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Monday 8 October 2012

Elixophyllin

Generic Name: theophylline (Oral route)

thee-OF-i-lin

Commonly used brand name(s)

In the U.S.

Elixophyllin

Norphyl

Phyllocontin

Quibron-T

Quibron-T/SR

Theo-24

TheoCap

Theochron

Theo-Dur

Theo-Time

Truxophyllin

Uniphyl

Available Dosage Forms:

Solution

Tablet, Extended Release, 12 HR

Tablet

Capsule, Extended Release, 24 HR

Capsule, Extended Release

Tablet, Extended Release

Capsule, Extended Release, 12 HR

Syrup

Capsule

Tablet, Extended Release, 24 HR

Elixir

Tablet, Enteric Coated

Therapeutic Class: Bronchodilator

Chemical Class: Methylxanthine

Uses For Elixophyllin

Theophylline is used together with other medicines to treat the symptoms of asthma, bronchitis, emphysema, and other lung diseases.

Theophylline belongs to a group of medicines known as bronchodilators. Bronchodilators are medicines that relax the muscles in the bronchial tubes (air passages) of the lungs. They relieve cough, wheezing, shortness of breath, and troubled breathing by increasing the flow of air through the bronchial tubes.

This medicine is available only with your doctor's prescription.

Before Using Elixophyllin

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

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of theophylline in children. However, children younger than 1 year of age are more likely to have serious side effects, which may require caution and an adjustment in the dose for patients receiving theophylline.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of theophylline in the elderly. However, elderly patients may be more sensitive to the effects of theophylline than younger adults, and are more likely to have kidney, liver, heart, or lung problems, which may require caution and an adjustment in the dose for patients receiving theophylline.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	C	Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.

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. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Bupropion

Cimetidine

Ciprofloxacin

Deferasirox

Desogestrel

Dienogest

Drospirenone

Enoxacin

Erythromycin

Estradiol Cypionate

Estradiol Valerate

Ethinyl Estradiol

Ethynodiol Diacetate

Etintidine

Etonogestrel

Fluvoxamine

Halothane

Idrocilamide

Imipenem

Levofloxacin

Levonorgestrel

Medroxyprogesterone Acetate

Mestranol

Mexiletine

Norelgestromin

Norethindrone

Norgestimate

Norgestrel

Pefloxacin

Peginterferon Alfa-2a

Rofecoxib

Thiabendazole

Troleandomycin

Vemurafenib

Zileuton

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Adenosine

Adinazolam

Alprazolam

Aminoglutethimide

Amiodarone

Azithromycin

Bromazepam

Brotizolam

Cannabis

Carbamazepine

Chlordiazepoxide

Clobazam

Clonazepam

Clorazepate

Diazepam

Disulfiram

Estazolam

Febuxostat

Flunitrazepam

Flurazepam

Fosphenytoin

Halazepam

Interferon Alfa-2a

Ipriflavone

Isoproterenol

Ketazolam

Lorazepam

Lormetazepam

Medazepam

Methotrexate

Midazolam

Nilutamide

Nitrazepam

Oxazepam

Pancuronium

Pentoxifylline

Phenobarbital

Phenytoin

Piperine

Prazepam

Propafenone

Quazepam

Rifampin

Rifapentine

Riluzole

Ritonavir

Secobarbital

St John's Wort

Tacrine

Tacrolimus

Telithromycin

Temazepam

Ticlopidine

Triazolam

Viloxazine

Zafirlukast

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. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

Caffeine

food

Proper Use of theophylline

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

Take this medicine exactly as directed by your doctor. Do not take more of it and do not take it more often than your doctor ordered. This medicine works best if there is a constant amount in the blood. To keep the blood level constant, take this medicine at the same time each day and do not miss any doses.

After you or your child begin taking theophylline, it is very important that your doctor check the level of the medicine in the blood at regular intervals to decide if the dose needs to be changed. Keep all appointments for testing the blood level.

Take the extended-release capsule or tablet every morning at the same time each day. You may take your second dose 10 to 12 hours after the morning dose and before the evening meal, unless your doctor tells you otherwise.

Swallow the extended-release tablet whole. Do not break, crush, or chew it. You may take the extended-release tablet with or without food.

It is best to take the extended-release capsule one hour before a high-fat meal or without food.

Measure the oral liquid with a marked measuring spoon, oral syringe, or medicine cup. The average household teaspoon may not hold the right amount of liquid.

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.

To treat symptoms of asthma, bronchitis, and emphysema:
- For oral dosage form (elixir or tablets):
  - Adults, teenagers, and children above 1 year of age weighing more than 45 kilograms (kg)—At first, 300 milligrams (mg) per day, divided and given every 6 to 8 hours. Your doctor may adjust your dose as needed. However, the total dose is usually not more than 600 mg per day.
  - Older adults—The dose must be determined by your doctor. However, the total dose is usually not more than 400 milligrams per day, divided and given every 6 to 8 hours.
  - Children and teenagers 1 to 15 years of age weighing less than 45 kilograms (kg)—Dose is based on body weight and must be determined by your doctor. At first, the dose is 12 to 14 milligrams (mg) per kg of body weight per day, divided and given every 4 to 6 hours. Your doctor may adjust your dose as needed. However, the total dose is usually not more than 20 mg per kg of body weight per day or 600 mg per day.
  - Infants younger than 1 year of age—Dose is based on body weight and age and must be determined by your doctor.
- For oral dosage form (extended-release capsules):
  - Adults, teenagers, and children 12 years of age and older weighing more than 45 kilograms (kg)—At first, 300 to 400 milligrams (mg) as a single dose, usually in the morning, or divided and given two times per day. Your doctor may adjust your dose as needed. However, the total dose is usually not more than 600 mg per day.
  - Older adults—The dose must be determined by your doctor. However, the total dose is usually not more than 400 milligrams per day as a single dose, usually in the morning, or divided and given two times per day.
  - Children and teenagers 12 to 15 years of age weighing less than 45 kilograms (kg)—Dose is based on body weight and must be determined by your doctor. At first, the dose is 12 to 14 milligrams (mg) per kg of body weight per day as a single dose, usually in the morning, or divided and given two times per day. Your doctor may adjust your dose as needed. However, the total dose is usually not more than 20 mg per kg of body weight per day or 600 mg per day.
  - Children younger than 12 years of age—Use and dose must be determined by your doctor.
- For oral dosage form (extended-release tablets):
  - Adults, teenagers, and children 6 years of age and older weighing more than 45 kilograms (kg)—At first, 300 milligrams (mg) per day, divided and given every 12 hours. Your doctor may adjust your dose as needed. However, the total dose is usually not more than 600 mg per day.
  - Older adults—The dose must be determined by your doctor. However, the total dose is usually not more than 400 milligrams per day, divided and given every 12 hours.
  - Children and teenagers 6 to 15 years of age weighing less than 45 kilograms (kg)—Dose is based on body weight and must be determined by your doctor. At first, the dose is 12 to 14 milligrams (mg) per kg of body weight per day, divided and given every 12 hours. Your doctor may adjust your dose as needed. However, the total dose is usually not more than 20 mg per kg of body weight per day or 600 mg per day.
  - Children younger than 6 years of age—Use and dose must be determined by your doctor.

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 Elixophyllin

It is very important that your doctor check the progress of you or your child at regular visits, especially for the first few weeks after you begin using this medicine. Blood tests may be needed to check for unwanted effects.

A change in your usual behavior or physical well-being may affect the way this medicine works in your body. Tell your doctor if you or your child:

Have had a fever of 102 degrees F or higher for at least 24 hours or more.

Have started or stopped smoking tobacco or marijuana in the last few weeks.

Have started or stopped taking another medicine in the last few weeks.

Have changed your diet in the last few weeks.

Stop using this medicine and check with your doctor right away if you or your child have the following symptoms while using this medicine: nausea or vomiting that continues, headaches, trouble with sleeping, seizures, or irregular heartbeats.

Do not stop or change the dose of this medicine without checking first with your doctor.

Before you have any medical tests, tell the medical doctor in charge that you or your child are using this medicine. The results of some tests may be affected by this medicine.

