Neosporin

Dosage Form: Ophthalmic Ointment

Description

Neosporin OPHTHALMIC OINTMENT (neomycin and polymyxin B sulfates and bacitracin zinc ophthalmic ointment) is a sterile antimicrobial ointment for ophthalmic use. Each gram contains: neomycin sulfate equivalent to 3.5 mg neomycin base, polymyxin B sulfate equivalent to 10,000 polymyxin B units, bacitracin zinc equivalent to 400 bacitracin units, and white petrolatum, q.s.

Neomycin sulfate is the sulfate salt of neomycin B and C, which are produced by the growth of Streptomyces fradiae Waksman (Fam. Streptomycetaceae). It has a potency equivalent of not less than 600 µg of neomycin standard per mg, calculated on an anhydrous basis. The structural formulae are:

Polymyxin B sulfate is the sulfate salt of polymyxin B1 and B2, which are produced by the growth of Bacillus polymyxa (Prazmowski) Migula (Fam. Bacillaceae). It has a potency of not less than 6,000 polymyxin B units per mg, calculated on an anhydrous basis. The structural formulae are:

Bacitracin zinc is the zinc salt of bacitracin, a mixture of related cyclic polypeptides (mainly bacitracin A) produced by the growth of an organism of the licheniformis group of Bacillus subtilis var Tracy. It has a potency of not less than 40 bacitracin units per mg. The structural formula is:

Clinical Pharmacology

A wide range of antibacterial action is provided by the overlapping spectra of neomycin, polymyxin B sulfate, and bacitracin.

Neomycin is bactericidal for many gram-positive and gram-negative organisms. It is an aminoglycoside antibiotic which inhibits protein synthesis by binding with ribosomal RNA and causing misreading of the bacterial genetic code.

Polymyxin B is bactericidal for a variety of gram-negative organisms. It increases the permeability of the bacterial cell membrane by interacting with the phospholipid components of the membrane.

Bacitracin is bactericidal for a variety of gram-positive and gram-negative organisms. It interferes with bacterial cell wall synthesis by inhibition of the regeneration of phospholipid receptors involved in peptidoglycan synthesis.

Microbiology: Neomycin sulfate, polymyxin B sulfate, and bacitracin zinc together are considered active against the following microorganisms: Staphylococcus aureus, streptococci including Streptococcus pneumoniae, Escherichia coli, Haemophilus influenzae, Klebsiella/Enterobacter species, Neisseria species, and Pseudomonas aeruginosa. The product does not provide adequate coverage against Serratia marcescens.

Indications and Usage

Neosporin Ophthalmic Ointment is indicated for the topical treatment of superficial infections of the external eye and its adnexa caused by susceptible bacteria. Such infections encompass conjunctivitis, keratitis and keratoconjunctivitis, blepharitis and blepharoconjunctivitis.

Contraindications

Neosporin Ophthalmic Ointment is contraindicated in individuals who have shown hypersensitivity to any of its components.

Warnings

NOT FOR INJECTION INTO THE EYE. Neosporin OPHTHALMIC OINTMENT should never be directly introduced into the anterior chamber of the eye. Ophthalmic ointments may retard corneal wound healing.

Topical antibiotics, particularly neomycin sulfate, may cause cutaneous sensitization. A precise incidence of hypersensitivity reactions (primarily skin rash) due to topical antibiotics is not known. The manifestations of sensitization to topical antibiotics are usually itching, reddening, and edema of the conjunctiva and eyelid. A sensitization reaction may manifest simply as a failure to heal. During long-term use of topical antibiotic products, periodic examination for such signs is advisable, and the patient should be told to discontinue the product if they are observed. Symptoms usually subside quickly on withdrawing the medication. Application of products containing these ingredients should be avoided for the patient thereafter (see PRECAUTIONS: General).

Precautions

General

As with other antibiotic preparations, prolonged use of Neosporin Ophthalmic Ointment may result in overgrowth of nonsusceptible organisms including fungi. If superinfection occurs, appropriate measures should be initiated.

Bacterial resistance to Neosporin Ophthalmic Ointment may also develop. If purulent discharge, inflammation, or pain become aggravated, the patient should discontinue use of the medication and consult a physician.

There have been reports of bacterial keratitis associated with the use of topical ophthalmic products in multiple-dose containers which have been inadvertently contaminated by patients, most of whom had a concurrent corneal disease or a disruption of the ocular epithelial surface (see PRECAUTIONS: Information for Patients).

Allergic cross-reactions may occur which could prevent the use of any or all of the following antibiotics for the treatment of future infections: kanamycin, paromomycin, streptomycin, and possibly gentamicin.

Information for Patients

Patients should be instructed to avoid allowing the tip of the dispensing container to contact the eye, eyelid, fingers, or any other surface. The use of this product by more than one person may spread infection.

Patients should also be instructed that ocular products, if handled improperly, can become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated products (see PRECAUTIONS: General).

If the condition persists or gets worse, or if a rash or allergic reaction develops, the patient should be advised to stop use and consult a physician. Do not use this product if you are allergic to any of the listed ingredients.

Keep tightly closed when not in use. Keep out of reach of children.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals to evaluate carcinogenic or mutagenic potential have not been conducted with polymyxin B sulfate or bacitracin. Treatment of cultured human lymphocytes in vitrowith neomycin increased the frequency of chromosome aberrations at the highest concentration (80 µg/mL) tested; however, the effects of neomycin on carcinogenesis and mutagenesis in humans are unknown.

Polymyxin B has been reported to impair the motility of equine sperm, but its effects on male or female fertility are unknown. No adverse effects on male or female fertility, litter size or survival were observed in rabbits given bacitracin zinc 100 gm/ton of diet.

Pregnancy

Teratogenic Effects

Pregnancy Category C. Animal reproduction studies have not been conducted with neomycin sulfate, polymyxin B sulfate, or bacitracin, It is also not known whether Neosporin Ophthalmic Ointment can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Neosporin Ophthalmic Ointment should be given to a pregnant woman only if clearly needed.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Neosporin Ophthalmic Ointment is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Adverse Reactions

Adverse reactions have occurred with the anti-infective components of Neosporin Ophthalmic Ointment. The exact incidence is not known. Reactions occurring most often are allergic sensitization reactions including itching, swelling, and conjunctival erythema (see WARNINGS). More serious hypersensivity reactions, including anaphylaxis, have been reported rarely.

