initial episodes and recurrences of chlamydial conjunctivitis in neonates.^{228 248 311 f}

Alternative to doxycycline for treatment of lymphogranuloma venereum† caused by invasive serotypes of C. trachomatis (serovars L1, L2, L3).^{228 248 311} Erythromycin may be the preferred regimen for pregnant and lactating women.²²⁸

Alternative for treatment of psittacosis when tetracyclines are contraindicated (e.g., in pregnant women, children younger than 9 years of age).^{311 451}

Diphtheria

Adjunct to diphtheria antitoxin for treatment of diphtheria caused by Corynebacterium diphtheria.^{261 263 268 311 454 455 474 c f} Diphtheria antitoxin is the most important aspect of treatment of respiratory diphtheria.^{261 311 454 455} Anti-infectives may eliminate C. diphtheriae from infected sites, prevent spread of the organism and further toxin production, and prevent or terminate the diphtheria carrier state, but appear to be of no value in neutralizing diphtheria toxin and should not be considered a substitute for antitoxin therapy.^{311 454 455}

Because diphtheria infection often does not confer immunity, active immunization with a diphtheria toxoid preparation should be initiated or completed during convalescence.^{311 455}

Prevention of diphtheria in close contacts of patients with diphtheria.^{261 263 311 455} Prophylaxis is indicated in all household or other close contacts of individuals with suspected or proven diphtheria, regardless of vaccination status; prophylaxis should be initiated promptly and should not be delayed pending culture results.^{311 454 455} An age-appropriate diphtheria toxoid preparation also may be necessary depending on immunization status.^{261 311}

Elimination of diphtheria carrier state in individuals known to carry toxigenic strains of C. diphtheriae.^{261 311 454 455}

Granuloma Inguinale (Donovanosis)

Alternative for treatment of granuloma inguinale† (donovanosis) caused by Calymmatobacterium granulomatis.^{228 450}

CDC recommends doxycycline or co-trimoxazole as drugs of choice; ciprofloxacin, erythromycin, and azithromycin are alternatives.²²⁸ Erythromycin may be preferred in pregnant and lactating women.²²⁸

Legionnaires’ Disease

Treatment of Legionnaires’ disease caused by Legionella pneumophila; used with or without rifampin.^{242 262 263 268 270 311 452 453 472 c f}

Lyme Disease

Alternative for treatment of early Lyme disease†.^{214 310 311 394 395 397 399 472 473 476 477 478} IDSA, AAP, and others recommend doxycycline, amoxicillin, or cefuroxime as first-line agents; macrolides may be less effective.^{214 265 267 274 331 472 475}

Nongonococcal Urethritis

Treatment of nongonococcal urethritis (NGU).^{228 242 248 262 263}

CDC and others recommend azithromycin or doxycycline as drugs of choice for treatment of NGU;^{228 248} erythromycin (erythromycin base or ethylsuccinate) or fluoroquinolones (levofloxacin, ofloxacin) are alternatives.^{228 248} A regimen of erythromycin and metronidazole is recommended by CDC for treatment of recurrent and persistent urethritis in patients who were compliant with their initial regimen and have not been re-exposed.²²⁸

Pelvic Inflammatory Disease (PID)

IV erythromycin lactobionate followed by oral erythromycin has been used for treatment of PID) caused by N. gonorrhoeae,^{242 262 263 c f} but erythromycins are not included in current CDC recommendations for treatment of PID.²²⁸

Pertussis

Treatment of Bordetella pertussis infection (pertussis, whooping cough);^{268 253 261 311 455 457 472 f} a drug of choice.^{253 261 311 455 457 472}

Prevention of pertussis in contacts of patients with the disease;^{253 261 268 311 455 457 472 f} drug of choice.^{253 261 311 455 457 472}

CDC, AAP, and other clinicians recommend anti-infective prophylaxis for all household and other close contacts (e.g., those in childcare) of individuals with pertussis, regardless of age or vaccination status.^{261 311 455 456} Close contacts <7 years of age who are not fully immunized against pertussis also should receive the remaining required doses of a preparation containing pertussis vaccine (using minimal intervals between doses) and those who are fully immunized but have not received a vaccine dose within the last 3 years should receive a booster dose of a pertussis vaccine preparation.²⁶¹

Syphilis

Has been used as an alternative for treatment of primary syphilis in penicillin-allergic individuals.^{262 263 268 f}

Penicillin G is drug of choice for treatment of all stages of syphilis.^{228 248} Erythromycin is less effective than other possible penicillin alternatives²⁷⁵ and is not included in CDC recommendations for treatment of any form of syphilis in adults or adolescents (including primary, secondary, latent, or tertiary syphilis or neurosyphilis).²²⁸

Preoperative Intestinal Antisepsis

Adjunct to mechanical cleansing of the large intestine for intestinal antisepsis prior to elective colorectal surgery; used in conjunction with neomycin.^{237 262}

Prevention of Bacterial Endocarditis

Has been used as an alternative to penicillins for prevention of bacterial endocarditis in penicillin-allergic patients undergoing certain dental, oral, respiratory tract, or esophageal procedures who have cardiac conditions that put them at high or moderate risk.³⁰² AHA no longer recommends erythromycin for this use, but states that practitioners who have successfully used an erythromycin (i.e., erythromycin ethylsuccinate, erythromycin stearate) for prophylaxis in individual patients may choose to continue using these agents.⁴³⁶