This medicine may add to the central nervous system (CNS) stimulant effects of caffeine-containing foods or beverages such as chocolate, cocoa, tea, coffee, and cola drinks. Avoid eating or drinking large amounts of these foods or beverages while using this medicine. If you have questions about this, check with your doctor.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines for appetite control, asthma, colds, cough, hay fever, or sinus problems, and herbal (e.g., St. John's wort) or vitamin supplements.

Elixophyllin 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

Chest pain or discomfort

dizziness

fainting

fast, slow, or irregular heartbeat

increase in urine volume

lightheadedness

persistent vomiting

pounding or rapid pulse

seizures

shakiness

Get emergency help immediately if any of the following symptoms of overdose occur:

Symptoms of overdose

Abdominal or stomach pain

blurred vision

confusion

confusion about identity, place, and time

dark-colored urine

decrease in frequency of urination

decreased urine

diarrhea

difficulty in passing urine (dribbling)

dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position

dry mouth

fast, pounding, or irregular heartbeat or pulse

fever

increased thirst

irregular heartbeat

loss of appetite

mood changes

muscle cramps or spasms

muscle pain or stiffness

nausea or vomiting

nervousness

numbness or tingling in the hands, feet, or lips

pain or discomfort in the arms, jaw, back, or neck

painful urination

shakiness in the legs, arms, hands, or feet

shortness of breath

sweating

unusual tiredness or weakness

vomiting of blood or material that looks like coffee grounds

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Incidence not known

Headache

irritability

restlessness

sleeplessness

trouble sleeping

unable to sleep

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: Elixophyllin 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 Elixophyllin resources

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

Elixophyllin Prescribing Information (FDA)

Elixophyllin Concise Consumer Information (Cerner Multum)

Elixophyllin Elixir MedFacts Consumer Leaflet (Wolters Kluwer)

Theophylline Prescribing Information (FDA)

Theophylline Professional Patient Advice (Wolters Kluwer)

Quibron-T MedFacts Consumer Leaflet (Wolters Kluwer)

Quibron-T Prescribing Information (FDA)

Theo-24 Prescribing Information (FDA)

TheoCap Sustained-Release Capsules MedFacts Consumer Leaflet (Wolters Kluwer)

Theochron Sustained-Release Tablets MedFacts Consumer Leaflet (Wolters Kluwer)

Theolair tablets Prescribing Information (FDA)

Theophyllines Monograph (AHFS DI)

Uniphyl Prescribing Information (FDA)

Compare Elixophyllin with other medications

Apnea of Prematurity
Asthma, acute
Asthma, Maintenance

Sunday 7 October 2012

Emcyt

Generic Name: 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

Introduction

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

Uses for Emcyt

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

Emcyt 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 Emcyt

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 Gynecomastia¹ 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 edema¹ 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 Emcyt

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.)

Emcyt 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]

More Emcyt resources

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

Emcyt Prescribing Information (FDA)

Emcyt Concise Consumer Information (Cerner Multum)

Emcyt Advanced Consumer (Micromedex) - Includes Dosage Information

Emcyt MedFacts Consumer Leaflet (Wolters Kluwer)

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Prostate Cancer

Thursday 4 October 2012

Elocon

Generic Name: mometasone (Topical application route)

moe-MET-a-sone FURE-oh-ate

Commonly used brand name(s)

In the U.S.

Elocon

In Canada

Elocom

Pms-Mometasone

Available Dosage Forms:

Ointment

Lotion

Cream

Solution

Therapeutic Class: Corticosteroid, Strong

Pharmacologic Class: Mometasone

Uses For Elocon

Mometasone topical is used to help relieve redness, itching, swelling, or other discomfort caused by skin conditions. This medicine is a corticosteroid (cortisone-like medicine or steroid).

This medicine is available only with your doctor's prescription.

Before Using Elocon

Allergies

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of mometasone topical cream and ointment in children 2 years of age and older, and topical lotion in children 12 years of age and older. However, because of this medicine's toxicity, it should be used with caution. Children may absorb large amounts through the skin, which can cause serious side effects. If your child is using this medicine, follow your doctor's instructions very carefully. Use of the topical cream and ointment in children younger than 2 years of age, and the topical lotion in children younger than 12 years of age, is not recommended.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of mometasone topical in the elderly.

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.

Proper Use of mometasone

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

It is very important that you use this medicine only as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered. To do so may cause unwanted side effects or skin irritation.

This medicine is for use on the skin only. Do not get it in your eyes. Do not use it on skin areas that have cuts, scrapes, or burns. If it does get on these areas, rinse it off right away with water.

This medicine should only be used for skin conditions that your doctor is treating. Check with your doctor before using it for other conditions, especially if you think that a skin infection may be present. This medicine should not be used to treat certain kinds of skin infections or conditions, such as severe burns.

Do not use this medicine on the face, groin, or underarms unless directed to do so by your doctor.

Do not use this medicine in the diaper area of an infant. Diapers or plastic pants will increase the amount of medicine absorbed through the skin and cause unwanted side effects.

To use:

Wash your hands with soap and water before and after using this medicine.

Apply a thin layer of this medicine to the affected area of the skin. Rub it in gently.

Do not bandage or otherwise wrap the skin being treated unless directed to do so by your doctor.

If your doctor ordered an occlusive dressing or airtight covering to be applied over the medicine, make sure you know how to apply it. Occlusive dressings increase the amount of medicine absorbed through your skin, so use them only as directed. If you have any questions about this, check with your doctor.

Dosing

For redness, itching, and swelling of the skin:
- For topical dosage forms (cream and ointment):
  - Adults—Apply to the affected area of the skin once per day.
  - Children 2 years of age and older—Apply to the affected area of the skin once per day.
  - Children younger than 2 years of age—Use is not recommended.
- For topical dosage form (lotion):
  - Adults—Apply to the affected area of the skin once per day.
  - Children 12 years of age and older—Apply to the affected area of the skin once per day.
  - Children younger than 12 years of age—Use is not recommended.

Missed Dose

If you miss a dose of this medicine, apply 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.

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 Elocon

It is very important that your doctor check the progress of you or your child at regular visits for any unwanted effects that may be caused by this medicine.

If your or your child's symptoms do not improve within two weeks, or if they become worse, check with your doctor.

Using too much of this medicine or using it for a long time may increase your risk of having adrenal gland problems. The risk is greater for children and patients who use large amounts for a long time. Talk to your doctor right away if you or your child have more than one of these symptoms while you are using this medicine: blurred vision; dizziness or fainting; a fast, irregular, or pounding heartbeat; increased thirst or urination; irritability; or unusual tiredness or weakness.

Stop using this medicine and check with your doctor right away if you or your child have a skin rash, burning, stinging, swelling, or irritation on the skin.

Do not use cosmetics or other skin care products on the treated areas.

Elocon 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:

Less common

Burning

itching

thinning of the skin with easy bruising, especially when used on the face or where the skin folds together (e.g. between the fingers)

Incidence not known

Dryness

irritation

redness and scaling around the mouth

Less common

Acne or pimples

burning, itching, and pain in hairy areas, or pus at the root of the hair

dry mouth

loss of elasticity

loss of normal skin markings

raised, dark red, and wart-like spots on the skin, especially when used on the face

shininess

Incidence not known

Burning and itching of the skin with pinhead-sized red blisters

increased hair growth on the forehead, back, arms, and legs

lightening of normal skin color

lightening of treated areas of dark skin

reddish purple lines on the arms, face, legs, trunk, or groin

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: Elocon side effects (in more detail)

More Elocon resources

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

Elocon Prescribing Information (FDA)

Elocon topical Monograph (AHFS DI)

Elocon Cream MedFacts Consumer Leaflet (Wolters Kluwer)

Elocon Consumer Overview

Compare Elocon with other medications

Atopic Dermatitis
Dermatitis
Eczema
Psoriasis

Wednesday 3 October 2012

Boots Skin Therapy Emollient Cream 60g

Boots Skin Therapy Emollient Cream

(Almond Oil, Lanolin)

Effective relief for dry skin conditions

Soothes

Moisturisers

Relieves

relieves dry skin conditions such as dry eczema, chapping, nappy soreness and sunburn

60 g e

Read all of this carton for full instructions.