Local irritation on instillation has also been reported.

Dosage and Administration

Apply the ointment every 3 or 4 hours for 7 to 10 days, depending on the severity of the infection.

How Supplied

Tube of 1/8 oz (3.5 g) with ophthalmic tip (NDC 0081-0732-86).

Caution: Federal law prohibits dispensing without a prescription.

Store at 15° to 25°C (59° to 77°F).

Manufactured by:

Burroughs Wellcome Inc.

Kirkland; Que., Canada H9H 4J4 for

BURROUGHS WELLCOME CO.

Research Triangle Park, NC 27709

Neosporin  neomycin sulfate, polymyxin b sulfate and bacitracin zinc  ointment

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0081-0732 Route of Administration OPHTHALMIC DEA Schedule

INGREDIENTS Name (Active Moiety) Type Strength neomycin sulfate (neomycin) Active 3.5 MICROGRAM  In 1 GRAM polymyxin B sulfate (polymyxin B) Active 10000 UNITS  In 1 GRAM bacitracin zinc (bacitracin) Active 400 UNITS  In 1 GRAM white petrolatum Inactive

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0081-0732-86 3.5 g (GRAM) In 1 TUBE None

Revised: 10/2006Burroughs Wellcome Inc.

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• Blepharitis
• Blepharoconjunctivitis
• Conjunctivitis, Bacterial
• Keratitis
• Keratoconjunctivitis

Eltrombopag

Class: Hematopoietic Agents
ATC Class: B02BX05
VA Class: BL400
Chemical Name: 3′-{(2Z)-2-[1-(3, 4-dimethylphenyl)-3-methyl-5-oxo-1, 5-dihydro-4H-pyrazol-4-ylidene] hydrazino}-2′-hydroxy-3-biphenylcarboxylic acid-2-aminoethanol (1:2)
Molecular Formula: C₂₅H₂₂N₄O₄2 ©₂H₇NO)
CAS Number: 496775-62-3
Brands: Promacta

• 
  

  Risk of hepatotoxicity.¹ (See Hepatotoxicity under Cautions and also see Laboratory Monitoring under Cautions.)

  
  


• 
  

  Measure serum ALT, AST, and bilirubin concentrations prior to initiation of eltrombopag therapy, every 2 weeks during the dosage adjustment phase, then monthly once a stable dosage has been achieved.¹

  
  


• 
  

  If serum bilirubin concentration is elevated, also obtain a fractionated bilirubin concentration.¹

  
  


• 
  

  In patients who develop liver function test abnormalities, repeat these tests within 3–5 days to confirm the results; if an abnormality is confirmed, monitor liver function tests weekly until the abnormality resolves, stabilizes, or returns to baseline.¹

  
  


• 
  

  Discontinue eltrombopag therapy if serum ALT levels increase to ≥3 times the ULN and are progressive, persistent (≥4 weeks), or are accompanied by an increased direct bilirubin concentration, clinical symptoms of hepatotoxicity, or evidence of hepatic decompensation.¹

  
  

REMS:

FDA approved a REMS for eltrombopag olamine to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of eltrombopag olamine and consists of the following: medication guide, elements to assure safe use, and implementation system. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Small-molecule thrombopoietin-receptor agonist.^{1 2}

Uses for Eltrombopag

Idiopathic Thrombocytopenic Purpura

Treatment of chronic idiopathic thrombocytopenic purpura (ITP; also known as immune thrombocytopenic purpura) in patients who have had an inadequate response to corticosteroids, immunoglobulins, or splenectomy and in whom the degree of thrombocytopenia and clinical status increase bleeding risk.^{1 2 3}

Should not be used to normalize platelet counts since excessive increases in platelet count may increase the risk of thromboembolic complications.^{1 8 9}

Not indicated for the treatment of thrombocytopenia associated with myelodysplastic syndrome or thrombocytopenia associated with any condition other than chronic ITP.^{1 9}

Not indicated for the treatment of thrombocytopenia in patients with chronic liver disease.^{8 9}

Eltrombopag Dosage and Administration

General

Restricted Distribution

• 
  

  Because of hepatotoxicity and other risks, eltrombopag is available only under a restricted distribution program (PROMACTACARES).^{1 7} Only prescribers and patients registered with the program are able to prescribe, administer, or receive eltrombopag.^{1 7} Contact 877-9-PROMACTA for additional information and to enroll in GlaxoSmithKline's PROMACTACARES program for eltrombopag.^{1 7}

  
  


• 
  

  FDA required and approved a Risk Evaluation and Mitigation Strategy (REMS) for eltrombopag.¹⁰ Goals are to promote informed risk-benefit decisions before initiating the drug; to ensure appropriate use of the drug while patients are receiving therapy; and to establish the overall long-term safety and safe use of the drug by periodically monitoring all patients for various adverse effects.¹⁰

  
  

Administration

Oral Administration

Administer orally 1 hour before or 2 hours after a meal because food may decrease the rate and extent of absorption.¹

Do not administer within 4 hours of other drugs, food, or supplements that contain polyvalent cations (e.g., iron, calcium, aluminum, magnesium, selenium, zinc).¹ Consider administration of the drug in the evening, if possible (unless patients are also taking an antacid preparation containing polyvalent cations at that time), since calcium-containing food (e.g., dairy products) is more frequently consumed at breakfast.⁴

Dosage

Available as eltrombopag olamine; dosage expressed in terms of eltrombopag.¹

Adults

Idiopathic Thrombocytopenic Purpura

Oral

Usual initial dosage: 50 mg daily.¹

Adjust dosage to achieve and maintain a platelet count of ≥50,000/mm³.¹ If platelet count is <50,000/mm³ after at least 2 weeks of eltrombopag treatment, increase daily dosage by 25 mg, up to a maximum daily dosage of 75 mg. ¹ If the platelet count has not reached a level sufficient to avoid a clinically important bleeding episode after 4 weeks at the maximum daily dosage, discontinue eltrombopag.¹

Reduce the daily dosage by 25 mg if the platelet count is between 200,000/mm³ and 400,000/mm³ at any time during eltrombopag therapy; perform follow-up assessment 2 weeks later to assess the effect of the lower dosage before additional dosage adjustments are made.¹

Do not administer eltrombopag if the platelet count is >400,000/mm³.¹ If therapy is interrupted, assess the platelet count twice weekly and resume eltrombopag olamine at a dosage reduced by 25 mg daily once the platelet count is <150,000/mm³.¹ If the platelet count is persistently elevated (e.g., >400,000/mm³ after 2 weeks at the lowest dosage), discontinue eltrombopag permanently.¹

Prescribing Limits

Adults

Idiopathic Thrombocytopenic Purpura

Oral

Maximum daily dosage: 75 mg.¹ Do not give more often than once daily.¹

Special Populations

Hepatic Impairment

In patients with moderate or severe hepatic impairment, decrease initial dosage to 25 mg daily.^{1 8 9} (See Hepatotoxicity under Cautions and also Laboratory Monitoring under Cautions.)

