Kineldar

Kineldar may be available in the countries listed below.

Ingredient matches for Kineldar

Epalrestat

Epalrestat is reported as an ingredient of Kineldar in the following countries:

• Japan

International Drug Name Search

Arlidin

Arlidin may be available in the countries listed below.

Ingredient matches for Arlidin

Buphenine

Buphenine hydrochloride (a derivative of Buphenine) is reported as an ingredient of Arlidin in the following countries:

• India


• Mexico

International Drug Name Search

Oyslon

Oyslon may be available in the countries listed below.

Ingredient matches for Oyslon

Danazol

Danazol is reported as an ingredient of Oyslon in the following countries:

• Japan

International Drug Name Search

TheoCap

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 TheoCap

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 TheoCap

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

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 TheoCap. 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 TheoCap

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.

TheoCap 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: TheoCap 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 TheoCap resources

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

• TheoCap Concise Consumer Information (Cerner Multum)


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


• Theophylline Prescribing Information (FDA)


• Theophylline Professional Patient Advice (Wolters Kluwer)


• Elixophyllin Prescribing Information (FDA)


• Elixophyllin Elixir MedFacts Consumer Leaflet (Wolters Kluwer)


• Quibron-T MedFacts Consumer Leaflet (Wolters Kluwer)


• Quibron-T Prescribing Information (FDA)


• Theo-24 Prescribing Information (FDA)


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


• Theolair tablets Prescribing Information (FDA)


• Theophyllines Monograph (AHFS DI)


• Uniphyl Prescribing Information (FDA)

Compare TheoCap with other medications

• Apnea of Prematurity
• Asthma, acute
• Asthma, Maintenance

Metoject 50 mg / ml solution for injection

1. Name Of The Medicinal Product

Metoject 50 mg/ml solution for injection

2. Qualitative And Quantitative Composition

1 ml of solution contains 50 mg methotrexate (as methotrexate disodium).

1 pre-filled syringe of 0.15 ml contains 7.5 mg methotrexate.

1 pre-filled syringe of 0.20 ml contains 10 mg methotrexate. .

1 pre-filled syringe of 0.25 ml contains 12.5 mg methotrexate.

1 pre-filled syringe of 0.30 ml contains 15 mg methotrexate.

1 pre-filled syringe of 0.35 ml contains 17.5 mg methotrexate.

1 pre-filled syringe of 0.40 ml contains 20 mg methotrexate.

1 pre-filled syringe of 0.45 ml contains 22.5 mg methotrexate.

1 pre-filled syringe of 0.50 ml contains 25 mg methotrexate.

1 pre-filled syringe of 0.55 ml contains 27.5 mg methotrexate.

1 pre-filled syringe of 0.60 ml contains 30 mg methotrexate.

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Solution for injection, in pre-filled syringe.

Clear, yellow-brown solution.

4. Clinical Particulars

4.1 Therapeutic Indications

Metoject 50 mg/ml is indicated for the treatment of

− active rheumatoid arthritis in adult patients,

− polyarthritic forms of severe, active juvenile idiopathic arthritis, when the response to nonsteroidal anti-inflammatory drugs (NSAIDs) has been inadequate,

− severe recalcitrant disabling psoriasis, which is not adequately responsive to other forms of therapy such as phototherapy, PUVA, and retinoids, and severe psoriatic arthritis in adult patients.

4.2 Posology And Method Of Administration

Metoject 50 mg/ml should only be prescribed by physicians, who are familiar with the various characteristics of the medicinal product and its mode of action. Metoject 50 mg/ml is injected once weekly.

The patient is to be explicitly informed about the unusual fact of administration once weekly. It is advisable to determine a fixed, appropriate weekday as day of injection.

Methotrexate elimination is reduced in patients with a third distribution space (ascites, pleural effusions). Such patients require especially careful monitoring for toxicity, and require dose reduction or, in some cases, discontinuation of methotrexate administration (see section 5.2 and 4.4).

Dosage in adult patients with rheumatoid arthritis:

The recommended initial dose is 7.5 mg of methotrexate once weekly, administered either subcutaneously, intramuscularly or intravenously. Depending on the individual activity of the disease and tolerability by the patient, the initial dose may be increased gradually by 2.5 mg per week. A weekly dose of 25 mg should in general not be exceeded. However, doses exceeding 20 mg/week are associated with significant increase in toxicity, especially bone marrow suppression. Response to treatment can be expected after approximately 4 – 8 weeks. Upon achieving the therapeutically desired result, the dose should be reduced gradually to the lowest possible effective maintenance dose.

Dosage in children and adolescents below 16 years with polyarthritic forms of juvenile idiopathic arthritis

The recommended dose is 10-15 mg/m² body surface area (BSA)/once weekly. In therapy-refractory cases the weekly dosage may be increased up to 20mg/m² body surface area/once weekly. However, an increased monitoring frequency is indicated if the dose is increased.

Due to limited data availability about intravenous use in children and adolescents, parenteral administration is limited to subcutaneous and intramuscular injection.

Patients with JIA should always be referred to a rheumatology specialist in the treatment of children/adolescents.

Use in children < 3 years of age is not recommended as insufficient data on efficacy and safety are available for this population. (see section 4.4)

Dosage in patients with psoriasis vulgaris and psoriatic arthritis:

It is recommended that a test dose of 5 – 10 mg should be administered parenterally, one week prior to therapy to detect idiosyncratic adverse reactions. The recommended initial dose is 7.5 mg of methotrexate once weekly, administered either subcutaneously, intramuscularly or intravenously. The dose is to be increased gradually but should not, in general, exceed a weekly dose of 25 mg of methotrexate. Doses exceeding 20 mg per week can be associated with significant increase in toxicity, especially bone marrow suppression. Response to treatment can generally be expected after approximately 2 – 6 weeks. Upon achieving the therapeutically desired result, the dose should be reduced gradually to the lowest possible effective maintenance dose.

Patients with renal impairment:

Metoject 50 mg/ml should be used with caution in patients with impaired renal function. The dose should be adjusted as follows:

Creatinine clearance (ml/min)	Dose
> 50	100 %
20 – 50	50 %
< 20	Metoject 50 mg/ml must not be used

See section 4.3

The dose should be increased as necessary but should in general not exceed the maximum recommended weekly dose of 25 mg. In a few exceptional cases a higher dose might be clinically justified, but should not exceed a maximum weekly dose of 30 mg of methotrexate as toxicity will markedly increase.

Patients with hepatic impairment:

Methotrexate should be administered with great caution, if at all, to patients with significant current or previous liver disease, especially if due to alcohol. If bilirubin is > 5 mg/dl (85.5 µmol/l), methotrexate is contraindicated.