What this medicine is for

An emollient cream that relieves dry skin conditions such as dry eczema, chapping, nappy soreness and sunburn.

Before you use this medicine

X Do not use:

If you are allergic to any of the ingredients

You can use this medicine if you are pregnant or breastfeeding.

Information about some of the ingredients: Cetyl alcohol may cause skin reactions (e.g. contact dermatitis).

How to use this medicine

Check the tube seal is not broken before first use. If it is, do not use the cream. Pierce tube seal with end of cap.

Apply to the skin only.

Adults and children: Use on the affected area 2 or 3 times a day.

If symptoms do not go away talk to your pharmacist or doctor.

If anyone accidentally swallows some: Talk to a pharmacist or doctor.

Possible side effects

Most people will not have problems.

If you get these side effects stop using the cream and see a doctor:

Allergic reaction (e.g. skin rash, red or itchy skin)

If you notice any side effect not listed here, please tell your pharmacist or doctor.

Keep all medicines out of the sight and reach of children.

Use by the date on the end flap of the carton.

Skin Therapy Emollient Cream is a rich, soothing cream to relieve a wide variety of dry skin conditions such as dry eczema, chapping caused by weather or water, nappy soreness and sunburn. It is non perfumed and non-greasy.

Active ingredients

This cream contains Almond Oil 5% w/w, Anhydrous Hypoallergenic Lanolin 1% w/w.

Also contains: purified water, cetyl alcohol, white soft paraffin, cetomacrogol 1000, benzyl alcohol, sorbitan sesquioleate, sodium citrate, anhydrous citric acid.

PL 00014/0369

Text prepared 8/06

Manufactured by the Marketing Authorisation holder

The Boots Company PLC

Nottingham

NG2 3AA

If you need more advice ask your pharmacist.

BTC18977 vA 19-06-07

Tuesday 2 October 2012

Zomig 5mg Nasal Spray

1. Name Of The Medicinal Product

Zomig 5 mg Nasal Spray.

2. Qualitative And Quantitative Composition

Zomig Nasal Spray is an aqueous solution containing 50 mg/ml zolmitriptan, buffered to pH 5.0. The device delivers a unit dose of 5 mg and is intended for a single use only.

For excipients see 6.1.

3. Pharmaceutical Form

Nasal Spray.

4. Clinical Particulars

4.1 Therapeutic Indications

Zomig is indicated for the acute treatment of migraine with or without aura.

4.2 Posology And Method Of Administration

The recommended dose of Zomig Nasal Spray to treat a migraine attack is 5 mg.

Zomig Nasal Spray is administered as a single dose into one nostril. Zomig Nasal Spray provides particularly rapid onset of relief of migraine with the first signs of efficacy apparent within 15 minutes of dosing.

Zomig Nasal Spray provides an alternative non–oral formulation of zolmitriptan to that of Zomig oral tablets and orodispersible tablets. This formulation may also be beneficial where a non–oral route of treatment is either needed or preferred.

If symptoms persist or return within 24 hours a second dose has been shown to be effective. If a second dose is required, it should not be taken within 2 hours of the initial dose.

Zomig is effective whenever the nasal spray is administered during a migraine attack; although it is advisable that Zomig Nasal Spray is taken as early as possible after the onset of migraine headache.

In the event of recurrent attacks, it is recommended that the total intake of Zomig in a 24 hour period should not exceed 10 mg.

Zomig is not indicated for prophylaxis of migraine.

Use in children (under 12 years of age)

Safety and efficacy of Zomig Nasal Spray in paediatric patients have not been evaluated. Use of Zomig Nasal Spray in children is therefore not recommended.

Adolescents (12-17 years of age)

Safety and efficacy of Zomig Nasal Spray in adolescents have not been evaluated. Use of Zomig Nasal Spray in adolescents is therefore not recommended.

Use in Patients Aged Over 65 years

Safety and efficacy of Zomig in individuals aged over 65 years have not been systematically evaluated.

Patients with Hepatic Impairment

The effect of hepatic disease on the pharmacokinetics of zolmitriptan nasal spray has not been evaluated. However, for patients with moderate or severe hepatic impairment metabolism after oral dosing is reduced and a maximum dose of 5 mg oral zolmitriptan in 24 hours is recommended (see Section 5.2 Pharmacokinetic Properties).

Patients with Renal Impairment

No dosage adjustment required (see Section 5.2 Pharmacokinetic Properties).

4.3 Contraindications

Zomig is contraindicated in patients with:

− known hypersensitivity to any component of the product

− uncontrolled hypertension

− ischaemic heart disease

− coronary vasospasm/Prinzmetal's angina

− A history of cerebrovascular accident (CVA) or transient ischaemic attack (TIA)

− Concomitant administration of Zomig with ergotamine or ergotamine derivatives or other 5-HT₁ receptor agonists.

4.4 Special Warnings And Precautions For Use

Zomig should only be used where a clear diagnosis of migraine has been established. Care should be taken to exclude other potentially serious neurological conditions. There are no data on the use of Zomig in hemiplegic or basilar migraine. Migraneurs may be at risk of certain cerebrovascular events. Cerebral haemorrhage, subarachnoid haemorrhage, stroke, and other cerebrovascular events have been reported in patients treated with 5HT_1B/1D agonists.

Zomig should not be given to patients with symptomatic Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathways.

In very rare cases, as with other 5HT_1B/1D agonists, coronary vasospasm, angina pectoris and myocardial infarction have been reported. In patients with risk factors for ischaemic heart disease, cardiovascular evaluation prior to commencement of treatment with this class of compounds, including Zomig, is recommended (see Section 4.3 Contraindications). These evaluations, however, may not identify every patient who has cardiac disease, and in very rare cases, serious cardiac events have occurred in patients without underlying cardiovascular disease.

As with other 5HT_1B/1D agonists, atypical sensations over the precordium (see Section 4.8 Undesirable Effects) have been reported after the administration of zolmitriptan.

If chest pain or symptoms consistent with ischaemic heart disease occur, no further doses of zolmitriptan should be taken until after appropriate medical evaluation has been carried out.

As with other 5HT _1B/1D agonists transient increases in systemic blood pressure have been reported in patients with and without a history of hypertension; very rarely these increases in blood pressure have been associated with significant clinical events.

As with other 5HT _1B/1D agonists, there have been rare reports of anaphylaxis/anaphylactoid reactions in patients receiving Zomig.

Excessive use of an acute anti-migraine medicinal product may lead to an increased frequency of headache, potentially requiring withdrawal of treatment.

Serotonin Syndrome has been reported with combined use of triptans, and Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin Norepinephrine Reuptake Inhibitors (SNRIs). Serotonin Syndrome is a potentially life-threatening condition, and it may include signs and symptoms such as: mental status changes (e.g. agitation, hallucinations, coma), autonomic instability, (e.g. tachycardia, labile blood-pressure, hyperthermia), neuromuscular aberrations (e.g. hyperreflexia, in-coordination), and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea). Careful observation of the patient is advised, if concomitant treatment with Zomig and an SSRI or SNRI is clinically warranted, particularly during treatment initiation and dosage increases (See section 4.5).

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

From studies using oral zolmitriptan tablets, there is no evidence that concomitant use of migraine prophylactic medications has any effect on the efficacy or unwanted effects of Zomig (for example beta-blockers, oral dihydroergotamine, pizotifen).

The pharmacokinetics and tolerability of Zomig oral tablets were unaffected by acute symptomatic treatments such as paracetamol, metoclopramide and ergotamine.

Concomitant administration of other 5HT_1B/1D agonists within 24 hours of Zomig treatment should be avoided.

Data from healthy subjects suggest that there are no pharmacokinetic or clinically significant interactions between Zomig and ergotamine, however, the increased risk of coronary vasospasm is a theoretical possibility. Therefore, it is advised to wait at least 24 hours following the use of ergotamine containing preparations before administering Zomig. Conversely it is advised to wait at least six hours following use of Zomig before administering any ergotamine preparation (see Section 4.3 Contraindications).