East Asian Ancestry

In patients of East Asian ancestry (e.g., Chinese, Japanese, Taiwanese, Korean), decrease initial dosage to 25 mg daily.¹ (See East Asian Ancestry under Cautions.)

Cautions for Eltrombopag

Contraindications

• 
  

  The manufacturer states that there are no known contraindications to the use of eltrombopag.¹

  
  

Warnings/Precautions

Warnings

Hepatotoxicity

Risk of hepatic and biliary impairment.¹ Abnormalities in serum ALT, AST, and bilirubin concentrations, predominantly grade 2 or less in severity, reported.¹ Grade 4 elevations in serum liver enzymes, as well as worsening of underlying cardiopulmonary disease and subsequent death, reported in one patient.¹

Discontinue eltrombopag if serum ALT levels increase to ≥3 times the ULN and are progressive, persistent (≥4 weeks), or are accompanied by an increased direct bilirubin concentration or clinical symptoms of hepatotoxicity or hepatic decompensation.¹ (See Laboratory Monitoring under Cautions.)

Retreatment with eltrombopag after discontinuance for hepatotoxicity is not recommended.¹ However, may consider retreatment if the anticipated clinical benefit of eltrombopag outweighs the potential risk of hepatotoxicity.¹ If treatment is reinitiated, evaluate serum ALT, AST, and bilirubin concentrations weekly during the dosage adjustment phase.¹ If abnormal liver function tests persist, worsen, or recur, permanently discontinue eltrombopag. ¹

General Precautions

Bone Marrow Reticulin Deposition and Bone Marrow Fibrosis

Thrombopoietin (TPO)-receptor agonists increase the risk of development or progression of reticulin fiber deposition within the bone marrow, thereby increasing the risk for bone marrow fibrosis or myelofibrosis.¹ Risk for bone marrow fibrosis with cytopenias in patients receiving eltrombopag not excluded in clinical studies.¹

Evaluate a peripheral blood smear prior to starting eltrombopag therapy and monthly thereafter once a stable dosage has been achieved.¹ Examination of the peripheral blood smear should include establishment of a baseline level of cellular morphologic abnormalities; monthly evaluations should include examinations for new or worsening morphologic abnormalities (e.g., teardrop or nucleated erythrocytes, immature leukocytes).¹ Perform CBC monthly to evaluate new or worsening cytopenias.¹ If a new or worsening morphologic abnormality or cytopenia develops, discontinue eltrombopag and consider a bone marrow biopsy, with additional staining for fibrosis.¹

Thrombocytopenia and Hemorrhage Following Eltrombopag Discontinuance

Risk of thrombocytopenia, which may be more severe than prior to therapy, after discontinuance of eltrombopag.¹ May result in increased risk of bleeding, especially if eltrombopag is discontinued while the patient is receiving concomitant antiplatelet or anticoagulation therapy.¹ Transient decrease in platelet count to levels lower than baseline reported in clinical studies following discontinuance of eltrombopag.¹ Serious hemorrhagic events occurring within 1 month of discontinuance of eltrombopag and requiring the use of additional ITP therapy also reported in patients with severe thrombocytopenia in clinical studies.¹

Perform CBC with platelet count weekly for at least 4 weeks following discontinuance of eltrombopag.¹ Consider additional ITP therapy for worsening thrombocytopenia.¹

Thrombosis/Thromboembolism

Risk of thrombosis or a thromboembolic complication as a result of excessive increase in platelet count secondary to excessive dosages of eltrombopag or medication errors resulting in excessive dosages.¹ Thrombosis also may occur even with normal or low platelet counts.⁷

Use eltrombopag with caution in patients with known risk factors for thromboembolism (e.g., factor V Leiden, antithrombin III [ATIII] deficiency, antiphospholipid syndrome).¹ To minimize the risk for a thrombotic or thromboembolic complication, do not use eltrombopag to normalize platelet counts; use drug only to maintain a platelet count of ≥50,000/mm³ according to the dosage adjustment guidelines.^{1 8 9} (See Idiopathic Thrombocytopenic Purpura under Dosage and Administration.)

Thrombosis of the portal venous system reported in patients with chronic liver disease receiving eltrombopag.^{8 9} Platelet counts >200,000/mm³ observed in some patients who received eltrombopag and experienced portal venous thrombosis.^{8 9} Eltrombopag is not indicated for the treatment of thrombocytopenia in patients with chronic liver disease.^{8 9}

Malignancy

Possible risk of progression to a hematologic malignancy, especially in patients with myelodysplastic syndrome (MDS), secondary to stimulation of the TPO receptor present on the surface of hematopoietic cells by eltrombopag. ¹ Do not use eltrombopag to treat or correct thrombocytopenia related to an underlying hematologic cause (e.g., myelodysplasia) or resulting from chemotherapy; use eltrombopag only for thrombocytopenia associated with chronic ITP.¹

Cataracts

Development or worsening of cataracts reported.¹ Perform a baseline ocular examination prior to eltrombopag therapy; while on therapy, monitor periodically for signs and symptoms of cataracts.¹

Laboratory Monitoring

Obtain CBC, including platelet count and peripheral blood smear, prior to starting therapy, weekly during the dosage adjustment phase, then monthly once a stable dosage has been achieved.¹ Baseline peripheral blood smears should establish the presence and extent of red and white cell abnormalities.¹ Once eltrombopag is discontinued, evaluate CBC with platelet count weekly for at least 4 weeks to monitor for worsening thrombocytopenia.¹

Evaluate serum ALT, AST, and bilirubin concentrations prior to starting therapy and every 2 weeks during the dosage adjustment phase, then monthly once a stable dosage has been achieved.¹ If serum bilirubin is elevated, also obtain a fractionated bilirubin concentration.¹ In patients who develop liver function test abnormalities, repeat these tests within 3–5 days to confirm the results; if an abnormality is confirmed, monitor liver function tests weekly until the abnormality resolves, stabilizes, or returns to baseline.¹ Discontinue eltrombopag therapy if important hepatic abnormalities occur.¹ (See Hepatotoxicity under Cautions.)