For a full list of contraindications, see section 4.3.

Use in elderly patients:

Dose reduction should be considered in elderly patients due to reduced liver and kidney function as well as lower folate reserves which occur with increased age.

Use in patient with a third distribution space (pleural effusions, ascitis):

As the half-life of Methotrexate can be prolonged to 4 times the normal length in patients who possess a third distribution space dose reduction or, in some cases, discontinuation of methotrexate administration may be required (see section 5.2 and 4.4).

Duration and method of administration:

The medicine is for single use only.

Metoject 50 mg/ml solution for injection can be given by intramuscular, intravenous or subcutaneous route (in children and adolescents only subcutaneous or intramuscular).

The overall duration of the treatment is decided by the physician.

Note:

If changing from oral to parenteral administration a reduction of the dose may be required due to the variable bioavailability of methotrexate after oral administration.

Folic acid supplementation may be considered according to current treatment guidelines.

4.3 Contraindications

Metoject 50 mg/ml is contraindicated in the case of

− hypersensitivity to methotrexate or to any of the excipients,

− liver insufficiency (see section 4.2),

− alcohol abuse,

− severe renal insufficiency (creatinine clearance less than 20 ml/min., see section 4.2 and section 4.4),

− pre-existing blood dyscrasias, such as bone marrow hypoplasia, leukopenia, thrombocytopenia, or significant anaemia,

− serious, acute or chronic infections such as tuberculosis, HIV or other immunodeficiency syndromes,

− ulcers of the oral cavity and known active gastrointestinal ulcer disease,

− pregnancy, breast-feeding (see section 4.6),

− concurrent vaccination with live vaccines.

4.4 Special Warnings And Precautions For Use

Patients must be clearly informed that the therapy has to be applicated once a week, not every day.

Patients undergoing therapy should be subject to appropriate supervision so that signs of possible toxic effects or adverse reactions may be detected and evaluated with minimal delay. Therefore methotrexate should be only administered by, or under the supervision of physicians whose knowledge and experience includes the use of antimetabolite therapy. Because of the possibility of severe or even fatal toxic reactions, the patient should be fully informed by the physician of the risks involved and the recommended safety measures.

Use in children < 3 years of age is not recommended as insufficient data on efficacy and safety are available for this population (see section 4.2).

Recommended examinations and safety measures

Before beginning or reinstituting methotrexate therapy after a rest period:

Complete blood count with differential blood count and platelets, liver enzymes, bilirubin, serum albumin, chest x-ray and renal function tests. If clinically indicated, exclude tuberculosis and hepatitis.

During therapy (at least once a month during the first six months and every three months thereafter):

An increased monitoring frequency should be considered also when the dose is increased.

1. Examination of the mouth and throat for mucosal changes

2. Complete blood count with differential blood count and platelets. Haemopoietic suppression caused by methotrexate may occur abruptly and with apparently safe dosages. Any profound drop in white-cell or platelet counts indicates immediate withdrawal of the medicinal product and appropriate supportive therapy. Patients should be advised to report all signs and symptoms suggestive of infection. Patients taking simultaneous administration of haematotoxic medicinal products (e.g. leflunomide) should be monitored closely with blood count and platelets.

3. Liver function tests: Particular attention should be given to the appearance of liver toxicity. Treatment should not be instituted or should be discontinued if any abnormality of liver function tests, or liver biopsy, is present or develops during therapy. Such abnormalities should return to normal within two weeks after which treatment may be recommenced at the discretion of the physician. There is no evidence to support use of a liver biopsy to monitor hepatic toxicity in rheumatological indications.

For psoriasis patients the need for a liver biopsy prior to and during therapy is controversial. Further research is needed to establish whether serial liver chemistry tests or propeptide of type III collagen can detect hepatotoxicity sufficiently. The evaluation should be performed case by case and differentiate between patients with no risk factors and patients with risk factors such as excessive prior alcohol consumption, persistent elevation of liver enzymes, history of liver disease, family history of inheritable liver disease, diabetes mellitus, obesity, and history of significant exposure to hepatotoxic drugs or chemicals and prolonged Methotrexate treatment or cumulative doses of 1.5 g or more.

Check of liver-related enzymes in serum: Temporary increases in transaminases to twice or three times of the upper limit of normal have been reported by patients at a frequency of 13 – 20 %. In the case of a constant increase in liver-related enzymes, a reduction of the dose or discontinuation of therapy should be taken into consideration.

Due to its potentially toxic effect on the liver, additional hepatotoxic medicinal products should not be taken during treatment with methotrexate unless clearly necessary and the consumption of alcohol should be avoided or greatly reduced (see section 4.5). Closer monitoring of liver enzymes should be exercised in patients taking other hepatotoxic medicinal products concomitantly (e.g. leflunomide). The same should be taken into account with the simultaneous administration of haematotoxic medicinal products (e.g. leflunomide).

4. Renal function should be monitored by renal function tests and urinanalysis (see sections 4.2 and 4.3).

As methotrexate is eliminated mainly by renal route, increased serum concentrations are to be expected in the case of renal insufficiency, which may result in severe undesirable effects.

Where renal function may be compromised (e.g. in the elderly), monitoring should take place more frequently. This applies in particular, when medicinal products are administered concomitantly, which affect the elimination of methotrexate, cause kidney damage (e.g. non-steroidal anti-inflammatory medicinal products) or which can potentially lead to impairment of blood formation. Dehydration may also intensify the toxicity of methotrexate.

5. Assessment of respiratory system: Alertness for symptoms of lung function impairment and, if necessary lung function test. Pulmonary affection requires a quick diagnosis and discontinuation of methotrexate. Pulmonary symptoms (especially a dry, non-productive cough) or a non-specific pneumonitis occurring during methotrexate therapy may be indicative of a potentially dangerous lesion and require interruption of treatment and careful investigation. Acute or chronic interstitial pneumonitis, often associated with blood eosinophilia, may occur and deaths have been reported. Although clinically variable, the typical patient with methotrexate-induced lung disease presents with fever, cough, dyspnoea, hypoxemia, and an infiltrate on chest X

6. Methotrexate may, due to its effect on the immune system, impair the response to vaccination results and affect the result of immunological tests. Particular caution is also needed in the presence of inactive, chronic infections (e.g. herpes zoster, tuberculosis, hepatitis B or C) for reasons of eventual activation. Vaccination using live vaccines must not be carried out under methotrexate therapy.

Malignant lymphomas may occur in patients receiving low dose methotrexate, in which case therapy must be discontinued. Failure of the lymphoma to show signs of spontaneous regression requires the initiation of cytotoxic therapy.