Erythromycins are not appropriate for prevention of bacterial endocarditis in patients undergoing GI, biliary, or genitourinary tract procedures because causative organisms are likely to be erythromycin-resistant.⁴³⁶

Consult most recent AHA recommendations for specific information on which cardiac conditions are associated with high or moderate risk of endocarditis and which procedures require prophylaxis.⁴³⁶

Prevention of Rheumatic Fever Recurrence

Alternative to IM penicillin G benzathine, oral penicillin V potassium, and oral sulfadiazine for prevention of recurrence of rheumatic fever (secondary prophylaxis) in patients hypersensitive to penicillins and sulfonamides.^{311 392 c f}

Continuous prophylaxis recommended following treatment of documented rheumatic fever (even if manifested solely by Sydenham chorea) and in those with evidence of rheumatic heart disease.^{311 392}

Prevention of Perinatal Group B Streptococcal Disease

Alternative to penicillin G or ampicillin for prevention of perinatal group B streptococcal (GBS) disease† in penicillin-allergic pregnant women at risk for anaphylaxis with a β-lactam anti-infective.^{246 311 415}

Intrapartum anti-infective prophylaxis to prevent early-onset neonatal GBS disease is administered to women identified as GBS carriers during routine prenatal GBS screening performed at 35–37 weeks during the current pregnancy and to women who have GBS bacteriuria during the current pregnancy, a previous infant with invasive GBS disease, unknown GBS status with delivery at <37 weeks gestation, amniotic membrane rupture for ≥18 hours, or intrapartum temperature of ≥38°C.^{246 415}

Penicillin G is the regimen of choice and ampicillin is the preferred alternative.^{246 415} Cefazolin can be used in penicillin-allergic women who do not have immediate-type penicillin hypersensitivity, but clindamycin or erythromycin should be used in penicillin-allergic women at high risk for anaphylaxis.⁴¹⁵

Consider that S. agalactiae (group B streptococci) with in vitro resistance to clindamycin and erythromycin has been reported with increasing frequency;⁴¹⁵ perform in vitro susceptibility tests of clinical isolates obtained during GBS prenatal screening.⁴¹⁵ GBS resistant to erythromycin often are resistant to clindamycin, although this may not be evident in results of in vitro testing.⁴¹⁵ If in vitro susceptibility testing is not possible, results are unknown, or isolates are found to be resistant to erythromycin or clindamycin, vancomycin is recommended for intrapartum prophylaxis in penicillin-allergic women at high risk for anaphylaxis with β-lactams.⁴¹⁵

Erythromycin Dosage and Administration

Administration

Administer orally as erythromycin base, stearate, ethylsuccinate, or estolate.^a Administer erythromycin lactobionate by IV infusion.^c

Oral route usually preferred and should replace parenteral route as soon as possible.^a

Oral Administration

Erthromycin delayed-release tablets (PCE Dispertab, Ery-Tab) may be given without regard to meals,^{262 b} but optimal absorption of PCE Dispertab occurs when the tablets are given in the fasting state (at least 30 minutes and, preferably, 2 hours before meals).^b Erythromycin film-coated tablets should be administered in the fasting state (at least 30 minutes and, preferably, 2 hours before or after meals).^{d e}

Erythromycin delayed-release capsules containing enteric-coated pellets of erythromycin (ERYC) may be swallowed intact or the entire contents of a capsule(s) may be sprinkled on a small amount of applesauce immediately prior to administration; subdividing the contents of a capsule is not recommended.^h The enteric-coated pellets contained in the capsules should not be chewed or crushed.^h If the capsule contents are administered by sprinkling on applesauce, the patient should drink some water after swallowing the applesauce to ensure that the pellets are swallowed.^h If the pellets are accidentally spilled, the dose preparation should be started over with a new capsule.^h

Erythromycin ethylsuccinate oral suspensions,^{268 f} chewable tablets,^f and film-coated tablets^{268 f} (E.E.S., EryPed) are given without regard to meals. Chewable tablets should not be swallowed whole.^f

Erythromycin stearate preferably should be administered in the fasting state or immediately before a meal.²⁶³

Fixed-combination preparation containing erythromycin ethylsuccinate and sulfisoxazole acetyl is given without regard to meals.²⁶⁴

Reconstitution

Reconstitute erythromycin ethylsuccinate powders for oral suspension with water according to manufacturers' directions.^{268 f}

IV Infusion

Administer erythromycin lactobionate by continuous or intermittent IV infusion.^c Do not administer by rapid or direct IV injection because of the local irritative effects of the drug.^c

Continuous IV infusion usually is preferred, but the drug may be administered by intermittent IV infusion every 6 hours.^c

Reconstitution

Reconstitute ADD-Vantage vials according to the manufacturer's instructions using 0.9% sodium chloride or 5% dextrose injection.^c The ADD-Vantage vials are for single use only.^c

Rate of Administration

For intermittent IV infusion; one-fourth of the total daily dose is administered over 20–60 minutes at intervals no longer than every 6 hours.^c

Dosage

Available as erythromycin base, estolate, ethylsuccinate, stearate, or lactobionate; dosage expressed in terms of erythromycin.^a Dosage of the fixed-combination preparation containing erythromycin ethylsuccinate and sulfisoxazole acetyl is expressed in terms of the erythromycin or sulfisoxazole content.²⁶⁴