Specific Populations

Pregnancy

Category C.¹ Pregnancy registry at 888-825-5249.¹

Lactation

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

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age.^{1 7}

Geriatric Use

No substantial differences in safety and efficacy in geriatric patients ≥65 years of age relative to younger adults, but increased sensitivity cannot be ruled out.¹

Hepatic Impairment

Decreased clearance; exercise caution, adjust dosage, and monitor closely in patients with moderate or severe hepatic impairment.^{1 8 9} (See Hepatic Impairment under Dosage and Administration and also see Special Populations under Pharmacokinetics.)

Thrombosis of the portal venous system reported in patients with thrombocytopenia and chronic liver disease receiving eltrombopag.^{8 9} (See Thrombosis/Thromboembolism under Cautions.) Eltrombopag is not indicated for the treatment of thrombocytopenia in patients with chronic liver disease.^{8 9} To minimize the risk for a thrombotic or thromboembolic complication, do not use eltrombopag to normalize platelet counts; only use the drug to maintain a platelet count of ≥50,000/mm³ according to the dosage adjustment recommendations.^{1 8 9} (See Dosage under Dosage and Administration.)

Renal Impairment

Safety and efficacy of eltrombopag in patients with varying degrees of impaired renal function have not been established.¹ Closely monitor patients with impaired renal function.¹

East Asian Ancestry

Increased eltrombopag exposure reported in patients of East Asian ancestry (e.g., Chinese, Japanese, Taiwanese, Korean); dosage adjustment recommended.¹ Somewhat increased (but qualitatively similar) pharmacodynamic response also reported.¹ (See East Asian Ancestry under Dosage and Administration and also see Special Populations under Pharmacokinetics.)

Common Adverse Effects

Nausea,¹ vomiting,¹ menorrhagia,¹ myalgia,¹ paresthesia,¹ cataract,¹ dyspepsia,¹ ecchymosis,¹ thrombocytopenia,¹ increased serum transaminases (ALT, AST),¹ conjunctival hemorrhage.¹

In an extension study: headache, upper respiratory tract infection, diarrhea, nasopharyngitis.⁵

Interactions for Eltrombopag

Metabolized by CYP1A2 and CYP2C8; also undergoes glucuronidation by UGT isoenzymes 1A1 and 1A3. ¹ Inhibits CYP2C8 and CYP2C9 and the organic anion-transporting polypeptide (OATP) 1B1.¹

Drugs Affecting Hepatic Microsomal Enzymes

Moderate to strong inhibitors of CYP1A2 or CYP2C8: potential pharmacokinetic interaction (increased systemic exposure to eltrombopag).¹ Use with caution.¹

Moderate to strong inducers of CYP1A2 or CYP2C8: potential pharmacokinetic interaction (decreased systemic exposure to eltrombopag).¹

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP2C8 or CYP2C9: potential pharmacokinetic interaction (altered metabolism of CYP2C8 or CYP2C9 substrates).¹ Inhibition or induction of the metabolism of a combination of probe substrates for CYP1A2, CYP2C19, CYP2C9, or CYP3A4) following administration of eltrombopag (75 mg once daily) for 7 days to healthy male individuals not demonstrated. ¹ Probe substrates for CYP2C8 not evaluated.¹

Drugs Transported by Organic Anion-transporting Polypeptide 1B1

Substrates of organic anion-transporting polypeptide (OATP) 1B1: Potential pharmacokinetic interaction (increased concentrations of concomitantly administered OATP1BI substrates.¹ Consider reduction of OATP1B1 substrate dosage if manifestations of excessive systemic exposure to these drugs occur.¹

Drugs Affecting or Metabolized by Uridine Diphosphate-glucuronosyltransferase (UGT)

Eltrombopag inhibits uridine diphosphate-glucuronosyltransferase (UGT) isoenzymes 1A1, 1A3, 1A4, 1A6, 1A9, 2B7, and 2B15.¹

Substrates of UGTs: Potential pharmacokinetic interaction (increased systemic exposure to multiple UGT substrates.¹ Use with caution.¹

Moderate to strong inhibitors of UGT1A1 or UGT1A3: Potential pharmacokinetic interaction (increased systemic exposure to eltrombopag).¹ Use with caution.¹

Specific Drugs and Foods

Drug	Interaction	Comments
Acetaminophen	Potential increased systemic exposure to acetaminophen1	Use with caution1
Benzylpenicillin	Potential increased benzylpenicillin concentrations1	Consider reduction of benzylpenicillin dosage if manifestations of excessive systemic exposure occur1
Caffeine	Pharmacokinetics of caffeine unlikely to be affected1
Cations, polyvalent (e.g., iron, calcium, aluminum, magnesium, selenium, zinc) found in food, mineral supplements, and antacids	Reduced plasma eltrombopag concentration in patients receiving concomitant antacid therapy containing aluminum hydroxide, magnesium carbonate, and sodium alginate1 4 Reduced eltrombopag AUC reported in association with high-calcium, high-fat breakfast4	Avoid medications and foods containing polyvalent cations, including antacids, dairy products, and mineral supplements, for 4 hours before and after each dose of eltrombopag1 4
Ciprofloxacin	Potential increased systemic exposure to eltrombopag1	Use with caution1
Flurbiprofen	Pharmacokinetics of flurbiprofen unlikely to be affected1
Fluvoxamine	Potential increased systemic exposure to eltrombopag1	Use with caution1
Gemfibrozil	Potential increased systemic exposure to eltrombopag1	Use with caution1
HMG-CoA reductase inhibitors (statins; e.g., atorvastatin, fluvastatin, pravastatin, rosuvastatin)	Potential increased statin concentrations1 Increased AUC and peak plasma concentration of rosuvastatin reported following administration of single 10-mg dose of rosuvastatin in healthy adults receiving 75 mg of eltrombopag daily for 5 days1	Consider reduction of statin dosage if manifestations of excessive systemic exposure occur1 Reduction in rosuvastatin dosage by 50% was recommended for patients receiving concomitant eltrombopag in clinical trials1
Meglitinides (nateglinide, repaglinide)	Potential increased meglitinide concentrations1	Consider reduction of meglitinide dosage if manifestations of excessive systemic exposure occur1
Methotrexate	Potential increased methotrexate concentrations1	Consider reduction of methotrexate dosage if manifestations of excessive systemic exposure occur1
Midazolam	Pharmacokinetics of midazolam unlikely to be affected1
NSAIAs	Potential increased systemic exposure to NSAIAs1	Use with caution1
Omeprazole	Potential decreased systemic exposure to eltrombopag; pharmacokinetics of omeprazole unlikely to be affected1
Opiates	Potential increased systemic exposure to opiates1	Use with caution1
Rifampin	Potential decreased systemic exposure to eltrombopag1 Potential increased rifampin concentrations1 1	Consider reduction of rifampin dosage if manifestations of excessive systemic exposure occur1
Tobacco	Potential decreased systemic exposure to eltrombopag1
Trimethoprim	Potential increased systemic exposure to eltrombopag1	Use with caution1