Concomitant administration of folate antagonists such as trimethoprim/sulphamethoxazole has been reported to cause an acute megaloblastic pancytopenia in rare instances.

Radiation induced dermatitis and sun-burn can reappear under methotrexate therapy (recall-reaction). Psoriatic lesions can exacerbate during UV-irradiation and simultaneous administration of methotrexate.

Methotrexate elimination is reduced in patients with a third distribution space (ascites, pleural effusions). Such patients require especially careful monitoring for toxicity, and require dose reduction or, in some cases, discontinuation of methotrexate administration. Pleural effusions and ascites should be drained prior to initiation of methotrexate treatment (see section 5.2).

Diarrhoea and ulcerative stomatitis can be toxic effects and require interruption of therapy, otherwise haemorrhagic enteritis and death from intestinal perforation may occur.

Vitamin preparations or other products containing folic acid, folinic acid or their derivatives may decrease the effectiveness of methotrexate.

For the treatment of psoriasis, methotrexate should be restricted to severe recalcitrant, disabling psoriasis which is not adequately responsive to other forms to other forms of therapy, but only when the diagnosis has been established by biopsy and/or after dermatological consultation.

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially "sodium

The absence of pregnancy should be confirmed before Metoject 50 mg/ml is administered. Methotrexate causes embryotoxicity, abortion and foetal defects in humans. Methotrexate affects spermatogenesis and oogenesis during the period of its administration which may result in decreased fertility. These effects appear to be reversible on discontinuing therapy. Effective contraception in men and women should be performed during treatment and for at least six months thereafter. The possible risks of effects on reproduction should be discussed with patients of childbearing potential and their partners should be advised appropriately (see section 4.6).

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Alcohol, hepatotoxic medicinal products, haematotoxic medicinal products

The probability of methotrexate exhibiting a hepatotoxic effect is increased by regular alcohol consumption and when other hepatotoxic medicinal products are taken at the same time (see section 4.4). Patients taking other hepatotoxic medicinal products concomitantly (e.g. leflunomide) should be monitored with special care. The same should be taken into account with the simultaneous administration of haematotoxic medicinal products (e.g. leflunomide, azathioprine, retinoids, sulfasalazine). The incidence of pancytopenia and hepatotoxicity can be increased when leflunomide is combined with methotrexate.

Combined treatment with methotrexate and retinoids like acitretin or etretinate increases the risk of hepatotoxicity.

Oral antibiotics

Oral antibiotics like tetracyclines, chloramphenicol, and non-absorbable broad-spectrum antibiotics can interfere with the enterohepatic circulation, by inhibition of the intestinal flora or suppression of the bacterial metabolism.

Antibiotics

Antibiotics, like penicillines, glycopeptides, sulfonamides, ciprofloxacin and cefalotin can, in individual cases, reduce the renal clearance of methotrexate, so that increased serum concentrations of methotrexate with simultaneous haematological and gastro-intestinal toxicity may occur.

Medicinal products with high plasma protein binding

Methotrexate is plasma protein bound and may be displaced by other protein bound drugs such as salicylates, hypoglycaemics, diuretics, sulphonamides, diphenylhydantoins, tetracyclines, chloramphenicol and p-aminobenzoic acid, and the acidic anti-inflammatory agents, which can lead to increased toxicity when used concurrently.

Probenecid, weak organic acids, pyrazoles and non-steroidal anti-inflammatory agents

Probenecid, weak organic acids such as loop diuretics, and pyrazoles (phenylbutazone) can reduce the elimination of methotrexate and higher serum concentrations may be assumed inducing higher haematological toxicity. There is also a possibility of increased toxicity when low dose methotrexate and non steroidal anti-inflammatory medicinal products or salicylates are combined.

Medicinal products with adverse reactions on the bone marrow

In the case of medication with medicinal products, which may have adverse reactions on the bone marrow (e.g. sulphonamides, trimethoprim-sulphamethoxazole, chloramphenicol, pyrimethamine); attention should be paid to the possibility of pronounced impairment of blood formation.

Medicinal products which cause folate deficiency

The concomitant administration of products which cause folate deficiency (e.g. sulphonamides, trimethoprim-sulphamethoxazole) can lead to increased methotrexate toxicity. Particular care is therefore advisable in the presence of existing folic acid deficiency.

Products containing folic acid or folinic acid

Vitamin preparations or other products containing folic acid, folinic acid or their derivatives may decrease the effectiveness of methotrexate.

Other antirheumatic medicinal products

An increase in the toxic effects of methotrexate is, in general, not to be expected when Metoject 50 mg/ml is administered simultaneously with other antirheumatic medicinal products (e.g. gold compounds, penicillamine, hydroxychloroquine, sulphasalazine, azathioprine, ciclosporin).

Sulphasalazine

Although the combination of methotrexate and sulphasalazine can cause an increase in efficacy of methotrexate and as a result more undesirable effects due to the inhibition of folic acid synthesis through sulphasalazine, such undesirable effects have only been observed in rare individual cases in the course of several studies.

Mercaptopurine

Methotrexate increases the plasma levels of mercaptopurine. The combination of methotrexate and mercaptopurine may therefore require dose adjustment.

Proton-pump inhibitors

A concomitant administration of proton-pump inhibitors like omeprazole or pantoprazole can lead to interactions: Concomitant administration of methotrexate and omeprazole has led to delayed renal elimination of methotrexate. In combination with pantoprazole inhibited renal elimination of the metabolite 7-hydroxymethotrexate with myalgia and shivering was reported in one case.

Theophylline

Methotrexate may decrease the clearance of theophylline; theophylline levels should be monitored when used concurrently with methotrexate.

Caffeine- or theophylline-containing beverages

An excessive consumption of caffeine- or theophylline-containing beverages (coffee, caffeine-containing soft drinks, black tea) should be avoided during methotrexate therapy.

4.6 Pregnancy And Lactation

Metoject 50 mg/ml is contraindicated during pregnancy (see section 4.3). In animal studies, methotrexate has shown reproductive toxicity (see section 5.3). Methotrexate has been shown to be teratogenic to humans; it has been reported to cause foetal death and/or congenital abnormalities. Exposure of a limited number of pregnant women (42) resulted in an increased incidence (1:14) of malformations (cranial, cardiovascular and extremital). If methotrexate is discontinued prior to conception, normal pregnancies have been reported. Women must not get pregnant during methotrexate therapy. In case of women getting pregnant during therapy medical counselling about the risk of adverse reactions for the child associated with methotrexate therapy should be sought. Therefore, patients of a sexually mature age (women and men) must use effective contraception during treatment with Metoject 50 mg/ml and at least 6 months thereafter (see section 4.4).