Erythromycin ethylsuccinate has different absorption characteristics than other commercially available forms of oral erythromycin and higher doses of the ethylsuccinate may be needed to achieve therapeutic effects.^{268 f} For adults, 400 mg of erythromycin as the ethylsuccinate provides erythromycin activity similar to that provided by 250 mg of erythromycin as the base, estolate, or stearate.^{268 f}

Pediatric Patients

General Pediatric Dosage

Treatment of Infections

Oral

Erythromycin (base, estolate, ethylsuccinate, or stearate): 30–50 mg/kg daily in 2–4 equally divided doses.^{242 262 263 268 311 b d e f i}

Dosage may be doubled for severe infections.^{242 262 268 311 b d e f}

IV

Erythromycin (lactobionate): 15–20 mg/kg daily.^c Dosage up to 4 g daily may be used for severe infections.^c

Acute Otitis Media (AOM)

Oral

Children ≥2 months of age (fixed combination containing erythromycin ethylsuccinate and sulfisoxazole acetyl): 12.5 mg/kg (based on erythromycin content) every 6 hours or 17 mg/kg (based on erythromycin content) every 8 hours (up to 2 g daily).²⁶⁴ Alternatively, the following approximate dosages expressed in terms of volumes of the fixed-combination suspension can be used.²⁶⁴ (See Table 1 and Table 2.)

Pediazole Dosage (6-Hour Dosing) for AOM in Children ≥2 Months of Age

Weight (in kg)	Dose (repeated every 6 h for 10 days)
<8	Calculate dose by body weight
8–15.9	2.5 mL
16–23.9	5 mL
24–31.9	7.5 mL
>32	10 mL

Pediazole Dosage (8-Hour Dosing) for AOM in Children ≥2 Months of Age

Weight (in kg)	Dose (repeated every 8 h for 10 days)
<6	Calculate dose by body weight
6–11.9	2.5 mL
12–17.9	5 mL
18–23.9	7.5 mL
24–30	10 mL
>30	12.5 mL

Amebiasis

Entamoeba histolytica Infections

Oral

Erythromycin (base, estolate, ethylsuccinate, or stearate): 30–50 mg/kg daily in divided doses for 10–14 days.^{242 262 268 d e f}

Anthrax†

IV

Erythromycin (lactobionate): 20–40 mg/kg daily given in divided doses every 6 hours.²¹⁸

Must be used in multiple-drug regimens that initially include IV ciprofloxacin or IV doxycycline and 1 or 2 other anti-infectives predicted to be effective.^{216 347}

Duration of treatment is 60 days if anthrax occurred as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism.^{216 347}

Chlamydial Infections

Uncomplicated Urethral, Endocervical, or Rectal Infections in Children Weighing <45 kg

Oral

Erythromycin (base or ethylsuccinate): 50 mg/kg daily (maximum 2 g daily) given in 4 divided doses for 14 days.²²⁸

Uncomplicated Urethral, Endocervical, or Rectal Infections in Adolescents

Oral

Erythromycin (base or stearate): 500 mg 4 times daily for 7 days.^{228 242 248 262 311 d e} Alternatively, 666 mg every 8 hours for 7 days.^{242 262}

Erythromycin (ethylsuccinate): 800 mg 4 times daily for 7 days.²²⁸

Presumptive Treatment of Chlamydial Infections in Children Weighing <45 kg with Gonorrhea

Oral

Erythromycin (base or ethylsuccinate): 50 mg/kg daily (maximum 2 g daily) given in 4 divided doses for 7 days.^{228 311}

Presumptive Treatment of Chlamydial Infections in Adolescents with Gonorrhea

Oral

Erythromycin (base): 500 mg 4 times daily for 7 days.²²⁸

Erythromycin (ethylsuccinate): 800 mg 4 times daily for 7 days.²²⁸

Treatment of Pneumonia Caused by C. trachomatis

Oral

Erythromycin (base, ethylsuccinate, or stearate): 50 mg/kg daily given in 4 divided doses for ≥14 days.^{228 248 262 263 311} Follow-up is recommended and a second course of therapy may be necessary.^{228 311}

Treatment of Ophthalmia Neonatorum Caused by C. trachomatis

Oral

Erythromycin (base, ethylsuccinate, or stearate): 50 mg/kg daily given in 4 divided doses for 14 days.^{228 248 263 311} Follow-up is recommended and a second course of therapy may be necessary.^{228 311}

Diphtheria

Treatment of Diphtheria

Oral

Erythromycin: 40–50 mg/kg daily (maximum 2 g daily) for 14 days.^{261 311} Patients usually are no longer contagious 48 hours after initiation of anti-infective therapy.²⁶¹ Eradication of the organism should be confirmed by 2 consecutive negative cultures following completion of therapy.^{261 311}

Prevention of Diphtheria

Oral

Erythromycin: 40–50 mg/kg daily (maximum 2 g daily) for 7–10 days.^{261 311 455}

Elimination of Diphtheria Carrier State

Oral

Erythromycin: 40–50 mg/kg daily (maximum 2 g daily) for 7–10 days.^{311 455} Obtain follow-up cultures ≥2 weeks after completion of therapy; if cultures are positive, an additional 10-day course should be given and additional follow-up cultures obtained.^{311 455}

Lyme Disease†

Early Localized or Early Disseminated Lyme Disease†

Oral

Erythromycin: 12.5 mg/kg (up to 500 mg) 4 times daily for 14–21 days.²¹⁴ Alternatively, 30 mg/kg daily in 3 divided doses (or 250 mg 3 times daily) for 14–21 days.²⁷⁴