Eltrombopag Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentrations occur 2–6 hours following oral administration.¹

Bioavailability of at least 52% reported following a single dose of 75 mg as an oral solution.¹

Onset

Increases in platelet counts generally observed within 1–2 weeks after beginning therapy.¹

Duration

Decreases in platelet counts generally observed within 1–2 weeks after discontinuance of therapy.¹

Food

Food (standard high-fat breakfast) decreases rate and extent of absorption;¹ calcium content of meal may contribute to decreased absorption.^{1 4}

Distribution

Extent

Distributes into blood cells; concentrations in blood cells about 50–79% of plasma concentrations.¹

Not known whether eltrombopag is distributed into human milk.¹

Plasma Protein Binding

>99%.¹

Elimination

Metabolism

Extensively metabolized, predominantly through pathways including cleavage, oxidation (CYP1A2 and CYP2C8), and conjugation with glucuronic acid (via UGT1A1 and UGT1A3), glutathione, or cysteine.¹

Metabolites associated with glucuronidation and oxidation detected.¹

Elimination Route

Excreted in feces (59%) and urine (31%).¹ Unchanged drug excreted in feces accounts for 20% of the dose; no unchanged drug detectable in urine.¹

Half-life

Healthy individuals: 21–32 hours.¹

Patients with ITP: 26–35 hours.¹

Special Populations

Compared with healthy individuals, the AUC for eltrombopag was 41% higher in patients with mild hepatic impairment and 80–93% higher in patients with moderate to severe hepatic impairment. ¹ A corresponding reduction (50%) in apparent clearance of eltrombopag was reported in patients with moderate or severe hepatic impairment.¹ Prolonged half-life (twofold) of eltrombopag also reported in patients with moderate or severe hepatic impairment.¹ High interpatient variability observed in the impact of hepatic impairment on eltrombopag pharmacokinetics.¹

Increased eltrombopag exposure (approximately 70%) reported in some Asian individuals of Japanese, Chinese, Taiwanese, and Korean ancestry (i.e., East Asian) with ITP as compared with non-Asian subjects (who were predominantly Caucasian).¹

Increased eltrombopag exposure (approximately 40%) reported in healthy African-American individuals in at least one clinical pharmacology study.¹ Clinical importance unknown.¹

Increased apparent eltrombopag clearance (about 27%) after adjustment for body weight difference reported in males compared with females.¹

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).¹

Actions

• 
  

  Eltrombopag olamine is a small-molecule, nonpeptide, thrombopoietin (TPO)-receptor agonist.^{1 2 3}

  
  


• 
  

  Interacts with the transmembrane domain of the TPO receptor, initiating a cascade of intracellular signaling events leading to proliferation and differentiation of bone marrow progenitor cells within the megakaryocytic lineage and subsequently increasing the production of platelets.^{1 2 3}

  
  


• 
  

  Eltrombopag (up to 150 mg daily for 5 days) did not prolong QT or QT corrected for rate (QT_c) interval in healthy adults.¹

  
  

Advice to Patients

• 
  

  Importance of understanding that treatment can only be prescribed by a clinician registered with the PROMACTACARES program; all ITP patients receiving eltrombopag must be enrolled in the PROMACTACARES program.^{1 7} (See Restricted Distribution under Dosage and Administration.)

  
  


• 
  

  Under the REMS program approved by FDA, medication guide must be dispensed with every prescription for the drug.¹⁰

  
  


• 
  

  Importance of carefully reading patient information (medication guide) provided by the manufacturer before initiating therapy, and each time prescription is refilled.^{1 7}

  
  


• 
  

  Importance of informing patients that risks associated with long-term administration of eltrombopag are not known.¹

  
  


• 
  

  Importance of understanding the goal of therapy is to achieve and maintain a platelet count of ≥50,000/mm ³ to reduce the risk of bleeding, not to normalize platelet count.^{1 7}

  
  


• 
  

  Risk of hepatic failure; importance of immediately reporting symptoms suggestive of jaundice (e.g., yellowing of skin or eyes), unusual darkening of urine, unusual fatigue, or right-upper quadrant (i.e., stomach area) pain to clinician.^{1 7}

  
  


• 
  

  Risk of worsening thrombocytopenia with possible bleeding shortly following discontinuance of eltrombopag, compared with such risks prior to starting therapy; increased risk if receiving concomitant anticoagulant or antiplatelet drugs.^{1 7}

  
  


• 
  

  Risk of reticulin fiber formation in bone marrow with possible progression to bone marrow fibrosis.^{1 7}

  
  


• 
  

  Increased risk of thrombosis or thromboembolism with high platelet counts resulting from excessive eltrombopag dosage.^{1 7} Risk of thrombosis even with normal or low platelet counts.⁷ Importance of immediately reporting symptoms suggestive of thrombosis (e.g., swelling, pain, or tenderness in leg) to clinician.⁷

  
  


• 
  

  Increased risk of developing a hematologic malignancy, especially in patients with myelodysplastic syndrome (MDS).^{1 7}

  
  


• 
  

  Importance of avoiding situations or medications that may increase risk of bleeding.^{1 7}

  
  


• 
  

  Risk of new or worsened cataracts.^{1 7}

  
  


• 
  

  Importance of taking eltrombopag on an empty stomach (i.e., 1 hour before or 2 hours after a meal). ^{1 7} Importance of avoiding foods, supplements, and drugs that contain polyvalent cations (e.g., iron, calcium, aluminum, magnesium, selenium, zinc) for 4 hours before and after taking eltrombopag.^{1 7}

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.^{1 7}

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{1 7}

  
  


• 
  

  Importance of informing 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.