In women of child-bearing age, any existing pregnancy must be excluded with certainty by taking appropriate measures, e.g. pregnancy test, prior to initiating therapy.

As methotrexate can be genotoxic, all women who wish to become pregnant are advised to consult a genetic counselling centre, if possible, already prior to therapy, and men should seek advice about the possibility of sperm preservation before starting therapy.

Lactation: Methotrexate is excreted in breast milk in such concentrations that there is a risk for the infant, and accordingly, breast-feeding should be discontinued prior to and throughout administration.

4.7 Effects On Ability To Drive And Use Machines

Central nervous symptoms such as tiredness and dizziness can occur during treatment, Metoject 50 mg/ml has minor or moderate influence on the ability to drive and use machines.

4.8 Undesirable Effects

The most relevant undesirable effects are suppression of the haematopoietic system and gastrointestinal disorders.

The following headings are used to organise the undesirable effects in order of frequency:

Very common (

Gastrointestinal disorders

Very common: Stomatitis, dyspepsia, nausea, loss of appetite.

Common: Oral ulcers, diarrhoea.

Uncommon: Pharyngitis, enteritis, vomiting.

Rare: Gastrointestinal ulcers.

Very rare: Haematemesis, haematorrhea, toxic megacolon.

Skin and subcutaneous tissue disorders

Common: Exanthema, erythema, pruritus.

Uncommon: Photosensitisation, loss of hair, increase in rheumatic nodules, herpes zoster, vasculitis, herpetiform eruptions of the skin, urticaria.

Rare: Increased pigmentation, acne, ecchymosis.

Very rare: Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), increased pigmentary changes of the nails, acute paronychia, furunculosis, telangiectasia.

General disorders and administration site conditions

Rare: Allergic reactions, anaphylactic shock, allergic vasculitis, fever, conjunctivitis, infection, sepsis, wound-healing impairment, hypogammaglobulinaemia.

Very rare: Local damage (formation of sterile abscess, lipodystrophy) of injection site following intramuscular or subcutaneous administration.

Metabolism and nutrition disorders

Uncommon: Precipitation of diabetes mellitus.

Nervous system disorders

Common: Headache, tiredness, drowsiness.

Uncommon: Dizziness, confusion, depression.

Very rare: Impaired vision, pain, muscular asthenia or paraesthesia in the extremities, changes in sense of taste (metallic taste), convulsions, meningism, paralysis.

Eye disorders

Rare: Visual disturbances.

Very rare: Retinopathy.

Hepatobiliary disorders (see section 4.4)

Very common: Elevated transaminases.

Uncommon: Cirrhosis, fibrosis and fatty degeneration of the liver, decrease in serum albumin.

Rare: Acute hepatitis.

Very rare: Hepatic failure.

Cardiac disorders

Rare: Pericarditis, pericardial effusion, pericardial tamponade.

Vascular disorders

Rare: Hypotension, thromboembolic events.

Respiratory, thoracic and mediastinal disorders

Common: Pneumonia, interstitial alveolitis/pneumonitis often associated with eosinophilia. Symptoms indicating potentially severe lung injury (interstitial pneumonitis) are: dry, not productive cough, short of breath and fever.

Rare: Pulmonary fibrosis, Pneumocystis carinii pneumonia, shortness of breath and bronchial asthma, pleural effusion.

Blood and lymphatic system disorders

Common: Leukopenia, anaemia, thrombopenia.

Uncommon: Pancytopenia.

Very rare: Agranulocytosis, severe courses of bone marrow depression.

Renal and urinary disorders

Uncommon: Inflammation and ulceration of the urinary bladder, renal impairment, disturbed micturition.

Rare: Renal failure, oliguria, anuria, electrolyte disturbances.

Reproductive system and breast disorders

Uncommon: Inflammation and ulceration of the vagina.

Very rare: Loss of libido, impotence, gynaecomastia, oligospermia, impaired menstruation, vaginal discharge.

Musculoskeletal and connective tissue disorders

Uncommon: Arthralgia, myalgia, osteoporosis.

Neoplasms benign, malignant and unspecified (including cysts and polyps)

Very rare: There have been reports of individual cases of lymphoma which subsided in a number of cases once treatment with methotrexate had been discontinued. In a recent study, it could not be established that methotrexate therapy increases the incidence of lymphomas.

The appearance and degree of severity of undesirable effects depends on the dosage level and the frequency of administration. However, as severe undesirable effects can occur even at lower doses, it is indispensable that patients are monitored regularly by the doctor at short intervals.

When methotrexate is given by the intramuscular route, local undesirable effects (burning sensation) or damage (formation of sterile abscess, destruction of fatty tissue) at the site of injection can occur commonly. Subcutaneous application of methotrexate is locally well tolerated. Only mild local skin reactions were observed, decreasing during therapy.

4.9 Overdose

a) Symptoms of overdosage

Toxicity of methotrexate mainly affects the haematopoietic system.

b) Treatment measures in the case of overdosage

Calcium folinate is the specific antidote for neutralising the toxic undesirable effects of methotrexate.

In cases of accidental overdose, a dose of calcium folinate equal to or higher than the offending dose of methotrexate should be administered intravenously or intramuscularly within one hour and dosing continued until the serum levels of methotrexate are below 10 mol/l.

In cases of massive overdose, hydration and urinary alkalisation may be necessary to prevent precipitation of methotrexate and/or its metabolites in the renal tubules. Neither haemodialysis nor peritoneal dialysis has been shown to improve methotrexate elimination. Effective clearance of methotrexate has been reported with acute, intermittent haemodialysis using a high flux dialyser.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Folic acid analogues

ATC code: L01BA01

Antirheumatic medicinal product for the treatment of chronic, inflammatory rheumatic diseases and polyarthritic forms of juvenile idiopathic arthritis.

Methotrexate is a folic acid antagonist which belongs to the class of cytotoxic agents known as antimetabolites. It acts by the competitive inhibition of the enzyme dihydrofolate reductase and thus inhibits DNA synthesis. It has not yet been clarified, as to whether the efficacy of methotrexate, in the management of psoriasis, psoriasis arthritis and chronic polyarthritis, is due to an anti-inflammatory or immunosuppressive effect and to which extent a methotrexate-induced increase in extracellular adenosine concentration at inflamed sites contributes to these effects.

5.2 Pharmacokinetic Properties

Following oral administration, methotrexate is absorbed from the gastrointestinal tract. In case of low-dosed administration (dosages between 7.5 mg/m² and 80 mg/m² body surface area), the mean bioavailability is approx. 70 %, but considerable interindividual and intraindividual deviations are possible (25 – 100 %). Maximum serum concentrations are achieved after 1 – 2 hours.