Nongonococcal Urethritis in Adolescents

Oral

Erythromycin (base): 500 mg 4 times daily for 7 days.²²⁸ Alternatively, 666 mg every 8 hours for ≥7 days.^{242 262} For recurrent and persistent urethritis, CDC recommends 500 mg 4 times daily for 7 days in conjunction with a single dose of oral metronidazole (2 g).²²⁸

Erythromycin (ethylsuccinate): 800 mg 4 times daily for 7 days.^{228 268 f} For recurrent and persistent urethritis, CDC recommends 800 mg 4 times daily for 7 days in conjunction with a single dose of oral metronidazole (2 g).²²⁸

Pertussis

Treatment or Prevention of Pertussis

Oral

Erthromycin (base or stearate): 40–50 mg/kg daily (maximum 2 g daily) in divided doses for 14 days.^{263 311 455}

Prevention of Bacterial Endocarditis†

Patients Undergoing Certain Dental, Oral, Respiratory Tract, or Esophageal Procedures†

Oral

Erythromycin (ethylsuccinate): 20 mg/kg 2 hours before the procedure and 10 mg/kg 6 hours later.³⁰²

Erythromycin (stearate): 20 mg/kg 2 hours before the procedure and 10 mg/kg 6 hours later.³⁰²

Adults

General Adult Dosage

Treatment of Infections

Oral

Erythromycin (base): 250 mg every 6 hours,^{262 d e} 333 mg every 8 hours,^{242 262 d} or 500 mg every 12 hours.^{242 262 d e} In severe infections, dosage may be increased up to 4 g daily; however, a twice-daily dosing schedule is not recommended when dosages exceeding 1 g daily are administered.^{242 262 e}

Erythromycin (estolate): 250 mg every 6 hours.ⁱ In severe infections, dosage may be increased up to 4 g daily.ⁱ

Erythromycin (ethylsuccinate): 400 mg every 6 hours.^{268 f} Dosage up to 4 g daily may be used for severe infections.^{268 f}

Erythromycin (stearate): 250 mg every 6 hours or 500 mg every 12 hours. In severe infections, dosage may be increased up to 4 g daily; however, a twice-daily dosing schedule is not recommended when dosage is >1 g daily.²⁶³

Pharyngitis and Tonsillitis

Oral

Erythromycin (base): 250 mg every 6 hours,^{262 d e} 333 mg every 8 hours,^{242 262 d} or 500 mg every 12 hours^{242 262 d e} for 10 days.

Amebiasis

Entamoeba histolytica Infections

Oral

Erythromycin (base or stearate): 250 mg every 6 hours,^{242 d e} 333 mg every 8 hours,^{242 263} or 500 mg every 12 hours^{242 263 d} for 10–14 days.

Erythromycin (estolate): 250 mg 4 times daily for 10–14 days.ⁱ

Erythromycin (ethylsuccinate): 400 mg 4 times daily for 10–14 days.^{268 f}

Anthrax†

IV

Erythromycin (lactobionate): 15–20 mg/kg (up to 4 g) daily given in divided doses every 6 hours.²¹⁸

Must be used in multiple-drug regimens that initially include IV ciprofloxacin or IV doxycycline and 1 or 2 other anti-infectives predicted to be effective.^{216 347}

Duration of treatment is 60 days if anthrax occurred as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism.^{216 347}

Chancroid†

Oral

Erythromycin (base): 500 mg 3–4 times daily for 7 days.^{228 248}

Erythromycin (ethylsuccinate): 800 mg 4 times daily for 7 days.²⁴⁸

Chlamydial Infections

Uncomplicated Urethral, Endocervical, or Rectal Infections

Oral

Erythromycin (base or stearate): 500 mg 4 times daily for 7 days.^{228 248 242 262 263 d e} Alternatively, 666 mg every 8 hours for 7 days.^{242 262 263} If these regimens are not tolerated in pregnant women, a dosage of 500 mg every 12 hours, 333 mg every 8 hours, or 250 mg 4 times daily for at least 14 days.^{228 242 262 263}

Erythromycin (estolate): 500 mg 4 times daily for 7 daysⁱ

Erythromycin (ethylsuccinate): 800 mg 4 times daily for 7 days.^{228 248} If this regimen is not tolerated in pregnant women, a dosage of 400 mg 4 times daily for 14 days may be used.²²⁸

Presumptive Treatment of Chlamydial Infections in Adults with Gonorrhea

Oral

Erythromycin (base): 500 mg 4 times daily for 7 days.²²⁸

Erythromycin (ethylsuccinate): 800 mg 4 times daily for 7 days.²²⁸

Lymphogranuloma venereum†

Oral

Erythromycin (base): 500 mg 4 times daily for 21 days.^{228 248}

Erythromycin (ethylsuccinate): 800 mg 4 times daily for 21 days.²⁴⁸

Diphtheria

Treatment of Diphtheria

Oral

Erythromycin: 40–50 mg/kg daily (maximum 2 g daily) for 14 days.^{261 311} Patients usually are no longer contagious 48 hours after initiation of anti-infective therapy.²⁶¹ Eradication of the organism should be confirmed by 2 consecutive negative cultures following completion of therapy.^{261 311}

Prevention of Diphtheria

Oral

Erythromycin: 1 g daily for 7–10 days.^{261 455}

Elimination of Diphtheria Carrier State

Oral

Erythromycin: 1 g daily for 7–10 days.^{311 455} Obtain follow-up cultures ≥2 weeks after completion of therapy; if cultures are positive, an additional 10-day course should be given and additional follow-up cultures obtained.^{311 455}

