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 CategoryExplanation
All TrimestersCAnimal 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

Other Medical Problems


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


  • Congestive heart failure or

  • Cor pulmonale (heart condition) or

  • Fever of 102 degrees F or higher for 24 hours or more or

  • Hypothyroidism (underactive thyroid) or

  • Infection, severe (e.g., sepsis) or

  • Kidney disease in infants younger than 3 months of age or

  • Liver disease (e.g., cirrhosis, hepatitis) or

  • Pulmonary edema (lung condition) or

  • Shock (serious condition with very little blood flow in the body)—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

  • Heart rhythm problems (e.g., arrhythmia) or

  • Seizures, or history of or

  • Stomach ulcer—Use with caution. May make these conditions worse.

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)



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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)



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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)



Compare Emcyt with other medications


  • Prostate Cancer

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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


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 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.


Other Medical Problems


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


  • Cushing's syndrome (adrenal gland disorder) or

  • Diabetes or

  • Hyperglycemia (high blood sugar) or

  • Intracranial hypertension (increased pressure in the head)—Use with caution. May make these conditions worse.

  • Infection of the skin at or near the place of application or

  • Large sores, broken skin, or severe skin injury at the place of application—The chance of side effects may be increased.

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


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


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


  • For 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

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:


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)



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 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

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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






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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 5HT1B/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 5HT1B/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 5HT1B/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 5HT1B/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 5HT1b/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 5HT1B and 5HT1D receptor subtypes. Zolmitriptan is a high affinity 5HT1B/1D receptor agonist with modest affinity for 5HT1A 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 5HT1B/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 Cmax 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. Cmax 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 Cmax 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 Cmax 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 Cmax 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 Cmax 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



UK



8. Marketing Authorisation Number(S)



PL 17901/0095



9. Date Of First Authorisation/Renewal Of The Authorisation



19th September 2002/ 18th June 2008



10. Date Of Revision Of The Text



4th October 2011




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