Bioavailability of subcutaneous, intravenous and intramuscular injection is comparable and nearly 100 %.

Approximately 50 % of methotrexate is bound to serum proteins. Upon being distributed into body tissues, high concentrations in the form of polyglutamates are found in the liver, kidneys and spleen in particular, which can be retained for weeks or months. When administered in small doses, methotrexate passes into the liquor in minimal amounts. The terminal half-life is on average 6 – 7 hours and demonstrates considerable variation (3 – 17 hours). The half-life can be prolonged to 4 times the normal length in patients who possess a third distribution space (pleural effusion, ascites).

Approx. 10 % of the administered methotrexate dose is metabolised intrahepatically. The principle metabolite is 7

Excretion takes places, mainly in unchanged form, primarily renal via glomerular filtration and active secretion in the proximal tubulus.

Approx. 5 – 20 % methotrexate and 1 – 5 % 7

In the case of renal insufficiency, elimination is delayed significantly. Impaired elimination with regard to hepatic insufficiency is not known.

5.3 Preclinical Safety Data

Animal studies show that methotrexate impairs fertility, is embryo- and foetotoxic and teratogenic. Methotrexate is mutagenic in vivo and in vitro. As conventional carcinogenicity studies have not been performed and data from chronic toxicity studies in rodents are inconsistent, methotrexate is considered not classifiable as to its carcinogenicity to humans.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Sodium chloride

Sodium hydroxide for pH adjustment

Water for injections

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3 Shelf Life

2 years.

6.4 Special Precautions For Storage

Store below 25 °C. Keep the pre-filled syringes in the outer carton in order to protect from light.

6.5 Nature And Contents Of Container

Nature of container:

Pre-filled syringes of colourless glass (type I) of 1 ml capacity with attached injection needle. Plunger stoppers of chlorobutyl rubber (type I) and polystyrene rods inserted on the stopper to form the syringe plunger

or

Pre-filled syringes of colourless glass (type I) of 1 ml capacity with enclosed injection needle.Plunger stoppers of chlorobutyl rubber (type I) and polystyrene rods inserted on the stopper to form the syringe plunger.

Pack sizes:

Pre-filled syringes containing 0.15 ml, 0.20 ml, 0.25 ml, 0.30 ml, 0.35 ml, 0.40 ml, 0.45 ml, 0.50 ml, 0.55 ml or 0.60 ml solution are available in packs of 1, 4, 6, 12 and 24 syringes with attached s.c. injection needle and alcohol pads.

and

Pre-filled syringes containing 0.15 ml, 0.20 ml, 0.25 ml, 0.30 ml, 0.35 ml, 0.40 ml, 0.45 ml, 0.50 ml,0.55 ml or 0.60 ml solution are available in packs of 1, 4, 6, 12 and 24 syringes with enclosed s.c. injection needle and alcohol pads.

All pack sizes are available with graduation marks.

Not all pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

The manner of handling and disposal must be consistent with that of other cytotoxic preparations in accordance with local requirements. Pregnant health care personnel should not handle and/or administer Metoject 50 mg/ml.

Methotrexate should not come into contact with the skin or mucosa. In the event of contamination, the affected area must be rinsed immediately with ample amount of water.

For single use only.

Any unused product or waste should be disposed of in accordance with local requirements.

7. Marketing Authorisation Holder

medac

Gesellschaft für klinische Spezialpräparate mbH

Fehlandtstraße 3

20354 Hamburg

Germany

8. Marketing Authorisation Number(S)

PL 11587/0046

9. Date Of First Authorisation/Renewal Of The Authorisation

21/11/2008

10. Date Of Revision Of The Text

27/10/2010

Earex Plus Ear Drops

1. Name Of The Medicinal Product

Earex Plus Ear Drops.

2. Qualitative And Quantitative Composition

Choline Salicylate Solution BP 43.22% w/v; and Glycerol BP 12.62% w/v.

3. Pharmaceutical Form

Solution for topical administration to the ear.

4. Clinical Particulars

4.1 Therapeutic Indications

For the symptomatic relief of ear pain in acute and chronic otitis media and externa. Patients with ear pain should always seek medical advice. Softening of ear wax as an aid to ear wax removal.

4.2 Posology And Method Of Administration

Auricular Use. Adults, the elderly and children: For pain relief: With the head tilted to one side, the external ear canal is filled completely with Earex Plus Ear Drops using the dropper provided. The ear should be plugged with cotton wool soaked with the ear drops. A wick may be inserted, if preferred, using the ear drops to keep it moist. Earex Plus Ear Drops should be instilled every three to four hours. For the softening of ear wax: Apply as described above, twice daily, for four days.

4.3 Contraindications

Not to be used in children under one year of age without medical advice being sought. Salicylate sensitivity. Perforated ear drum. Hypersensitivity to any of the ingredients.

4.4 Special Warnings And Precautions For Use

None stated.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

None stated.

4.6 Pregnancy And Lactation

There is no known hazard with the use of this product during pregnancy and lactation.

4.7 Effects On Ability To Drive And Use Machines

None stated.

4.8 Undesirable Effects

None stated.

4.9 Overdose

Each bottle of Earex Plus Ear Drops contains 1.6g of choline salicylate, equivalent to 1.2g of aspirin. Accidental or deliberate ingestion of the contents of a bottle of Earex Plus Ear Drops is therefore only of concern in small infants. In such cases, signs of intoxication may include dizziness, tinnitus, sweating, vomiting, confusion and hyperventilation. Gross overdosage may lead to central nervous system depression. Management should include, as appropriate, induced vomiting, correction of fluid and electrolyte balance and measurement of plasma salicylate levels. At concentrations in excess of 300mg/litre measures such as forced alkaline diuresis and haemodialysis to enhance clearance may be appropriate.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Choline salicylate ATC code: N02BA03.

Choline salicylate has actions similar to those of aspirin, that is analgesic, anti-inflammatory and antipyretic actions considered to be due to inhibition of the biosynthesis of prostaglandins. Glycerol softens ear wax due to its water-retaining and emollient properties.

5.2 Pharmacokinetic Properties

Not applicable as Earex Plus Ear Drops are applied topically.

5.3 Preclinical Safety Data

None stated.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Ethylene Oxide Polyoxypropylene Glycol; Chlorbutol (Hemihydrate); Hydrochloric Acid; Propylene Glycol.

6.2 Incompatibilities

None stated.

6.3 Shelf Life

Three years unopened.

6.4 Special Precautions For Storage

Do not store above 25^oC.