Granuloma Inguinale (Donovanosis)†

Oral

Erythromycin (base): 500 mg 4 times daily for ≥3 weeks or until all lesions have healed completely;²²⁸ consider adding IV aminoglycoside (e.g., gentamicin) if improvement is not evident within the first few days of therapy and in HIV-infected patients.²²⁸

Relapse can occur 6–18 months after apparently effective treatment.²²⁸

Legionnaires' Disease

Oral

Erthromycin (base, ethylsuccinate, or stearate): 1–4 g daily in divided doses has been used alone or in conjunction with rifampin.^{242 311 262 263 268 311 452 453 d e f} Usual duration is 10–21 days.^{311 452 453}

IV

Erythromycin (lactobionate): 1–4 g daily in divided doses has been used alone or in conjunction with rifampin.^{311 452 453 c} After a response is obtained, rifampin can be discontinued and therapy changed to oral erythromycin.^{311 452 453} Usual duration is 10–21 days.^{311 452 453}

Early Localized or Early Disseminated Lyme Disease†

Oral

Erythromycin: 500 mg 4 times daily for 14–21 days.²¹⁴ Alternatively, 250 mg 4 time daily for 14–21 days.²⁷⁴

Nongonococcal Urethritis

Oral

Erythromycin (base or stearate): 500 mg 4 times daily for 7 days.^{228 248 263} Alternatively, 666 mg every 8 hours for ≥7 days.^{242 262 263} For recurrent and persistent urethritis, CDC recommends 500 mg 4 times daily for 7 days in conjunction with a single dose of oral metronidazole (2 g).²²⁸

Erythromycin (ethylsuccinate): 800 mg 4 times daily for 7 days.^{228 248 268 f}

Exgest LA

Generic Name: guaifenesin and phenylpropanolamine (gwye FEN e sin/fen ill proe pa NOLE a meen)

Brand Names: Ami-Tex LA, Banex-LA, Coldloc-LA, Dayquil Sinus Pressure and Congestion, Despec, Entex LA, Exgest LA, G-Vent, Guaifenex PPA 75, Guaivent, Guiatex LA, Naldecon-EX Pediatric, Nasahist LA, Phentex-LA, Phenylfenesin LA, Poly-Vent, Profen LA, Stamoist LA, Triaminic Expectorant, Vanex-LA

What is Exgest LA (guaifenesin and phenylpropanolamine)?

Guaifenesin is an expectorant. It is used to break up congestion and mucous to make breathing easier. Guaifenesin thins mucous, increases lubrication of the respiratory tract (lungs, nose and throat), and increases the removal of mucous.

Phenylpropanolamine is a decongestant. It constricts (shrinks) blood vessels (veins and arteries), which reduces swelling of mucous membranes in areas such as the nose and sinuses.

Guaifenesin and phenylpropanolamine is used to treat the symptoms of the common cold and of infections of the sinuses, lungs, and throat.

Phenylpropanolamine, an ingredient in this product, has been associated with an increased risk of hemorrhagic stroke (bleeding into the brain or into tissue surrounding the brain) in women. Men may also be at risk. Although the risk of hemorrhagic stroke is low, the U.S. Food and Drug Administration (FDA) recommends that consumers not use any products that contain phenylpropanolamine.

Guaifenesin and phenylpropanolamine may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about Exgest LA (guaifenesin and phenylpropanolamine)?

Phenylpropanolamine, an ingredient in this product, has been associated with an increased risk of hemorrhagic stroke (bleeding into the brain or into tissue surrounding the brain) in women. Men may also be at risk. Although the risk of hemorrhagic stroke is low, the U.S. Food and Drug Administration (FDA) recommends that consumers not use any products that contain phenylpropanolamine.

Drink plenty of extra fluids while taking this medication. Do not crush or chew the tablets. Swallow them whole or break them in half where they are scored to make them easier to swallow if needed.

Who should not take Exgest LA (guaifenesin and phenylpropanolamine)?

Do not take guaifenesin and phenylpropanolamine if you have taken a monoamine oxidase inhibitor (MAOI) such as isocarboxazid (Marplan), phenelzine (Nardil), or tranylcypromine (Parnate) in the last 14 days. A dangerous drug interaction could occur, leading to serious side effects.

Before taking this medication, tell your doctor if you have

• 
  

  high blood pressure or any other type of heart disease,

  
  


• 
  

  diabetes,

  
  


• 
  

  a peripheral vascular disorder (poor circulation),

  
  


• 
  

  glaucoma or increased pressure in the eyes,

  
  


• 
  

  an overactive thyroid, or

  
  


• 
  

  difficulty urinating or an enlarged prostate.

  
  

You may not be able to take guaifenesin and phenylpropanolamine, or you may require a dosage adjustment or special monitoring during treatment if you have any of the conditions listed above.

Guaifenesin and phenylpropanolamine is in the FDA pregnancy category C. This means that it is not known whether guaifenesin and phenylpropanolamine will harm an unborn baby. Do not take this medication without first talking to your doctor if you are pregnant. This medication passes into breast milk and may harm a nursing baby. Do not take this medication without first talking to your doctor if you are breast-feeding a baby. If you are over 65 years of age, you may be more likely to experience side effects from guaifenesin and phenylpropanolamine. You may require a lower dose of this medication. Guaifenesin and phenylpropanolamine has not been approved for use by children younger than 6 years of age.