Following co-administration of moclobemide, a specific MAO-A inhibitor, and Zomig oral tablets, there was a small increase (26%) in AUC for zolmitriptan and a 3-fold increase in AUC of the active metabolite. Therefore, a maximum intake of 5 mg Zomig nasal spray in 24 hours is recommended in patients taking an MAO-A inhibitor.

Following the co-administration of cimetidine, a general P450 inhibitor, and Zomig oral tablets, the half-life of zolmitriptan was increased by 44% and the AUC increased by 48%. In addition the half-life and AUC of the active N-desmethylated metabolite (183C91) were doubled. A maximum dose of 5 mg Zomig Nasal Spray in 24 hours is recommended in patients taking cimetidine. Based on the overall interaction profile, an interaction with inhibitors of the cytochrome P450 isoenzyme CYP1A2 cannot be excluded. Therefore, the same dosage reduction is recommended with compounds of this type, such as fluvoxamine and the quinolone antibiotics (e.g. ciprofloxacin).

Fluoxetine did not affect the pharmacokinetic parameters of zolmitriptan in a study using oral zolmitriptan tablets. Therapeutic doses of the specific serotonin reuptake inhibitors, fluoxetine, sertraline, paroxetine and citalopram do not inhibit CYP1A2. However, Serotonin Syndrome has been reported during combined use of triptans, and SSRIs (e.g. fluoxetine, paroxetine, sertraline) and SNRIs (e.g. venlafaxine, duloxetine) (See section 4.4).

As with other 5HT_1b/1d agonists, there is the potential for dynamic interactions with the herbal remedy St John's wort (Hypericum perforatum) which may result in an increase in undesirable effects.

The absorption and pharmacokinetics of Zomig Nasal Spray is unaltered by prior administration of the sympathomimetic vasoconstrictor, xylometazoline.

4.6 Pregnancy And Lactation

Pregnancy

Zomig should be used in pregnancy only if the benefits to the mother justify potential risk to the foetus. There are no studies in pregnant women, but there is no evidence of teratogenicity in animal studies. (See Section 5.3 Preclinical Safety Data).

Lactation

Studies have shown that zolmitriptan passes into the milk of lactating animals. No data exist for passage of zolmitriptan into human breast milk. Therefore, caution should be exercised when administering Zomig to women who are breast-feeding.

4.7 Effects On Ability To Drive And Use Machines

There was no significant impairment of performance of psychomotor tests with doses up to 20 mg oral Zomig. Use is unlikely to result in an impairment of the ability of patients to drive or operate machinery. However it should be taken into account that somnolence may occur.

4.8 Undesirable Effects

Zomig is well tolerated. Adverse reactions are typically mild/moderate, transient, not serious and resolve spontaneously without additional treatment.

Possible adverse reactions tend to occur within 4 hours of dosing and are no more frequent following repeated dosing.

The following definitions apply to the incidence of the undesirable effects:

Very common (

The following undesirable effects have been reported following administration with zolmitriptan:

Table 1 Table of Adverse Drug Reactions

System Organ Class	Frequency	Undesirable Effect
Immune system disorders	Rare	Anaphylaxis/Anaphylactoid Reactions; Hypersensitivity reactions
Nervous system disorder	Very common	Taste disturbance
Common	Abnormalities or disturbances of sensation; Dizziness; Headache; Hyperaesthesia; Paraesthesia; Somnolence; Warm sensation
Cardiac disorders	Common	Palpitations
Uncommon	Tachycardia
Very rare	Angina pectoris; Coronary vasospasm; Myocardial infarction
Vascular disorders	Uncommon	Transient increases in systemic blood pressure
Respiratory system disorders	Common	Epistaxis Discomfort of nasal cavity
Gastrointestinal disorders	Common	Abdominal pain; Dry mouth; Nausea; Vomiting
	Very rare	Bloody diarrhoea; Gastrointestinal infarction or necrosis; Gastrointestinal ischaemic events; Ischaemic colitis; Splenic infarction
Skin and subcutaneous tissue disorders	Rare	Angioedema; Urticaria
Musculoskeletal and connective tissue disorders	Common	Muscle weakness; Myalgia
Renal and urinary disorders	Uncommon	Polyuria; Increased urinary frequency
Very rare	Urinary urgency
General disorders	Common	Asthenia; Heaviness, tightness, pain or pressure in throat, neck, limbs or chest

4.9 Overdose

There has been no experience of overdose with zolmitriptan nasal spray. Volunteers receiving single oral doses of 50 mg commonly experienced sedation.

The elimination half-life of zolmitriptan following intranasal administration is 3 hours, (see Section 5.2 Pharmacokinetic Properties) and therefore monitoring of patients after overdose with Zomig Nasal Spray should continue for at least 15 hours or while symptoms or signs persist.

There is no specific antidote to zolmitriptan. In cases of severe intoxication, intensive care procedures are recommended, including establishing and maintaining a patent airway, ensuring adequate oxygenation and ventilation, and monitoring and support of the cardiovascular system.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Selective serotonin (5HT₁) agonists.

ATC code: N02CC03

In pre-clinical studies, zolmitriptan has been demonstrated to be a selective agonist for the vascular human recombinant 5HT_1B and 5HT_1D receptor subtypes. Zolmitriptan is a high affinity 5HT_1B/1D receptor agonist with modest affinity for 5HT_1A receptors. Zolmitriptan has no significant affinity (as measured by radioligand binding assays) or pharmacological activity at 5HT₂-, 5HT₃-, 5HT₄-, alpha₁-, alpha₂-, or beta₁-, adrenergic; H₁-, H₂-, histaminic; muscarinic; dopaminergic₁, or dopaminergic₂ receptors.

The 5HT_1B/1D receptor is predominantly located presynaptically at both the peripheral and central synapses of the trigeminal nerve and preclinical studies have shown that zolmitriptan is able to act at both these sites.

One controlled clinical trial in 696 adolescents with migraine failed to demonstrate superiority of zolmitriptan tablets at doses of 2.5 mg, 5 mg and 10 mg over placebo. Efficacy was not demonstrated.

5.2 Pharmacokinetic Properties

Zolmitriptan, following intranasal administration, is rapidly absorbed with detectable levels in the plasma within 5 minutes of dosing. A proportion of the dose seems to be directly absorbed in the naso-pharynx. On average 40% of C_max of the parent compound, zolmitriptan, is achieved within 15 minutes. The appearance in plasma of the active metabolite, 183C91, which is partly formed through first-pass metabolism, is delayed by 15 to 60 minutes post-dose. C_max of the parent compound, zolmitriptan is achieved after 3 hours. Plasma concentrations are sustained for up to 4 to 6 hours. Elimination of zolmitriptan and the active metabolite 183C91 after oral and intranasal delivery appear similar; the mean elimination half-life (t½) for both zolmitriptan and 183C91 are approximately 3 hours. The bioavailability of intranasal relative to oral administration is 102%. In healthy volunteers after single and multiple intranasal doses, zolmitriptan and its active metabolite 183C91 display dose proportional AUC and C_max over the range 1 to 5 mg. There is no evidence of accumulation of zolmitriptan after multiple intranasal dosing.

The plasma concentrations and elimination pharmacokinetics of zolmitriptan and the three major metabolites for the nasal spray and conventional tablet formulations are similar.

Following oral administration of Zomig conventional tablets, zolmitriptan is rapidly and well absorbed (at least 64%). The mean absolute bioavailability of the parent compound is approximately 40%.

Absorption is rapid with 75% of C_max achieved within 1 hour and plasma concentrations are sustained subsequently for 4 to 6 hours. After oral administration zolmitriptan absorption is unaffected by the presence of food.

Zolmitriptan is eliminated largely by hepatic biotransformation followed by urinary excretion of the metabolites. There are three major metabolites: the indole acetic acid, (the major metabolite in plasma and urine), the N-oxide and N-desmethyl analogues. The N-desmethyl metabolite (183C91) is an active metabolite which is also a 5H _1B/1D agonist and is 2 to 6 times as potent, in animal models, as zolmitriptan. Plasma concentrations of 183C91 are approximately half those of the parent drug, hence it would therefore be expected to contribute to the therapeutic action of Zomig. Over 60% of a single oral dose is excreted in the urine (mainly as the indole acetic acid metabolite) and about 30% in faeces, mainly as unchanged parent compound.