6.5 Nature And Contents Of Container

Cartoned amber glass bottle with screw cap and integral dropper containing 10ml of product.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

SSL International PLC. Venus, 1 Old Park Lane, Trafford Park, Manchester, M41 7HA.

8. Marketing Authorisation Number(S)

PL 17905/0018

9. Date Of First Authorisation/Renewal Of The Authorisation

21/08/2006

10. Date Of Revision Of The Text

21/08/2006

L-Thyroxin beta

L-Thyroxin beta may be available in the countries listed below.

Ingredient matches for L-Thyroxin beta

Levothyroxine

Levothyroxine sodium salt (a derivative of Levothyroxine) is reported as an ingredient of L-Thyroxin beta in the following countries:

• Germany

International Drug Name Search

Dicycloverine 10mg / 5ml syrup

1. Name Of The Medicinal Product

Merbentyl Syrup

Dicycloverine Hydrocholoride 10mg/5ml Syrup

2. Qualitative And Quantitative Composition

Dicycloverine Hydrochloride 10mg

3. Pharmaceutical Form

Syrup

4. Clinical Particulars

4.1 Therapeutic Indications

Dicycloverine hydrochloride is a smooth muscle antispasmodic primarily indicated for treatment of functional conditions involving smooth muscle spasm of the gastrointestinal tract. The commonest of these are irritable colon (mucous colitis, spastic colon).

4.2 Posology And Method Of Administration

Adults

One to two 5ml spoonfuls (10 - 20mg) three times daily before or after meals.

Children (2-12 years):

One 5ml spoonful (10mg) three times daily.

Children (6 months - 2 years)

5 - 10mg three or four times daily, 15 minutes before feeds. Do not exceed a daily dose of 40mg. If it is necessary to dilute Dicycloverine hydrochloride Syrup this may be done using Syrup or if diluted immediately prior to use with water.

4.3 Contraindications

Known idiosyncrasy to dicycloverine hydrochloride. Infants under 6 months of age.

Patients with rare hereditary problems of fructose intolerance, glucose galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

4.4 Special Warnings And Precautions For Use

Products containing dicycloverine hydrochloride should be used with caution in any patient with or suspected of having glaucoma or prostatic hypertrophy. Use with care in patients with hiatus hernia associated with reflux oesophagitis because anticholinergic drugs may aggravate the condition. There are reports of infants, 3 months of age and under, administered dicycloverine hydrochloride syrup who have evidenced respiratory symptoms (breathing difficulty, shortness of breath, breathlessness, respiratory collapse, apnoea) as well as seizures, syncope, asphyxia, pulse rate fluctuations, muscular hypotonia and coma. The above symptoms have occurred within minutes of ingestion and lasted 20-30 minutes. The symptoms were reported in association with dicycloverine hydrochloride syrup therapy but the cause and effect relationship has neither been disproved or proved. The timing and nature of the reactions suggest that they were a consequence of local irritation and/or aspiration, rather than to a direct pharmacological effect. Although no causal relationship between these effects, observed in infants and dicycloverine administration has been established, dicycloverine hydrochloride is contra-indicated in infants under 6 months of age.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

None stated.

4.6 Pregnancy And Lactation

Epidemiological studies in pregnant women with products containing dicycloverine hydrochloride (at doses up to 40mg/day) have not shown that dicycloverine hydrochloride increases the risk of foetal abnormalities if administered during the first trimester of pregnancy. Reproduction studies have been performed in rats and rabbits at doses of up to 100 times the maximum recommended dose (based on 60mg per day for an adult person) and have revealed no evidence of impaired fertility or harm to the foetus due to dicycloverine. Since the risk of teratogenicity cannot be excluded with absolute certainty for any product, the drug should be used during pregnancy only if clearly needed.

It is not known whether dicycloverine is secreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when dicycloverine is administered to a nursing mother.

4.7 Effects On Ability To Drive And Use Machines

None stated.

4.8 Undesirable Effects

Side-effects seldom occur with Dicycloverine hydrochloride. However, in susceptible individuals, dry mouth, thirst and dizziness may occur. On rare occasions, fatigue, sedation, blurred vision, rash, constipation, anorexia, nausea and vomiting, headache and dysuria have also been reported.

4.9 Overdose

Symptoms of Dicycloverine hydrochloride overdosage are headache, dizziness, nausea, dry mouth, difficulty in swallowing, dilated pupils and hot dry skin. Treatment may include emetics, gastric lavage and symptomatic therapy if indicated.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Dicycloverine hydrochloride relieves smooth muscle spasm of the gastrointestinal tract.

Animal studies indicate that this action is achieved via a dual mechanism;

(1) a specific anticholinergic effect (antimuscarinic at the ACh-receptor sites) and

(2) a direct effect upon smooth muscle (musculotropic).

5.2 Pharmacokinetic Properties

After a single oral 20mg dose of dicycloverine hydrochloride in volunteers, peak plasma concentration reached a mean value of 58ng/ml in 1 to 1.5 hours. ¹⁴C labelled studies demonstrated comparable bioavailability from oral and intravenous administration. The principal route of elimination is via the urine.

5.3 Preclinical Safety Data

None stated.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Invert Syrup Medium

Citric Acid Monohydrate

Sodium Benzoate

Raspberry Flavour

Wild Cherry Bark Flavour

Blackcurrant Essence

Vanilla Essence

Purified water

6.2 Incompatibilities

None stated.

6.3 Shelf Life

3 years.

6.4 Special Precautions For Storage

Do not store above 25°C. Should be stored and dispensed in amber glass bottles.

6.5 Nature And Contents Of Container

Type III, EP amber glass bottles sealed with a polyethylene screw cap equiped with a polyethylene seal and pilferproof closure.

Pack sizes:	1 bottle containing 500ml syrup.
	1 bottle containing 120ml syrup.

6.6 Special Precautions For Disposal And Other Handling

None stated.

7. Marketing Authorisation Holder

Zentiva

One Onslow Street

Guildford

Surrey

GU1 4YS

United Kingdom

8. Marketing Authorisation Number(S)

PL 17780/0564

9. Date Of First Authorisation/Renewal Of The Authorisation

16-03-2011

10. Date Of Revision Of The Text

19-04-2011

LEGAL CATEGORY

POM

BLyS-specific inhibitors

Drug List:

Vitamina B12

Vitamina B12 may be available in the countries listed below.

Ingredient matches for Vitamina B12

Cyanocobalamin

Cyanocobalamin is reported as an ingredient of Vitamina B12 in the following countries:

• Peru


• Venezuela

Hydroxocobalamin

Hydroxocobalamin is reported as an ingredient of Vitamina B12 in the following countries:

• Venezuela

International Drug Name Search

Novolin R PenFill

Generic Name: insulin regular (IN soo lin REG yoo lar)

Brand Names: HumuLIN R, NovoLIN R, NovoLIN R Innolet, NovoLIN R PenFill, ReliOn/NovoLIN R

What is Novolin R PenFill (insulin regular)?