How should I take Exgest LA (guaifenesin and phenylpropanolamine)?

Take guaifenesin and phenylpropanolamine exactly as directed by your doctor. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain them to you.

Take each dose with a full glass of water. Increasing fluid intake during the day may help relieve congestion. Take guaifenesin and phenylpropanolamine with food if it causes stomach upset. Do not crush or chew the tablets. Swallow them whole or break them in half where they are scored to make them easier to swallow if needed. Store guaifenesin and phenylpropanolamine at room temperature away from moisture and heat.

What happens if I miss a dose?

Take the missed dose as soon as you remember. However, if it is almost time for the next dose, skip the missed dose and take only the next regularly scheduled dose. Do not take a double dose of this medication.

What happens if I overdose?

Seek emergency medical attention.

Symptoms of a guaifenesin and phenylpropanolamine overdose include vomiting, high blood pressure (headache, redness of face, blurred vision), an irregular heartbeat, and numbness of the fingers or toes.

What should I avoid while taking Exgest LA (guaifenesin and phenylpropanolamine)?

Use caution when driving, operating machinery, or performing other hazardous activities. Guaifenesin and phenylpropanolamine may cause dizziness. If you experience dizziness, avoid these activities.

Exgest LA (guaifenesin and phenylpropanolamine) side effects

No serious side effects from guaifenesin and phenylpropanolamine are expected. Seek emergency medical attention if you experience an allergic reaction (difficulty breathing; closing of your throat; swelling of your lips, tongue, or face; or hives).

Other, less serious side effects may be more likely to occur. Continue to take guaifenesin and phenylpropanolamine and talk to your doctor if you experience

• 
  

  dizziness or headache;

  
  


• 
  

  nervousness, restlessness, or insomnia;

  
  


• 
  

  nausea or stomach upset; or

  
  


• 
  

  difficulty urinating.

  
  

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome.

What other drugs will affect Exgest LA (guaifenesin and phenylpropanolamine)?

Do not take guaifenesin and phenylpropanolamine if you have taken a monoamine oxidase inhibitor (MAOI) such as isocarboxazid (Marplan), phenelzine (Nardil), or tranylcypromine (Parnate) in the last 14 days. A dangerous drug interaction could occur, leading to serious side effects.

Heart medications such as methyldopa (Aldomet), reserpine (Serpalan, Serpasil), and guanethidine (Ismelin) may have decreased effects. Talk to your doctor before taking guaifenesin and phenylpropanolamine if you are taking any of these medications.

Do not take other over-the-counter cough, cold, allergy, diet, or sleep aids while taking guaifenesin and phenylpropanolamine without first talking to your doctor or pharmacist. Other medications may also contain guaifenesin, phenylpropanolamine, or other similar drugs. You may accidentally take too much of these medicines.

Drugs other than those listed here may also interact with guaifenesin and phenylpropanolamine. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines.

More Exgest LA resources

• Exgest LA Side Effects (in more detail)
• Exgest LA Use in Pregnancy & Breastfeeding
• Drug Images
• Exgest LA Drug Interactions
• Exgest LA Support Group
• 0 Reviews for Exgest LA - Add your own review/rating

Compare Exgest LA with other medications

• Cough and Nasal Congestion

Where can I get more information?

• Your pharmacist has additional information about guaifenesin and phenylpropanolamine written for health professionals that you may read.

What does my medication look like?

Guaifenesin and phenylpropanolamine is available with a prescription under several brand names. Ask your pharmacist any questions you have about this medication, especially if it is new to you.

• 
  

  Entex LA, 400 mg of guaifenesin and 75 mg of phenylpropanolamine--orange, scored tablets

  
  


• 
  

  Exgest LA, 400 mg of guaifenesin and 75 mg of phenylpropanolamine--white, oval-shaped, scored, long-acting tablets with blue speckles

  
  


• 
  

  Dura-Vent, 600 mg of guaifenesin and 75 mg of phenylpropanolamine--white, scored tablets

  
  

See also: Exgest LA side effects (in more detail)

Par Pharmaceutical

Address Par Pharmaceutical, 300 Tice Boulevard Woodcliff Lake, NJ 07677 Contact Details Phone: (201) 802-4000 Website: http://www.parpharm.com/ Careers: http://www.parpharm.com/index.php?option=com_content&view=article&id=78&Itemid=18

estradiol topical

Generic Name: estradiol (topical) (ess tra DYE ole)

Brand Names: Estrace Vaginal Cream, Estring

What is estradiol?

Estradiol (a form of estrogen) is a female sex hormone necessary for many processes in the body. Estradiol vaginal products release estrogen that is absorbed directly through the skin of the vaginal wall.

Estradiol topical is used to treat certain symptoms of menopause such as dryness, burning, and itching of the vaginal area and urgency or irritation with urination.

Estradiol may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about estradiol?

Estradiol increases the risk of developing a condition (endometrial hyperplasia) that may lead to cancer of the lining of the uterus. Taking progestins, another hormone drug, while using estradiol lowers the risk of developing this condition. Therefore, if your uterus has not been removed, your doctor may prescribe a progestin for you to take together while using estradiol. Visit your doctor regularly and report any unusual vaginal bleeding right away.

Treatment with estradiol long-term may increase the risk of stroke. Because of this risk, you should contact your doctor or healthcare provider to discuss your individual risks and benefits before taking estradiol long-term. You should also talk to your doctor or healthcare provider on a regular basis (for example, every 3-6 months) about whether you should continue this treatment.