A study using oral zolmitriptan to evaluate the effect of liver disease on the pharmacokinetics of zolmitriptan showed that the AUC and C_max were increased by 94% and 50% respectively in patients with moderate liver disease and by 226% and 47% in patients with severe liver disease compared with healthy volunteers. Exposure to the metabolites, including the active metabolite, was decreased. For the 183C91 metabolite, AUC and C_max were reduced by 33% and 44% in patients with moderate liver disease and by 82% and 90% in patients with severe liver disease.

The plasma half-life (T½) of zolmitriptan was 4.7 hours in healthy volunteers, 7.3 hours in patients with moderate liver disease and 12 hours in those with severe liver disease. The corresponding T½ values for the 183C91 metabolite were 5.7 hours, 7.5 hours and 7.8 hours respectively. No studies have been undertaken to characterise the pharmacokinetics of intranasally administered zolmitriptan in patients with hepatic impairment.

Following intravenous administration, the mean total plasma clearance is approximately 10 ml/min/kg, of which one third is renal clearance. Renal clearance is greater than glomerular filtration rate suggesting renal tubular secretion. The volume of distribution following intravenous administration is 2.4 L/kg. Plasma protein binding is low (approximately 25%). The mean elimination half-life of zolmitriptan is 2.5 to 3 hours. The half-lives of its metabolites are similar, suggesting their elimination is formation-rate limited.

Renal clearance of zolmitriptan and all its metabolites is reduced (7 to 8 fold) in patients with moderate to severe renal impairment compared to healthy subjects, although the AUC of the parent compound and the active metabolite were only slightly higher (16 and 35% respectively) with a 1 hour increase in half-life to 3 to 3.5 hours. These parameters are within the ranges seen in healthy volunteers. These findings originate from studies with zolmitriptan tablets.

In a small group of healthy individuals there was no pharmacokinetic interaction with ergotamine. Concomitant administration of Zomig with ergotamine/caffeine was well tolerated and did not result in any increase in adverse events or blood pressure changes as compared with Zomig alone (see section 4.5 for precautions regarding ergotamine use). These findings originate from studies with zolmitriptan tablets.

Selegiline, an MAO-B inhibitor, and fluoxetine (a selective serotonin reuptake inhibitor; SSRI) had no effect on the pharmacokinetic parameters of zolmitriptan (see section 4.4 for warnings and precautions regarding concomitant use with SSRIs). These findings originate from studies with zolmitriptan tablets.

Following the administration of rifampicin, no clinically relevant differences in the pharmacokinetics of zolmitriptan or its active metabolite were observed. The findings originate from studies with zolmitriptan tablets.

The pharmacokinetics of zolmitriptan in healthy elderly subjects were similar to those in healthy young volunteers. These findings originate from studies with zolmitriptan tablets.

The absorption of zolmitriptan nasal spray in healthy volunteers was found unaltered when administered concomitantly with the sympathomimetic nasal decongestant, xylometazoline.

5.3 Preclinical Safety Data

An oral teratology study of Zomig has been conducted. At the maximum tolerated doses of Zomig, 1200 mg/kg/day (AUC 605 μg/ml.h : approx. 3700 x AUC of the human maximum recommended daily intake of 15 mg) and 30 mg/kg/day (AUC 4.9 μg/ml.h : approx. 30 x AUC of the human maximum recommended daily intake of 15 mg) in rats and rabbits, respectively, no signs of teratogenicity were apparent.

A number of genotoxicity tests have been performed. It was concluded that Zomig is not likely to pose any genetic risk in humans.

Carcinogenicity studies in rats and mice were conducted at the highest feasible doses and gave no suggestion of tumorogenicity.

Reproductive studies in male and female rats, at dose levels limited by toxicity, revealed no effect on fertility.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Each Zomig Nasal Spray vial contains the following excipients:

Citric acid

Disodium phosphate

Purified Water

6.2 Incompatibilities

None known.

6.3 Shelf Life

30 months.

6.4 Special Precautions For Storage

Do not store above 25°C.

6.5 Nature And Contents Of Container

Ph Eur Type I glass vials which are closed with chlorobutyl rubber stoppers. The vials are assembled into a unit dose nasal spray device, comprising of a vial holder, an actuation device and a protection cover.

Packs containing 1, 2, or 6 single use devices.

6.6 Special Precautions For Disposal And Other Handling

The protection cover must not be removed until immediately before use. For instructions for use see the patient information leaflet.

7. Marketing Authorisation Holder

AstraZeneca UK Limited

600 Capability Green

Luton

LU1 3LU

8. Marketing Authorisation Number(S)

PL 17901/0095

9. Date Of First Authorisation/Renewal Of The Authorisation

19^th September 2002/ 18^th June 2008

10. Date Of Revision Of The Text

4^th October 2011

Sunday 30 September 2012

Erythromycin and Sulfisoxazole

Dosage Form: granule, for oral suspension
ERYTHROMYCIN ETHYLSUCCINATE AND SULFISOXAZOLE ACETYL FOR ORAL SUSPENSION, USP

Revised MARCH 2007

11001190

Rx only

DESCRIPTION:

Erythromycin ethylsuccinate and sulfisoxazole acetyl, when reconstituted with water as directed on the label, the granules form a white, cherry flavored suspension that provides the equivalent of 200 mg erythromycin activity and the equivalent of 600 mg of sulfisoxazole activity per teaspoonful (5 mL).

Erythromycin is produced by a strain of Saccaropolyspora erythraea and belongs to the macrolide group of antibiotics. It is basic and readily forms salts and esters. Erythromycin ethylsuccinate is the 2’-ethylsuccinyl ester of erythromycin. It is essentially a tasteless form of the antibiotic suitable for oral administration, particularly in suspension dosage forms. The chemical name is erythromycin 2’-(ethylsuccinate). Erythromycin ethylsuccinate has the following structural formula:

C45H75NO16 Molecular Weight: 862.06

Sulfisoxazole acetyl or N1-acetyl sulfisoxazole is an ester of sulfisoxazole. Chemically, sulfisoxazole is N1-(3,4-dimethyl-5-isoxazotyl) sulfanilamide. Sulfisoxazole acetyl has the following structural formula:

C13H15N3O4S Molecular Weight: 309.34

Inactive Ingredients:

Artificial flavor, lactose anhydrous, methylparaben, polysorbate 80, povidone, simethicone, sodium citrate anhydrous and sucrose.

CLINICAL PHARMACOLOGY:

Orally administered erythromycin ethylsuccinate suspensions are readily and reliably absorbed. Erythromycin ethylsuccinate products have demonstrated rapid and consistent absorption in both fasting and nonfasting conditions. However, higher serum concentrations are obtained when these products are given with food. Erythromycin is largely bound to plasma proteins. After absorption, erythromycin diffuses readily into most body fluids. In the absence of meningeal inflammation, low concentrations are normally achieved in the spinal fluid, but the passage of the drug across the blood-brain barrier increases in meningitis. Erythromycin crosses the placental barrier and is excreted in human milk. Erythromycin is not removed by peritoneal dialysis or hemodialysis.

In the presence of normal hepatic function, erythromycin is concentrated in the liver and is excreted in the bile; the effect of hepatic dysfunction on biliary excretion of erythromycin is not known. After oral administration, less than 5% of the administered dose can be recovered in the active form in the urine.

Wide variation in blood levels may result following identical doses of a sulfonamide. Blood levels should be measured in patients receiving these drugs for serious infections. Free sulfonamide blood levels of 50 to 150 mcg/mL may be considered therapeutically effective for most infections, with blood levels of 120 to 150 mcg/mL being optimal for serious infections. The maximum sulfonamide level should be 200 mcg/mL, because adverse reactions occur more frequently above this concentration.

Following oral administration, sulfisoxazole is rapidly and completely absorbed; the small intestine is the major site of absorption, but some of the drug is absorbed from the stomach. Sulfonamides are present in the blood as free, conjugated (acetylated and possibly other forms), and protein-bound forms. The amount present as “free” drug is considered to be the therapeutically active form. Approximately 85% of a dose of sulfisoxazole is bound to plasma proteins, primarily to albumin; 65% to 72% of the unbound portion is in the nonacetylated form.