Insulin is a hormone that is produced in the body. It works by lowering levels of glucose (sugar) in the blood. Insulin regular is a short-acting form of insulin.

Insulin regular is used to treat diabetes.

Insulin regular may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about Novolin R PenFill (insulin regular)?

Take care not to let your blood sugar get too low. Low blood sugar (hypoglycemia) can occur if you skip a meal, exercise too long, drink alcohol, or are under stress. Symptoms include headache, hunger, weakness, sweating, tremors, irritability, or trouble concentrating. Carry hard candy or glucose tablets with you in case you have low blood sugar. Other sugar sources include orange juice and milk. Be sure your family and close friends know how to help you in an emergency.

Also watch for signs of blood sugar that is too high (hyperglycemia). These symptoms include increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, and weight loss. Your blood sugar will need to be checked often, and you may need to adjust your insulin dose.

Never share an injection pen or cartridge with another person. Sharing injection pens or cartridges can allow disease such as hepatitis or HIV to pass from one person to another.

Insulin is only part of a complete program of treatment that may also include diet, exercise, weight control, foot care, eye care, dental care, and testing your blood sugar. Follow your diet, medication, and exercise routines very closely. Changing any of these factors can affect your blood sugar levels.

Do not change the brand of insulin or syringe you are using without first talking to your doctor or pharmacist. Some brands of insulin regular and syringes are interchangeable, while others are not. Your doctor and/or pharmacist know which brands can be substituted for one another.

What should I discuss with my healthcare provider before using Novolin R PenFill (insulin regular)?

Do not use this medication if you are allergic to insulin, or if you are having an episode of hypoglycemia (low blood sugar).

To make sure you can safely use insulin, tell your doctor if you have liver or kidney disease.

Tell your doctor about all other medications you use, including any oral (by mouth) diabetes medications.

Insulin regular is only part of a complete program of treatment that may also include diet, exercise, weight control, foot care, eye care, dental care, and testing your blood sugar. Follow your diet, medication, and exercise routines very closely. Changing any of these factors can affect your blood sugar levels.

FDA pregnancy category B. Insulin is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether insulin regular passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I use Novolin R PenFill (insulin regular)?

Use exactly as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Your blood sugar will need to be checked often, and you may need other blood tests at your doctor's office. Visit your doctor regularly.

Insulin regular is injected under the skin. You may be shown how to use injections at home. Do not self inject this medicine if you do not fully understand how to give the injection and properly dispose of used needles and syringes.

Choose a different place in your injection skin area each time you use this medication. Do not inject into the same place two times in a row.

Insulin regular should look as clear as water. Do not use the medication if has changed colors, looks cloudy, or has particles in it. Call your doctor for a new prescription.

Use a disposable needle only once. Throw away used needles in a puncture-proof container (ask your pharmacist where you can get one and how to dispose of it). Keep this container out of the reach of children and pets.

Some types of insulin needles can be used more than once. But reusing needles increases your risk of infection. Used needles must be properly cleaned and inspected for bending or breakage. Ask your doctor or pharmacist whether you can reuse your insulin needles.

Never share an injection pen or cartridge with another person. Sharing injection pens or cartridges can allow disease such as hepatitis or HIV to pass from one person to another. Know the signs of low blood sugar (hypoglycemia) and how to recognize them: headache, hunger, weakness, sweating, tremors, irritability, or trouble concentrating.

Always keep a source of sugar available in case you have symptoms of low blood sugar. Sugar sources include orange juice, glucose gel, candy, or milk. If you have severe hypoglycemia and cannot eat or drink, use an injection of glucagon. Your doctor can give you a prescription for a glucagon emergency injection kit and tell you how to give the injection.

Also watch for signs of blood sugar that is too high (hyperglycemia). These symptoms include increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, and weight loss.

Check your blood sugar carefully during a time of stress or illness, if you travel, exercise more than usual, drink alcohol, or skip meals. These things can affect your glucose levels and your dose needs may also change.

Your doctor may want you to stop taking insulin for a short time if you become ill, have a fever or infection, or if you have surgery or a medical emergency.

Ask your doctor how to adjust your insulin dose if needed. Do not change your medication dose or schedule without your doctor's advice.

If your doctor changes your brand, strength, or type of insulin, your dosage needs may change. Ask your pharmacist if you have any questions about the new kind of insulin you receive at the pharmacy.

Carry an ID card or wear a medical alert bracelet stating that you have diabetes, in case of emergency. Any doctor, dentist, or emergency medical care provider who treats you should know that you are diabetic.

Insulin is only part of a complete program of treatment that may also include diet, exercise, weight control, foot care, eye care, dental care, and testing your blood sugar. Follow your diet, medication, and exercise routines very closely. Changing any of these factors can affect your blood sugar levels.

Storing unopened vials and cartridges: Keep in the carton and store in a refrigerator, protected from light. Unopened vials may also be stored at room temperature, away from heat and bright light.

Storing after your first use: Keep the "in-use" vials or cartridges at room temperature.

Do not freeze insulin regular, and throw away the medication if it has become frozen.

Throw away any insulin not used before the expiration date on the medicine label.

What happens if I miss a dose?

Since insulin regular is used before meals or snacks, you may not be on a timed dosing schedule. Whenever you use insulin regular, be sure to eat a meal or snack within 15 to 30 minutes. Do not use extra insulin to make up a missed dose.

It is important to keep insulin regular on hand at all times. Get your prescription refilled before you run out of medicine completely.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An insulin overdose can cause life-threatening hypoglycemia.

Symptoms of severe hypoglycemia include extreme weakness, blurred vision, sweating, trouble speaking, tremors, stomach pain, confusion, and seizure (convulsions).

What should I avoid while using Novolin R PenFill (insulin regular)?

Do not change the brand of insulin regular or syringe you are using without first talking to your doctor or pharmacist. Avoid drinking alcohol. Your blood sugar may become dangerously low if you drink alcohol while using insulin regular.

Novolin R PenFill (insulin regular) side effects

Get emergency medical help if you have any of these signs of insulin allergy: itching skin rash over the entire body, wheezing, trouble breathing, fast heart rate, sweating, or feeling like you might pass out.

Hypoglycemia, or low blood sugar, is the most common side effect of insulin. Symptoms include headache, hunger, weakness, sweating, tremors, irritability, trouble concentrating, rapid breathing, fast heartbeat, fainting, or seizure (severe hypoglycemia can be fatal). Carry hard candy or glucose tablets with you in case you have low blood sugar.