Have yearly physical exams and examine your breasts for lumps on a monthly basis while using estradiol.

Do not use this medication if you are pregnant.

The Women's Health Initiative (WHI) study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50-79 years of age) during 5 years of treatment with oral conjugated estrogens combined with medroxyprogesterone acetate.

The Women's Health Initiative Memory Study (WHIMS) found that postmenopausal women 65 years of age or older who were treated with oral conjugated estrogens plus medroxyprogesterone acetate had an increased risk of developing dementia. It is unknown whether this finding applies to younger postmenopausal women or to women using estrogen only therapy.

What should I discuss with my healthcare provider before using estradiol?

Do not use estradiol without first talking to your doctor if you have

• 
  

  a circulation, bleeding, or blood-clotting disorder;

  
  


• 
  

  undiagnosed, abnormal vaginal bleeding; or

  
  


• 
  

  any type of breast, uterine, or hormone-dependent cancer.

  
  

Using estradiol may be dangerous in some cases if you have any of the conditions listed above.

Before using estradiol, tell your doctor if you have

• 
  

  high blood pressure, angina, or heart disease;

  
  


• 
  

  high levels of cholesterol or triglycerides in your blood;

  
  


• liver disease;


• kidney disease;


• 
  

  asthma;

  
  


• 
  

  epilepsy;

  
  


• 
  

  migraines;

  
  


• 
  

  diabetes;

  
  


• 
  

  depression;

  
  


• 
  

  gallbladder disease;

  
  


• 
  

  uterine fibroids;

  
  


• 
  

  had a hysterectomy (uterus removed);

  
  


• 
  

  a narrow, short, or prolapsed vagina;

  
  


• 
  

  vaginal irritation; or

  
  


• 
  

  a vaginal infection.

  
  

You may not be able to use estradiol, or you may require a dosage adjustment or special monitoring during treatment if you have any of the conditions listed above.

Treatment with estradiol long-term may increase the risk of stroke. Because of this risk, you should contact your doctor or healthcare provider to discuss your individual risks and benefits before taking estradiol long-term. You should also talk to your doctor or healthcare provider on a regular basis (for example, every 3-6 months) about whether you should continue this treatment.

The Women's Health Initiative (WHI) study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50-79 years of age) during 5 years of treatment with oral conjugated estrogens combined with medroxyprogesterone acetate.

The Women's Health Initiative Memory Study (WHIMS) found that postmenopausal women 65 years of age or older who were treated with oral conjugated estrogens plus medroxyprogesterone acetate had an increased risk of developing dementia. It is unknown whether this finding applies to younger postmenopausal women or to women using estrogen only therapy.

Estradiol is in the FDA pregnancy category X. This means that estradiol will cause birth defects in an unborn baby. Do not use estradiol if you are pregnant or are planning a pregnancy. Estradiol may decrease milk flow and have other effects on milk composition. Do not use estradiol without first talking to your doctor if you are breast-feeding a baby.

How should I use estradiol?

Use estradiol exactly as directed by your doctor. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain them to you.

To use the Estring vaginal ring:

• 
  

  Squeeze the sides of the ring together and insert it into the vagina as far as possible (into the upper 1/3 of the vagina). You should not be able to feel the ring once it is in position. If you can feel it, use a finger to push it further into the vagina. It is not possible for the ring to go too far in or become lost.

  
  


• 
  

  The ring should remain in place for 90 days. It should then be removed and replaced by a new ring, if prescribed by your doctor. If at any time the ring falls out, rinse it with warm water and reinsert it. If it slides down into the lower part of the vagina, use a finger to reinsert it.

  
  


• 
  

  The ring does not need to be removed during sexual intercourse. It should not be felt by either partner. If it is bothersome, it can be removed, rinsed with warm water, and reinserted following intercourse.

  
  


• 
  

  To remove the ring, loop a finger through the ring and gently pull it from the vagina.

  
  

To use the estradiol vaginal cream:

• 
  

  Using the marked applicator provided, measure the prescribed dose of cream.

  
  


• 
  

  Lie on your back with your knees drawn up, sit, or stand in a position that allows you comfortable access to the vaginal area. To deliver the medication, gently insert the applicator deeply into your vagina and press the plunger downward to its original position.

  
  


• 
  

  Clean the applicator by pulling the plunger to remove it from the barrel. Wash it with mild soap and warm water.

  
  

Have yearly physical exams and examine your breasts for lumps on a monthly basis while using estradiol.

Store the vaginal rings and cream at room temperature away from moisture and heat.

What happens if I miss a dose?

Insert the next dose of cream or ring as soon as you remember. Continue to follow your regular schedule. Do not use two doses simultaneously unless your doctor directs otherwise.

If at any time the ring falls out, rinse it with warm water and reinsert it. If it slides down into the lower part of the vagina, use a finger to reinsert it.

What happens if I overdose?

An overdose of estradiol is unlikely to occur and is not likely to threaten life. If you do suspect an overdose, or if the medication has been ingested, call an emergency room or poison control center for advice.

What should I avoid while using estradiol?

There are no restrictions on food, beverages, or activity while using estradiol unless your doctor directs otherwise.

Estradiol side effects

Estradiol increases the risk of developing a condition (endometrial hyperplasia) that may lead to cancer of the lining of the uterus. Taking progestins, another hormone drug, while using estradiol lowers the risk of developing this condition. Therefore, if your uterus has not been removed, your doctor may prescribe a progestin for you to take together while using estradiol. Visit your doctor regularly and report any unusual vaginal bleeding right away.