Maximum plasma concentrations of intact sulfisoxazole following a single 2 g oral dose of sulfisoxazole to healthy adult volunteers ranged from 127 to 211 mcg/mL (mean 169 mcg/mL), and the time of peak plasma concentration ranged from 1 to 4 hours (mean, 2.5 hours). The elimination half-life of sulfisoxazole ranged from 4.6 to 7.8 hours after oral administration. The elimination of sulfisoxazole has been shown to be slower in elderly subjects (63 to 75 years) with diminished renal function (creatine clearance 37 to 68 mL/min).1 After multiple-dose oral administration of 500 mg q.i.d. to healthy volunteers, the average steady-state plasma concentrations of intact sulfisoxazole ranged from 49.9 to 88.8 mcg/mL (mean 63.4 mcg/mL).2

Sulfisoxazole and its acetylated metabolites are excreted primarily by the kidneys through glomerular filtration. Concentrations of sulfisoxazole are considerably higher in the urine than in the blood. The mean urinary recovery following oral administration of sulfisoxazole is 97% within 48 hours; 52% of this is intact drug, and the remainder is the N4-acetylated metabolite.

Sulfisoxazole is distributed only in extracellular body fluids. It is excreted in human milk. It readily crosses the placental barrier. In healthy subjects, cerebrospinal fluid concentrations of sulfisoxazole vary; in patients with meningitis, however, concentrations of free drug in cerebrospinal fluid as high as 94 mcg/mL have been reported.

Microbiology:

This product has been formulated to contain sulfisoxazole for concomitant use with erythromycin.

Erythromycin acts by inhibition of protein synthesis by binding 50 S ribosomal sub-units of susceptible organisms. It does not affect nucleic acid synthesis. Antagonism has been demonstrated in vitro between erythromycin and clindamycin, lincomycin, and chloramphenicol.

The sulfonamides are bacteriostatic agents, and the spectrum of activity is similar for all. Sulfonamides inhibit bacterial synthesis of dihydrofolic acid by preventing the condensation of the pteridine with para-aminobenzoic acid through competitive inhibition of the enzyme dihydropteroate synthetase. Resistant strains have altered dihydropteroate synthetase with reduced affinity for sulfonamides or produce increased quantities of para-aminobenzoic acid.

Susceptibility Testing:

Quantitative methods that require measurement of zone diameter give the most precise estimates of the susceptibility of bacteria to antimicrobial agents. One such standardized single-disc procedure3 has been recommended for use with discs to test susceptibility to Erythromycin and Sulfisoxazole. Interpretation involves correlation of the zone diameters obtained in the disc test with minimal inhibitory concentration (MIC) values for Erythromycin and Sulfisoxazole.

If the standardized procedure of disc susceptibility is used, a 15 mcg erythromycin disc should give a zone diameter of at least 18 mm when tested against an erythromycin-susceptible bacterial strain, and a 250-300 mcg sulfisoxazole disc should give a zone diameter of at least 17 mm when tested against a sulfisoxazole-susceptible bacterial strain.

In vitro sulfonamides susceptibility tests are not always reliable because media containing excessive amounts of thymidine are capable of reversing the inhibitory effect of sulfonamides, which may result in false resistant reports. The tests must be carefully coordinated with bacteriological and clinical responses. When the patient is already taking sulfonamides, follow-up cultures should have aminobenzoic acid added to the isolation media but not to subsequent susceptibility test media.

INDICATIONS AND USAGE:

For treatment of ACUTE OTITIS MEDIA in children that is caused by susceptible strains of Haemophilus influenzae.

CONTRAINDICATIONS:

Erythromycin ethylsuccinate and sulfisoxazole acetyl for oral suspension is contraindicated in the following patient populations:

: Patients with a known hypersensitivity to either of its components, children younger than 2 months, pregnant women at term, and mothers nursing infants less than 2 months of age.

Use in pregnant women at term, in children less than 2 months of age, and in mothers nursing infants less than 2 months of age is contraindicated because sulfonamides may promote kernicterus in the newborn by displacing bilirubin from plasma proteins.

Erythromycin is contraindicated in patients taking terfenadine. (See PRECAUTIONS, Drug Interactions:.)

WARNINGS:

FATALITIES ASSOCIATED WITH THE ADMINISTRATION OF SULFONAMIDES, ALTHOUGH RARE, HAVE OCCURRED DUE TO SEVERE REACTIONS, INCLUDING STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, FULMINANT HEPATIC NECROSIS, AGRANULOCYTOSIS, APLASTIC ANEMIA, AND OTHER BLOOD DYSCRASIAS.

SULFONAMIDES, INCLUDING SULFONAMIDE-CONTAINING PRODUCTS SUCH AS ERYTHROMYCIN ETHYLSUCCINATE AND SULFISOXAZOLE ACETYL FOR ORAL SUSPENSION, SHOULD BE DISCONTINUED AT THE FIRST APPEARANCE OF SKIN RASH OR ANY SIGN OF ADVERSE REACTION. In rare instances, a skin rash may be followed by a more severe reaction, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic necrosis, and serious blood disorders. (See PRECAUTIONS.)

Clinical signs such as sore throat, fever, pallor, rash, purpura, or jaundice may be early indications of serious reactions.

There have been reports of hepatic dysfunction, with or without jaundice, occurring in patients receiving oral erythromycin products.

Cough, shortness of breath, and pulmonary infiltrates are hypersensitivity reactions of the respiratory tract that have been reported in association with sulfonamide treatment.

The sulfonamides should not be used for the treatment of group A beta-hemolytic streptococcal infections. In an established infection, they will not eradicate the streptococcus and, therefore, will not prevent sequelae such as rheumatic fever.

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including erythromycin ethylsuccinate and sulfisoxazole acetyl for oral suspension, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.

Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is one primary cause of “antibiotic-associated colitis”.

After diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against Clostridium difficile colitis.

There have been reports suggesting that erythromycin does not reach the fetus in adequate concentration to prevent congenital syphilis. Infants born to women treated during pregnancy with erythromycin for early syphilis should be treated with an appropriate penicillin regimen.

Rhabdomyolysis with or without renal impairment has been reported in seriously ill patients receiving erythromycin concomitantly with lovastatin. Therefore, patients receiving concomitant lovastatin and erythromycin should be carefully monitored for creatine kinase (CK) and serum transaminase levels. (See package insert for lovastatin.)

PRECAUTIONS:

General:

Erythromycin is principally excreted by the liver. Caution should be exercised when erythromycin is administered to patients with impaired hepatic function. (See CLINICAL PHARMACOLOGY and WARNINGS sections.)

Prolonged or repeated use of erythromycin may result in an overgrowth of nonsusceptible bacteria or fungi. If superinfection occurs, erythromycin should be discontinued and appropriate therapy instituted.

There have been reports that erythromycin may aggravate the weakness of patients with myasthenia gravis.

When indicated, incision and drainage or other surgical procedures should be performed in conjunction with antibiotic therapy.

Sulfonamides should be given with caution to patients with impaired renal or hepatic function and to those with severe allergy or bronchial asthma. In glucose-6-phosphate dehydrogenase-deficient individuals, hemolysis may occur; this reaction is frequently dose-related.

Information For Patients:

Patients should maintain an adequate fluid intake to prevent crystalluria and stone formation.

Laboratory Tests:

Complete blood counts should be done frequently in patients receiving sulfonamides. If a significant reduction in the count of any formed blood element is noted, erythromycin ethylsuccinate and sulfisoxazole acetyl for oral suspension should be discontinued. Urinalysis with careful microscopic examination and renal function tests should be performed during therapy, particularly for those patients with impaired renal function. Blood levels should be measured in patients receiving a sulfonamide for serious infections. (See INDICATIONS AND USAGE.)

Drug Laboratory Test Interactions:

Erythromycin interferes with the fluorometric determination of urinary catecholamines.

Drug Interactions:

Erythromycin use in patients who are receiving high doses of theophylline may be associated with an increase in serum theophylline levels and potential theophylline toxicity. In case of theophylline toxicity and/or elevated serum theophylline levels, the dose of theophylline should be reduced while the patient is receiving concomitant erythromycin therapy.