Tell your doctor if you have itching, swelling, redness, or thickening of the skin where you inject insulin.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Novolin R PenFill (insulin regular)?

Using certain medicines can make it harder for you to tell when you have low blood sugar. Tell your doctor if you use any of the following:

• 
  

  albuterol (Proventil, Ventolin);

  
  


• 
  

  clonidine (Catapres);

  
  


• 
  

  reserpine; or

  
  


• 
  

  beta-blockers such as atenolol (Tenormin, Tenoretic), carvedilol (Coreg), labetalol (Normodyne, Trandate), metoprolol (Dutoprol, Lopressor, Toprol), nadolol (Corgard), propranolol (Inderal, InnoPran), sotalol (Betapace), and others.

  
  

These lists are not complete and there are many other medicines that can increase or decrease the effects of insulin on lowering your blood sugar. Tell your doctor about all medications you use. This includes prescription, over the counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Novolin R PenFill resources

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

• Humulin R MedFacts Consumer Leaflet (Wolters Kluwer)


• Humulin R Prescribing Information (FDA)


• Humulin R (Concentrated) MedFacts Consumer Leaflet (Wolters Kluwer)


• Novolin R Prescribing Information (FDA)

Compare Novolin R PenFill with other medications

• Diabetes, Type 1
• Diabetes, Type 2
• Diabetic Ketoacidosis
• Gestational Diabetes
• Growth Hormone Reserve Test
• Hyperkalemia
• Insulin Resistance Syndrome
• Nonketotic Hyperosmolar Syndrome

Where can I get more information?

• Your pharmacist can provide more information about insulin regular.

See also: Novolin R PenFill side effects (in more detail)

Magnesium Verla N Konz.

Magnesium Verla N Konz. may be available in the countries listed below.

Ingredient matches for Magnesium Verla N Konz.

Magnesium Hydrogen Aspartate

Magnesium Hydrogen Aspartate dihydrate (a derivative of Magnesium Hydrogen Aspartate) is reported as an ingredient of Magnesium Verla N Konz. in the following countries:

• Germany

International Drug Name Search

Alergidryl

Alergidryl may be available in the countries listed below.

Ingredient matches for Alergidryl

Chlorphenamine

Chlorphenamine maleate (a derivative of Chlorphenamine) is reported as an ingredient of Alergidryl in the following countries:

• Argentina

International Drug Name Search

Bleph-10 Drops

Pronunciation: sul-fa-SEE-ta-mide
Generic Name: Sulfacetamide
Brand Name: Bleph-10

Bleph-10 Drops are used for:

Treating eye infections caused by certain bacteria.

Bleph-10 Drops are a sulfonamide. It works by restricting the production of folic acid, which bacteria need for growth. This kills the bacteria.

Do NOT use Bleph-10 Drops if:

• you are allergic to any ingredient in Bleph-10 Drops


• you have had a severe allergic reaction (eg, severe rash, hives, difficulty breathing, dizziness) to any other sulfonamide medicine, such as acetazolamide, celecoxib, certain diuretics (eg, hydrochlorothiazide), glyburide, probenecid, sulfamethoxazole, valdecoxib, or zonisamide

Contact your doctor or health care provider right away if any of these apply to you.

Before using Bleph-10 Drops:

Some medical conditions may interact with Bleph-10 Drops. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have a discharge from your eye

Some MEDICINES MAY INTERACT with Bleph-10 Drops. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Silver-containing products because they may decrease Bleph-10 Drops's effectiveness

This may not be a complete list of all interactions that may occur. Ask your health care provider if Bleph-10 Drops may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Bleph-10 Drops:

Use Bleph-10 Drops as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• To use Bleph-10 Drops in the eye, first, wash your hands. Tilt your head back. Using your index finger, pull the lower eyelid away from the eye to form a pouch. Drop the medicine into the pouch and gently close your eyes. Immediately use your finger to apply pressure to the inside corner of the eyelid for 1 to 2 minutes. Do not blink. Remove excess medicine around your eye with a clean, dry tissue, being careful not to touch your eye. Wash your hands to remove any medicine that may be on them.


• To prevent germs from contaminating your medicine, do not touch the applicator tip to any surface, including the eye. Keep the container tightly closed.


• To clear up your infection completely, use Bleph-10 Drops for the full course of treatment. Keep using it even if you feel better in a few days.


• Bleph-10 Drops works best if it is taken at the same time each day.


• Continue to use Bleph-10 Drops even if you feel well. Do not miss any doses.


• If you miss a dose of Bleph-10 Drops, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Bleph-10 Drops.

Important safety information:

• Bleph-10 Drops only works against bacteria; it does not treat viral infections


• Be sure to use Bleph-10 Drops for the full course of treatment. If you do not, the medicine may not clear up your infection completely. The bacteria could also become less sensitive to this or other medicines. This could make the infection harder to treat in the future.


• Long-term or repeated use of Bleph-10 Drops may cause a second infection. Tell your doctor if signs of a second infection occur. Your medicine may need to be changed to treat this.


• Bleph-10 Drops should be used with extreme caution in CHILDREN younger than 2 months old; safety and effectiveness in these children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Bleph-10 Drops while you are pregnant. It is not known if Bleph-10 Drops are found in breast milk after use in the eye. Do not breast-feed while using Bleph-10 Drops.

Possible side effects of Bleph-10 Drops:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Mild irritation, stinging, or burning.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); fever, chills, or persistent sore throat; new or worsening eye discharge, inflammation, or pain; joint pain; red, swollen, or blistered skin; vision changes; yellowing of the eyes or skin.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Bleph-10 side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Bleph-10 Drops may be harmful if swallowed. Symptoms of ingestion may include change in the amount of urine; nausea; vomiting.

Proper storage of Bleph-10 Drops:

Store Bleph-10 Drops at room temperature, between 46 and 77 degrees F (8 and 25 degrees C). Store away from heat, moisture, and light. Do not freeze. Keep Bleph-10 Drops out of the reach of children and away from pets.

General information:

• If you have any questions about Bleph-10 Drops, please talk with your doctor, pharmacist, or other health care provider.


• Bleph-10 Drops are to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Bleph-10 Drops. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Bleph-10 resources

• Bleph-10 Side Effects (in more detail)
• Bleph-10 Dosage
• Bleph-10 Use in Pregnancy & Breastfeeding
• Bleph-10 Drug Interactions
• Bleph-10 Support Group
• 0 Reviews for Bleph-10 - Add your own review/rating

Compare Bleph-10 with other medications

• Conjunctivitis
• Trachoma