Treatment with estradiol long-term may increase the risk of stroke. Because of this risk, you should contact your doctor or healthcare provider to discuss your individual risks and benefits before taking estradiol long-term. You should also talk to your doctor or healthcare provider on a regular basis (for example, every 3-6 months) about whether you should continue this treatment.

If you experience any of the following serious side effects, stop using estradiol and seek emergency medical attention:

• 
  

  an allergic reaction (difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives);

  
  


• 
  

  shortness or breath or pain in the chest;

  
  


• 
  

  a painful, red, swollen leg;

  
  


• 
  

  abnormal vaginal bleeding;

  
  


• 
  

  pain, swelling, or tenderness in the abdomen;

  
  


• 
  

  severe headache or vomiting, dizziness, faintness or changes in vision or speech;

  
  


• 
  

  yellowing of the skin or eyes; or

  
  


• 
  

  a lump in a breast.

  
  

Other, less serious side effects may be more likely to occur. Continue to use estradiol and talk to your doctor if you experience

• 
  

  decreased appetite, nausea, or vomiting;

  
  


• 
  

  swollen breasts;

  
  


• 
  

  acne or skin color changes;

  
  


• 
  

  decreased sex drive;

  
  


• 
  

  migraine headaches or dizziness;

  
  


• 
  

  vaginal pain, dryness, or discomfort;

  
  


• 
  

  water retention (swollen hands, feet, or ankles);

  
  


• 
  

  depression; or

  
  


• 
  

  changes in your menstrual cycle or break-through bleeding.

  
  

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome.

Estradiol Dosing Information

Usual Adult Dose for Atrophic Urethritis:

Vaginal cream:
1 to 4 grams intravaginally once a day for 1 to 2 weeks. Gradually, the initial dosage should be reduced to one-half and continued for a similar time. Following resolution of symptoms, a maintenance dosage of 1 gram intravaginally 1 to 3 times a week should be administered.

Vaginal ring:
2 mg estradiol vaginal ring inserted into the upper vaginal area. The ring remains continuously in place for 3 months. Should expulsion or removal occur during a 90 day treatment period, reinsertion is possible. The ring should be rinsed in luke warm water prior to reinsertion. Retention beyond 90 days results in underdosage and loss of efficacy.

Vaginal tablet: 10 mcg
Initial dose: one tablet inserted into the vagina once daily for two weeks.
Maintenance dose: one tablet inserted into the vagina twice weekly.

Usual Adult Dose for Atrophic Vaginitis:

Vaginal cream:
1 to 4 grams intravaginally once a day for 1 to 2 weeks. Gradually, the initial dosage should be reduced to one-half and continued for a similar time. Following resolution of symptoms, a maintenance dosage of 1 gram intravaginally 1 to 3 times a week should be administered.

Vaginal ring:
2 mg estradiol vaginal ring inserted into the upper vaginal area. The ring remains continuously in place for 3 months. Should expulsion or removal occur during a 90 day treatment period, reinsertion is possible. The ring should be rinsed in luke warm water prior to reinsertion. Retention beyond 90 days results in underdosage and loss of efficacy.

Vaginal tablet: 10 mcg
Initial dose: one tablet inserted into the vagina once daily for two weeks.
Maintenance dose: one tablet inserted into the vagina twice weekly.

What other drugs will affect estradiol?

Before using estradiol, tell your doctor if you are taking any of the following medicines:

• 
  

  an anticoagulant (blood thinner) such as warfarin (Coumadin);

  
  


• 
  

  a thyroid medication such as levothyroxine (Synthroid, Levoxyl, Levothroid, and others);

  
  


• 
  

  insulin or an oral diabetes medicine such as glipizide (Glucotrol), glyburide (Diabeta, Micronase), and others; or

  
  


• 
  

  tamoxifen (Nolvadex).

  
  

A dosage adjustment or special monitoring may be required during treatment if you are taking any of the medicines listed above.

Do not use other vaginal products at the same times as estradiol without first talking to your doctor.

Drugs other than those listed here may also interact with estradiol. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines, including vitamins, minerals, and herbal products.

More estradiol resources

• Estradiol Dosage
• Estradiol Use in Pregnancy & Breastfeeding
• Estradiol Drug Interactions
• Estradiol Support Group
• 21 Reviews for Estradiol - Add your own review/rating

• Estring Prescribing Information (FDA)


• Estring Ring MedFacts Consumer Leaflet (Wolters Kluwer)


• Estring Advanced Consumer (Micromedex) - Includes Dosage Information


• Vagifem Prescribing Information (FDA)


• Vagifem MedFacts Consumer Leaflet (Wolters Kluwer)

Compare estradiol with other medications

• Atrophic Urethritis
• Atrophic Vaginitis
• Hypoestrogenism

Where can I get more information?

• Your pharmacist has additional information about estradiol written for health professionals that you may read.

What does my medication look like?

Estradiol is available with a prescription under the brand name Estrace as a vaginal cream and under the brand name Estring as a vaginal ring. Other brand or generic formulations may also be available. Ask your pharmacist any questions you have about this medication, especially if it is new to you.

• 
  

  Estrace Vaginal Cream-42.5 g tube with a plastic applicator

  
  


• 
  

  Estring Vaginal Ring-2 mg