Concomitant administration of erythromycin and digoxin has been reported to result in elevated digoxin serum levels.

There have been reports of increased anticoagulant effects when erythromycin and oral anticoagulants were used concomitantly. Increased anticoagulation effects due to this drug may be more pronounced in the elderly.

Concurrent use of erythromycin and ergotamine or dihydroergotamine has been associated in some patients with acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia.

Erythromycin has been reported to decrease the clearance of triazolam and midazolam and thus may increase the pharmacologic effect of these benzodiazepines.

The use of erythromycin in patients concurrently taking drugs metabolized by the cytochrome P450 system may be associated with elevations in serum levels of these other drugs. There have been reports of interactions of erythromycin with carbamazepine, cyclosporine, hexobarbital, phenytoin, allentanil, diisopyramide, lovastatin, and bromocriptine. Serum concentrations of drugs metabolized by the cytochrome P450 system should be monitored closely in patients concurrently receiving erythromycin.

Erythromycin significantly alters the metabolism of terfenadine when taken concomitantly. Rare cases of serious cardiovascular adverse events, including death, cardiac arrest, torsades de pointes, and other ventricular arrhythmias, have been observed. (See CONTRAINDICATIONS.)

It has been reported that sulfisoxazole may prolong the prothrombin time in patients who are receiving the anticoagulant warfarin. This interaction should be kept in mind when erythromycin ethylsuccinate and sulfisoxazole acetyl for oral suspension is given to patients already on anticoagulant therapy, and the coagulation time should be reassessed.

It has been proposed that sulfisoxazole competes with thiopental for plasma protein binding. In one study involving 48 patients, intravenous sulfisoxazole resulted in a decrease in the amount of thiopental required for anesthesia and in a shortening of the awakening time. It is not known whether chronic oral doses of sulfisoxazole have a similar effect. Until more is known about this interaction, physicians should be aware that patients receiving sulfisoxazole might require less thiopental for anesthesia.

Sulfonamides can displace methotrexate from plasma protein binding sites, thus increasing free methotrexate concentrations. Studies in man have shown sulfisoxazole infusions to decrease plasma protein-bound methotrexate by one fourth.

Sulfisoxazole can also potentiate the blood-sugar-lowering activity of sulfonylureas.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Carcinogenesis:

Erythromycin ethylsuccinate and sulfisoxazole acetyl for oral suspension has not undergone adequate trials relating to carcinogenicity: each component, however, has been evaluated separately. Long-term (21 month) oral studies conducted in rats with erythromycin ethylsuccinate did not provide evidence of tumorigenicity. Sulfisoxazole was not carcinogenic in either sex when administered to mice by gavage for 103 weeks at dosages up to approximately 18 times the recommended human dose or to rats at 4 times the human dose. Rats appear to be especially susceptible to the goitrogenic effects of sulfonamides, and long-term administration of sulfonamides has resulted in thyroid malignancies in this species.

Mutagenesis:

There are no studies available that adequately evaluate the mutagenic potential of erythromycin ethylsuccinate and sulfisoxazole acetyl for oral suspension or either of its components. However, sulfisoxazole was not observed to be mutagenic in E. coli Sd-4-73 when tested in the absence of a metabolic activating system. There was no apparent effect on male or female fertility in rats fed erythromycin (base) at levels up to 0.25% of diet.

Impairment of Fertility:

Erythromycin ethylsuccinate and sulfisoxazole acetyl for oral suspension has not undergone adequate trials relating to impairment of fertility. In a reproduction study in rats given 7 times the human dose per day of sulfisoxazole, no effects were observed regarding mating behavior, conception rate or fertility index (percent pregnant).

Pregnancy:

Teratogenic Effects:

Pregnancy Category C:

At dosages 7 times the human daily dose, sulfisoxazole was not teratogenic in either rats or rabbits. However, in two other teratogenicity studies, cleft palates developed in both rats and mice after administration of 5 to 9 times the human therapeutic dose of sulfisoxazole.

There is no evidence of teratogenicity or any other adverse effects on reproduction in female rats fed erythromycin base (up to 0.25% of diet) prior to and during mating, during gestation, and through weaning of two successive litters. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Erythromycin has been reported to cross the placental barrier in humans, but fetal plasma levels are generally low.

There are no adequate or well-controlled studies of erythromycin ethylsuccinate and sulfisoxazole acetyl for oral suspension in either laboratory animals or in pregnant women. It is not known whether erythromycin ethylsuccinate and sulfisoxazole acetyl for oral suspension can cause fetal harm when administered to a pregnant woman prior to term or can affect reproduction capacity. Erythromycin ethylsuccinate and sulfisoxazole acetyl for oral suspension should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects:

Kernicterus may occur in the newborn as a result of treatment of a pregnant woman at term with sulfonamides. (See CONTRAINDICATIONS:.)

Labor and Delivery:

The effects of Erythromycin and Sulfisoxazole on labor and delivery are unknown.

Nursing Mothers:

Both Erythromycin and Sulfisoxazole are excreted in human milk. Because of the potential for the development of kernicterus in neonates due to the displacement of bilirubin from plasma proteins by sulfisoxazole, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. (See CONTRAINDICATIONS:

Pediatric Use:

See INDICATIONS AND USAGE and DOSAGE AND ADMINISTRATION sections. Not for use in children under 2 months of age. (See CONTRAINDICATIONS.)

ADVERSE REACTIONS:

Erythromycin Ethylsuccinate:

The most frequent side effects of oral erythromycin preparations are gastrointestinal and are dose-related. They include nausea, vomiting, abdominal pain, diarrhea and anorexia. Symptoms of hepatic dysfunction and/or abnormal liver-function test results may occur (see WARNINGS section). Pseudomembranous colitis has been rarely reported in association with erythromycin therapy.

Allergic reactions ranging from urticaria and mild skin eruptions to anaphylaxis have occurred.

There have been isolated reports of reversible hearing loss occurring chiefly in patients with renal insufficiency and in patients receiving high doses of erythromycin.

Onset of pseudomembranous colitis symptoms may occur during of after antibiotic treatment. (See WARNINGS.)

Sulfisoxazole Acetyl:

Included in the listing that follows are adverse reactions that have been reported with other sulfonamide products: pharmacologic similarities require that each of the reactions be considered with erythromycin ethylsuccinate and sulfisoxazole acetyl for oral suspension administration.

Allergic/Dermatologic:

Anaphylaxis, erythema multiforme (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome), exfoliative dermatitis, angioedema, arteritis, vasculitis, allergic myocarditis, serum sickness, rash, urticaria, pruritus, photosensitivity, and conjunctival and scleral injection. In addition, periarteritis nodosa and systemic lupus erythematosus have been reported. (See WARNINGS.)

Cardiovascular:

Tachycardia, palpitations, syncope, and cyanosis.

Rarely, erythromycin has been associated with the production of ventricular arrhythmias, including ventricular tachycardia and torsade de pointes, in individuals with prolonged QT intervals.

Endocrine:

The sulfonamides bear certain chemical similarities to some goitrogens, diuretics (acetazolamide and the thiazides) and oral hypoglycemic agents. Cross-sensitivity may exist with these agents. Developments of goiter, diuresis, and hypoglycemia has occurred rarely in patients receiving sulfonamides.

Gastrointestinal:

Hepatitis, hepatocellular necrosis, jaundice, pseudomembranous colitis, nausea, emesis, anorexia, abdominal pain, diarrhea, gastrointestinal hemorrhage, melena, flatulence, glossitis, stomatitis, salivary gland enlargement, and pancreatitis. Onset of pseudomembranous colitis symptoms may occur during or after treatment with sulfisoxazole, a component of erythromycin ethylsuccinate and sulfisoxazole acetyl for oral suspension. (See WARNINGS.)

: The sulfisoxazole acetyl component of erythromycin ethylsuccinate and sulfisoxazole acetyl for oral suspension has been reported to cause increased elevation of liver-associated enzymes in patients with hepatitis.

Genitourinary:

Crystalluria, hematuria, BUN and creatinine elevations, nephritis, and toxic nephrosis with oliguria and anuria. Acute renal failure and urinary retention have also been reported.