Distribution of eltrombopag is restricted.¹

Eltrombopag Olamine

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablet	25 mg (of eltrombopag)	Promacta	GlaxoSmithKline
		50 mg (of eltrombopag)	Promacta	GlaxoSmithKline
		75 mg (of eltrombopag)	Promacta	GlaxoSmithKline

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 October 27, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. GlaxoSmithKline. Promacta (eltrombopag) tablets prescribing information. Research Triangle Park, NC; 2009 Oct.

2. Bussel JB, Cheng G, Saleh MN et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med. 2007; 357:2237-47. [PubMed 18046028]

3. Bussel JB, Provan D, Shamsi T et al. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial. Lancet. 2009; 373:641-8. [PubMed 19231632]

4. Williams DD, Peng B, Bailey CK et al. Effects of food and antacids on the pharmacokinetics of eltrombopag in healthy adult subjects: Two single-dose, open-label, randomized-sequence, crossover studies. Clin Ther. 2009; 31:764-76. [PubMed 19446149]

5. Bussel JB, Cheng G, Saleh MN et al. Safety and efficacy of long-term treatment with oral eltrombopag for chronic idiopathic thrombocytopenic purpura. Blood. 2008; 112: Abstract 3420.

6. Fogarty PF, Bussel JB, Cheng G et al. Oral eltrombopag treatment reduces the need for concomitant medications in patients with chronic idiopathic thrombocytopenic purpura. Blood. 2008; 112: Abstract 3424.

7. GlaxoSmithKline. Promacta (eltrombopag) tablets medication guide. Research Triangle Park, NC; 2010 Mar.

8. Food and Drug Administration. Promacta (eltrombopag): portal venous system thromboses in study of patients with chronic liver disease. Rockville, MD; May 12, 2010. From FDA website.

9. Aivado M. Dear healthcare professional letter: Promacta (eltrombopag) notification of safety information: portal venous system thromboses in a study of patients with chronic liver disease (ELEVATE). Collegeville, PA: GlaxoSmithKline; 2010 May 4. From FDA website.

10. GlaxoSmithKline. Promacta (eltrombopag) NDA 22-291 proposed risk evaluation and mitigation strategy (REMS). Collegeville, PA; 2010 Jun 10. Available from FDA website. Accessed 2010 Nov 24.

More Eltrombopag resources

• Eltrombopag Side Effects (in more detail)
• Eltrombopag Dosage
• Eltrombopag Use in Pregnancy & Breastfeeding
• Eltrombopag Drug Interactions
• Eltrombopag Support Group
• 1 Review for Eltrombopag - Add your own review/rating

• Eltrombopag MedFacts Consumer Leaflet (Wolters Kluwer)


• Eltrombopag Professional Patient Advice (Wolters Kluwer)


• eltrombopag Advanced Consumer (Micromedex) - Includes Dosage Information


• Promacta Prescribing Information (FDA)


• Promacta Consumer Overview

Compare Eltrombopag with other medications

• Idiopathic Thrombocytopenic Purpura
• Thrombocytopenia Idiopathic

Estring 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.

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 Estring resources

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

Compare Estring 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

  
  

See also: Estring side effects (in more detail)

Hurricaine

Generic Name: benzocaine (Oral route, Oromucosal route)

BEN-zoe-kane

Commonly used brand name(s)

In the U.S.

• Anbesol


• Babee Teething


• Benzodent


• Benz-O-Sthetic


• Bi-Zets/Benzo-Troches


• Dentemp's


• Dent-O-Kain/20


• Detane


• Gumsol


• HAD


• Hurricaine


• Hurricane Spray Kit


• Kank-A Soft Brush


• Larynex


• Miradyne-3


• Mycinette


• Orabase-B


• Oracaine


• Ora film


• Orajel


• OraMagic Plus


• Orasol


• Red Cross Canker Sore


• Thorets


• Trocaine


• Zetts


• Zilactin


• Zilactin-B

In Canada

• Anbesol Extra Strength


• Anbesol Liquid


• Baby Anbesol


• Baby Orajel


• Baby Orajel Liquid


• Maximum Strength Orajel Pm


• Orajel Extra Strength

Available Dosage Forms:

• Liquid


• Gel/Jelly


• Solution


• Lozenge/Troche


• Film


• Lotion


• Ointment


• Powder for Suspension


• Cream


• Tablet, Disintegrating


• Swab


• Spray


• Gum


• Paste

Therapeutic Class: Anesthetic, Local

Chemical Class: Amino Ester

Uses For Hurricaine

Benzocaine lozenges are used to relieve pain and irritation caused by sore throat, sore mouth, or canker sores.

This medicine is available without a prescription; however, your doctor may have special instructions on the proper use and dose for your medical problem.

Before Using Hurricaine

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

No information is available on the relationship of age to the effects of benzocaine lozenges in the pediatric population. Safety and efficacy have not been established in children below 5 years of age.

Geriatric

No information is available on the relationship of age to the effects of benzocaine in geriatric patients.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Infection in or around your mouth or


• Large sores in or around your mouth—The chance of side effects may be increased.

Proper Use of benzocaine

This section provides information on the proper use of a number of products that contain benzocaine. It may not be specific to Hurricaine. Please read with care.

Use this medicine exactly as directed by your doctor. Do not use more of this medicine, do not use it more often, and do not use it for a longer time than directed. To do so may increase the chance of absorption into the body and the risk of side effects.

This medicine should be used only for problems being treated by your doctor or conditions listed in the package directions. Check with your doctor before using it for other problems, especially if you think that an infection may be present.

Do not use this medicine for more than 2 days without checking first with your doctor.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (lozenges):
  
  • For sore throat and mouth pain:
    
    • Adults, teenagers, and children 5 years of age and older—One lozenge, dissolved slowly in the mouth every 2 hours as needed.
    
    
    • Children younger than 5 years of age—Use is not recommended.
    
    
  
  

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using Hurricaine

If your condition does not improve within 7 days, or if it becomes worse, check with your doctor.