: The frequency of renal complications, commonly associated with some sulfonamides, is lower in some patients receiving the more soluble sulfonamides such as sulfisoxazole.

Hematologic:

Leukopenia, agranulocytosis, aplastic anemia, thrombocytopenia, purpura, hemolytic anemia, anemia, eosinophilia, clotting disorders including hypopro-thrombinemia and hypofibrinogenemia, sulfhemoglobinemia, and methemoglobinemia.

Neurologic:

Headache, dizziness, peripheral neuritis, paresthesia, convulsions, tinnitus, vertigo, ataxia, and intracranial hypertension.

Psychiatric:

Psychosis, hallucinations, disorientation, depression, and anxiety.

Respiratory:

Cough, shortness of breath, and pulmonary infiltrates. (See WARNINGS)

Vascular:

Angioedema, arteritis, and vasculitis.

Miscellaneous:

Edema, (including periorbital), pyrexia, drowsiness, weakness, fatigue, lassitude, rigors, flushing, hearing loss, insomnia, and pneumonitis.

Overdosage:

No information is available on a specific result of overdose with erythromycin ethylsuccinate and sulfisoxazole acetyl for oral suspension. Overdosage of erythromycin should be handled with the prompt elimination of unabsorbed drug and all other appropriate measures. Erythromycin is not removed by peritoneal dialysis or hemodialysis.

The amount of a single dose of sulfisoxazole that is either associated with symptoms of overdosage or is likely to be life-threatening has not been reported. Signs and symptoms of overdosage reported with sulfonamides include anorexia, colic, nausea, vomiting, dizziness, headache, drowsiness and unconsciousness. Pyrexia, hematuria and crystalluria may be noted. Blood dyscrasias and jaundice are potential late manifestations of overdosage.

General principles of treatment include the immediate discontinuation of the drug, instituting gastric lavage or emesis, forcing oral fluids, and administering intravenous fluids if urine output is low and renal function is normal. The patient should be monitored with blood counts and appropriate blood chemistries, including electrolytes. If the patient becomes cyanotic, the possibility of methemoglobinemia should be considered and, if present, the condition should be treated appropriately with intravenous 1% methylene blue. If a significant blood dyscrasia or jaundice occurs, specific therapy should be instituted for these complications. Peritoneal dialysis is not effective, and hemodialysis is only moderately effective in removing sulfonamides.

The acute toxicity of sulfisoxazole in animals is as follows:

Species	LD50=S.E. (mg/kg)
mouse	5700 = 235
rats	± 10,000
rabbits	± 2000

DOSAGE AND ADMINISTRATION:

ERYTHROMYCIN ETHYLSUCCINATE AND SULFISOXAZOLE ACETYL FOR ORAL SUSPENSION SHOULD NOT BE ADMINISTERED TO INFANTS UNDER 2 MONTHS OF AGE BECAUSE OF CONTRAINDICATIONS OF SYSTEMIC SULFONAMIDES IN THIS AGE GROUP.

For Acute Otitis Media in Children:

The dose of erythromycin ethylsuccinate and sulfisoxazole acetyl for oral suspension can be calculated based on the erythromycin component (50 mg/kg/day) or the sulfisoxazole component (150 mg/kg/day to a maximum of 6 g/day). The total daily dose of erythromycin ethylsuccinate and sulfisoxazole acetyl for oral suspension should be administered in equally divided doses three or four times a day for 10 days. Erythromycin ethylsuccinate and sulfisoxazole acetyl for oral suspension may be administered without regard to meals.

The following approximate dosage schedules are recommended for using erythromycin ethylsuccinate and sulfisoxazole acetyl for oral suspension:

Children:

Two months of age or older

FOUR-TIMES-A-DAY SCHEDULE
Weight	Dose - every 6 hours
Less than 8 kg (<18 lbs)	Adjust dosage by body weight
8 kg (18 lbs)	1/2 teaspoonful (2.5 mL)
16 kg (35 lbs)	1 teaspoonful (5 mL)
24 kg (53 lbs)	1-1/2 teaspoonfuls (7.5 mL)
Over 32 kg (over 70 lbs)	2 teaspoonfuls (10 mL)
THREE-TIMES-A-DAY SCHEDULE
Weight	Dose - every 8 hours
Less than 6 kg (>13 lbs)	Adjust dosage by body weight
6 kg (13 lbs)	1/2 teaspoonful (2.5 mL)
12 kg (26 lbs)	1 teaspoonful (5 mL)
18 kg (40 lbs)	1-1/2 teaspoonfuls (7.5 mL)
24 kg (53 lbs)	2 teaspoonfuls (10 mL)
Over 30 kg (over 66 lbs)	2-1/2 teaspoonfuls (12.5 mL)

HOW SUPPLIED:

Erythromycin Ethylsuccinate and Sulfisoxazole Acetyl for Oral Suspension is available for teaspoon dosage in 100 mL (NDC 51285-445-22), 150 mL (NDC 51285-445-21) and 200 mL (NDC 51285-445-23) bottles, in the form of granules to be reconstituted with water. The suspension provides erythromycin ethylsuccinate equivalent to 200 mg erythromycin activity and sulfisoxazole acetyl equivalent to 600 mg sulfisoxazole per teaspoonful (5 mL).

Store at room temperature in dry form.

REFERENCES:

Biovert A, Barbeau G. Belanger PM: Pharmacokinetics of sulfisoxazole in young and elderly subjects. Gerontology 1984; 30: 125-131.

Oie S. Gambertoglio JG, Fleckenstein L: Comparison of the disposition of total and unbound sulfisoxazole after single and multiple dosing. J Pharmacokinet Biopharm 1982; 10: 157 - 172.

National Committee for Clinical Laboratory Standards: Performance Standards for Antimicrobial Disk Susceptibility Tests, ed 4. Approved Standard NCCLS Document M2-A4, Vol 10, No. 7. Villanova, Pa: NCCLS, 1990.

Manufactured by Duramed Pharmaceuticals, Inc.

Packaged by Pharmaceutics International, Inc.

Hunt Valley, Maryland 21031

for Duramed Pharmaceuticals, Inc.

Subsidiary of Barr Pharmaceuticals, Inc.

Pomona, NY 10970

Revised MARCH 2007

BR-0445

PRINCIPAL DISPLAY PANEL

100 mL Label Text

NDC 51285-445-22

E.S.P. (R)

Erythromycin Ethylsuccinate

and Sulfisoxazole Acetyl

for Oral Suspension, USP

200 mg erythromycin activity

and the equivalent of

600 mg sulfisoxazole

per 5 mL reconstituted

100 mL (when mixed) DURAMED(R) Rx only

ERYTHROMYCIN ETHYLSUCCINATE AND SULFISOXAZOLE ACETYL
erythromycin ethylsuccinate and sulfisoxazole acetyl granule, for suspension

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	NDC Product Code (Source)	51285-445
Route of Administration	ORAL	DEA Schedule

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
ERYTHROMYCIN ETHYLSUCCINATE (ERYTHROMYCIN)	ERYTHROMYCIN ETHYLSUCCINATE	200 mg in 5 mL
SULFISOXAZOLE ACETYL (SULFISOXAZOLE)	SULFISOXAZOLE ACETYL	600 mg in 5 mL

Inactive Ingredients
Ingredient Name	Strength
LACTOSE, ANHYDROUS
METHYLPARABEN
POLYSORBATE 80
POVIDONE
ANHYDROUS TRISODIUM CITRATE
SUCROSE

Product Characteristics
Color		Score
Shape		Size
Flavor	CHERRY	Imprint Code
Contains

Packaging
#	NDC	Package Description	Multilevel Packaging
1	51285-445-22	100 mL In 1 BOTTLE	None
2	51285-445-21	150 mL In 1 BOTTLE	None
3	51285-445-23	200 mL In 1 BOTTLE	None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA062759	05/20/1988

Labeler - Duramed Pharmaceuticals Inc. (017038951)

Revised: 11/2009Duramed Pharmaceuticals Inc.

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Otitis Media

Monday 8 October 2012

Elixophyllin

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Sunday 7 October 2012

Emcyt

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