Call your doctor right away if you start to have a severe sore throat or sore throat that occurs with a high fever, headache, nausea, or vomiting. These maybe signs of an infection.

Hurricaine Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

Incidence not known

• Headache


• high fever


• nausea


• vomiting


• worsening of pain, redness, swelling, or irritation in or around the mouth

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also: Hurricaine side effects (in more detail)

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More Hurricaine resources

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

• Hurricaine Concise Consumer Information (Cerner Multum)


• Americaine Ointment MedFacts Consumer Leaflet (Wolters Kluwer)


• Benz-O-Sthetic Gel MedFacts Consumer Leaflet (Wolters Kluwer)


• Lanacane Aerosol Spray MedFacts Consumer Leaflet (Wolters Kluwer)


• OraMagic Plus Suspension MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Hurricaine with other medications

• Oral and Dental Conditions

Estramustine Phosphate Sodium

Class: Antineoplastic Agents
VA Class: AN900
Chemical Name: 3-[bis(2-chloroethyl)carbamate] 17-(dihydrogen phosphate)-estra-1,3,5(10)-triene-3,17-diol (17β) disodium salt
Molecular Formula: C₂₃H₃₀Cl₂NNa₂O₆P
CAS Number: 2998-57-4
Brands: Emcyt

Introduction

Antimicrotubule antineoplastic agent; a complex of 17 β-estradiol and nornitrogen mustard.^{1 2 3 9 13 15}

Uses for Estramustine Phosphate Sodium

Prostate Cancer

Palliative treatment of metastatic and/or progressive prostate cancer.^{1 13}

Considered by many clinicians to be an alternative to conventional measures (e.g., orchiectomy, hormonal therapy); generally used in treatment of hormone-refractory prostate cancer.^{2 4 5 14 15}

Combination therapy with etoposide, paclitaxel, or vinblastine⁹ may result in higher objective response rates and greater improvements in subjective parameters (e.g., pain) for treatment of hormone-refractory disease.^{2 9}

Estramustine Phosphate Sodium Dosage and Administration

General

• 
  

  Consult specialized references for procedures for proper handling and disposal of antineoplastics.

  
  

Administration

Oral Administration

Administer orally 3 or 4 times daily.^{1 13}

Food or calcium-containing products may decrease absorption.^{1 2 13} Administer orally 1 hour before or 2 hours after meals with water; avoid concomitant administration with calcium-containing foods or beverages (e.g., milk, milk products) or drugs (e.g., calcium-containing antacids).^{1 2 13}

Dosage

Available as estramustine phosphate sodium; dosage expressed in terms of estramustine phosphate.¹

Adults

Prostate Cancer

Oral

14 mg/kg (i.e., one 140-mg capsule for each 10 kg or 22 lb of body weight) daily in 3 or 4 divided doses.^{1 13} In clinical studies in the US, most patients received dosages of 10–16 mg/kg daily.^{1 13}

Administer 30–90 days before assessing potential benefits of continuing.^{1 13} Continue therapy as long as response is satisfactory; some patients have received >3 years.¹

Cautions for Estramustine Phosphate Sodium

Contraindications

• 
  

  Known hypersensitivity to estramustine, estradiol (or other estrogens), nitrogen mustard, or any ingredient in the formulation.^{1 15}

  
  


• 
  

  Active thrombophlebitis or thromboembolic disorders, except when such conditions are caused by the tumor mass, and clinician judges that anticipated benefits outweigh potential risks.¹

  
  

Warnings/Precautions

Warnings

Estrogenic Effects

Risk of adverse effects from estrogenic metabolites; consider cautions, precautions, and contraindications associated with estrogens.¹⁵

Risk of breast tenderness¹ and mild or moderate breast enlargement.¹ Gynecomastia^{1 2 3 4 7 10 13} and impotence¹ are known estrogenic effects.¹

Cardiovascular Effects

Risk of thrombotic and thromboembolic disorders,¹³ including thrombophlebitis,^{1 3} AMI,^{1 11} pulmonary embolism,^{1 10 13} cerebrovascular accident,^{1 11} and leg cramps.¹ Use with caution in patients with history of thrombophlebitis, thrombosis, or thromboembolic disorders (especially if associated with estrogen use); caution in patients with cerebrovascular or coronary artery disease.¹

Hypertension⁴ may occur; monitor BP periodically.¹

Endocrine and Metabolic Effects

Risk of decreased glucose tolerance;^{4 15} patients with diabetes mellitus should be carefully monitored.¹

Sensitivity Reactions

Risk of angioedema, rash, and pruritus.¹

Major Toxicities

Cardiovascular Effects

Risk of exacerbation of preexisting or incipient peripheral edema^{1 3 4 8 9} or CHF.^{1 3} Use with caution in patients with conditions that might be aggravated by fluid retention (e.g., CHF, epilepsy, migraine, renal dysfunction), and carefully monitor such patients.^{1 13}

Hepatic Effects

Risk of elevated AST (SGOT), LDH,¹⁵ and/or bilirubin concentrations.^{2 15} Monitor liver function during and for 2 months following discontinuance.¹

GI Effects

Risk of nausea,^{1 2 3 4 6 7 8 9 10 13} diarrhea,^{1 3 4 8 13} and minor GI upset.¹

General Precautions

Fetal/Neonatal Morbidity and Mortality

Estramustine was not mutagenic in the Ames test; however, estradiol and nitrogen mustard are known mutagens.¹ Avoid pregnancy during therapy.¹

Metabolic Effects

Potential influence on metabolism of calcium and phosphorus; use with caution in patients with metabolic bone diseases associated with hypercalcemia or in patients with renal impairment.¹ Risk of hypocalcemia in patients with prostate cancer and osteoblastic metastases; closely monitor calcium concentrations.^a

Specific Populations

Pregnancy

Category X.¹⁵ (See Fetal/Neonatal Morbidity and Mortality under Cautions.) Not intended for use in women.¹⁵

Lactation

Not intended for use in women.¹⁵

Pediatric Use

Safety and efficacy not established; use not recommended in pediatric patients.¹⁵

Geriatric Use

Safety and efficacy not specifically studied to date.¹⁵ Careful monitoring for toxicity recommended.¹⁵

Hepatic Impairment

Decreased metabolism in patients with hepatic impairment; use with caution.¹

Renal Impairment

May influence metabolism of calcium and phosphorus; use with caution.¹

Common Adverse Effects

Nausea, diarrhea, minor GI upset, breast tenderness, breast enlargement, edema, elevated AST [SGOT] and/or LDH concentrations, dyspnea.¹

Interactions for Estramustine Phosphate Sodium

Calcium-containing Foods or Drugs

Potential decreased absorption when administered concomitantly with calcium-containing foods or beverages (e.g., milk, milk products) or drugs (e.g., calcium-containing antacids).^{1 3 13} (See Oral Administration under Dosage and Administration.)

Estramustine Phosphate Sodium Pharmacokinetics

Absorption

Bioavailability

After oral administration, approximately 75% of estramustine phosphate absorbed into GI tract tissues and rapidly dephosphorylated to cytotoxic estramustine, most of which is subsequently oxidized to an active cytotoxic metabolite, estromustine.^{1 2 3 9 13} Relative bioavailability of estromustine is approximately 44%.²

Peak plasma concentrations of estromustine usually are attained within 2–4 hours.^{2 3} Estramustine phosphate not detected in plasma after oral administration.^{2 3 b}

Food

Calcium-containing foods or beverages (e.g., milk, milk products) may decrease absorption.¹

Distribution

Extent

Estramustine and estromustine are distributed into prostatic carcinoma tissues and plasma; the tumor to plasma concentration ratio of estramustine or estromustine is approximately 6 or 1, respectively.³

Elimination

Metabolism

Approximately 10–20% of estramustine or estromustine is metabolized to estradiol or estrone, respectively.^{2 3 9 13} Markedly elevated estradiol concentrations detected as early as 1 week of estramustine phosphate initiation; may persist for 7–12 weeks after discontinuance.¹⁵

Elimination Route

Estramustine, estromustine, and their metabolites excreted principally in bile; <1% of conjugated estradiol and estrone excreted in urine.^{1 3 13 15}

Half-life

After oral administration, mean elimination half-life of estromustine was approximately 10.3 hours.³

Special Populations

Decreased metabolism in patients with hepatic impairment.¹

Stability

Storage

Oral

Capsules

2–8° C.¹

ActionsActions

• 
  

  Estramustine and estromustine bind to tubulin and/or microtubule-associated proteins,^{2 3 9 13 15} resulting in depolymerization of microtubules and, subsequently, cellular metaphase arrest.^{2 3 13}

  
  


• 
  

  May damage cell membrane, promote DNA breakage, interfere with DNA replication, and induce cellular apoptosis in other cell lines (e.g., glioma cells, colon cancer cells).^{2 3 15}

  
  

Advice to Patients

• 
  

  Importance of using effective contraception method during therapy; if pregnancy occurs in the partner of a patient, advise patient and partner of risk to the fetus.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.¹

  
  


• 
  

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

  
  

Preparations

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

Estramustine Phosphate Sodium

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	140 mg (of estramustine phosphate)	Emcyt	Pfizer

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 04/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Emcyt 140MG Capsules (PFIZER U.S.): 150/$892 or 450/$2584.99

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 May 01, 2004. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Pharmacia. Emcyt (estramustine phosphate sodium) capsules prescribing information. Kalamazoo, MI; 1999 Feb.

2. Perry CM, McTavish D. Estramustine phosphate sodium: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in prostate cancer. Drugs Aging. 1995; 7:49-74. [PubMed 7579781]

3. Bergenheim AT and Henriksson R. Pharmacokinetics and pharmacodynamics of estramustine phosphate. Clin Pharmacokinet. 1998; 34:163-72. [PubMed 9515186]

4. Anon. Drug of choice for cancer chemotherapy. Med Lett Drugs Ther. 2000; 42:83-92. [PubMed 10994034]

5. Prostate cancer. From: PDQ Information for Health Care Professionals (database). Bethesda, MD: National Cancer Institute; 2002 Feb. From NCI website.

6. Benson RC, Wear JB, and Gill GM. Treatment of stage D hormone- resistant carcinoma of the prostate with estramustine phosphate. J Urol. 1979; 121:452-4. [IDIS 122742] [PubMed 439216]

7. Mittelman A, Shukla SK, and Murphy GP. Extended therapy of stage D carcinoma of the prostate with oral estramustine phosphate. J Urol. 1976; 115:409-12. [PubMed 1263317]

8. de Kernion JN, Murphy GP, Priore R et al. Comparison of flutamide and Emcyt in hormone- refractory metastatic prostatic cancer. Urology. 1988; 31:312-7. [PubMed 3281365]

9. Hudes G, Einhorn L, Ross E et al. Vinblastine versus vinblastine plus oral estramustine phosphate for patients with hormone-refractory prostate cancer: a Hoosier Oncology Group and Fox Chase Network phase III trial. J Clin Oncol. 1999; 17:3160-6. [IDIS 436791] [PubMed 10506613]

10. Kuhn MW, Weissbach L, and Hinke A for the Prostate Cancer Study Group. Primary therapy of metastatic prostate carcinoma with depot gonadotropin-releasing hormone analogue goserelin versus estramustine phosphate. Urology. 1994; 43(Suppl 2):61-7. [PubMed 8116135]

11. Johansson JE, Andersson SO, Beckman KW et al. Clinical evaluation of flutamide and estramustine as initial treatment of metastatic carcinoma of prostate. Urology. 1987; 29:55-9. [PubMed 3798631]

12. Roessler W, Hinke A, and Wieland WF. Experience in advanced prostatic cancer: orchiectomy and flutamide versus orchiectomy and estramustine phosphate. Urology. 1994; 43(Suppl 2):57-60. [PubMed 8116134]

13. Rowinsky EK and Tolcher AW. Antimicrotubule agents. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: principles and practice of oncology. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2001:431- 52.

14. Carroll PR, Lee KL, Fuks ZY et al. Cancer of the prostate. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: principles and practice of oncology. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2001:1418-79

15. Pharmacia, Kalamazoo, MI: Personal communication.

a. Pharmacia. Emcyt (estramustine phosphate sodium) capsules prescribing information. Kalamazoo, MI; 2003 Mar.

b. Hudes G, Haas N, Yeslow G et al. Phase I clinical and pharmacologic trial of intravenous estramustine phosphate. J Clin Oncol. 2002; 20:1115-27. [IDIS 479067] [PubMed 11844837]

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