Glynase Tablets (Micronized)

Pronunciation: GLYE-bure-ide
Generic Name: Glyburide
Brand Name: Examples include Glycron and Glynase

Glynase Tablets (Micronized) are used for:

Treating type 2 diabetes. It is used along with diet and exercise. It may be used alone or with other antidiabetic medicines.

Glynase Tablets (Micronized) are a sulfonylurea antidiabetic medicine. It works by causing the pancreas to release insulin, which helps to lower blood sugar.

Do NOT use Glynase Tablets (Micronized) if:

• you are allergic to any ingredient in Glynase Tablets (Micronized)


• you have type 1 diabetes or certain severe problems associated with diabetes (eg, diabetic coma, diabetic ketoacidosis)


• you have moderate to severe burns or very high blood acid levels (acidosis)


• you are pregnant and are within 2 weeks of the expected delivery date


• you are taking bosentan

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

Before using Glynase Tablets (Micronized):

Some medical conditions may interact with Glynase Tablets (Micronized). 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 had a severe allergic reaction (eg, a severe rash, hives, itching, breathing difficulties, dizziness) to any other sulfonamide medicine, such as acetazolamide, celecoxib, certain diuretics (eg, hydrochlorothiazide), glipizide, probenecid, sulfamethoxazole, valdecoxib, or zonisamide


• if you have a history of liver, kidney, thyroid, or heart problems


• if you have stomach or bowel problems (eg, stomach or bowel blockage, stomach paralysis), drink alcohol, or have had poor nutrition


• if you have a certain nerve problem (autonomic neuropathy), very poor health, a high fever, a severe infection, severe diarrhea, or high blood acid levels, or have had a severe injury


• if you have a history of certain hormonal problems (eg, adrenal or pituitary problems, syndrome of inappropriate secretion of antidiuretic hormone [SIADH]), low blood sodium levels, anemia, or glucose-6-phosphate dehydrogenase (G6PD) deficiency


• if you will be having surgery

Some MEDICINES MAY INTERACT with Glynase Tablets (Micronized). Tell your health care provider if you are taking any other medicines, especially any of the following:

• Bosentan because liver problems may occur and the effectiveness of both medicines may be decreased


• Beta-blockers (eg, propranolol) because the risk of low blood sugar may be increased. They may also hide certain signs of low blood sugar and make it more difficult to notice


• Angiotensin-converting enzyme (ACE) inhibitors (eg, enalapril), anticoagulants (eg, warfarin), azole antifungals (eg, ketoconazole, miconazole), chloramphenicol, clarithromycin, clofibrate, disopyramide, fenfluramine, fluoxetine, insulin, monoamine oxidase inhibitors (MAOIs) (eg, phenelzine), nonsteroidal anti-inflammatory drugs (NSAIDs) (eg, ibuprofen), phenylbutazone, probenecid, quinolone antibiotics (eg, ciprofloxacin), salicylates (eg, aspirin), or sulfonamides (eg, sulfamethoxazole) because the risk of low blood sugar may be increased


• Calcium channel blockers (eg, diltiazem), corticosteroids (eg, prednisone), decongestants (eg, pseudoephedrine), diazoxide, diuretics (eg, furosemide, hydrochlorothiazide), estrogens, hormonal contraceptives (eg, birth control pills), hydantoins (eg, phenytoin), isoniazid, niacin, phenothiazines (eg, promethazine), rifamycins (eg, rifampin), sympathomimetics (eg, albuterol, epinephrine, terbutaline), or thyroid supplements (eg, levothyroxine) because they may decrease Glynase Tablets (Micronized)'s effectiveness, resulting in high blood sugar


• Gemfibrozil because blood sugar may be increased or decreased


• Cyclosporine because the risk of its side effects may be increased by Glynase Tablets (Micronized)

This may not be a complete list of all interactions that may occur. Ask your health care provider if Glynase Tablets (Micronized) 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 Glynase Tablets (Micronized):

Use Glynase Tablets (Micronized) as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Glynase Tablets (Micronized) by mouth with food as directed by your doctor.


• If you are taking 1 dose daily, take Glynase Tablets (Micronized) with breakfast or the first main meal of the day unless your doctor tells you otherwise.


• High amounts of dietary fiber may decrease Glynase Tablets (Micronized)'s effectiveness, resulting in high blood sugar. If you have questions about including fiber in your diet while you are taking Glynase Tablets (Micronized), talk with your doctor.


• Glynase Tablets (Micronized) works best if it is taken at the same time each day.


• Continue to take Glynase Tablets (Micronized) even if you feel well. Do not miss any doses.


• If you miss a dose of Glynase Tablets (Micronized), take 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 take 2 doses at once.

Ask your health care provider any questions you may have about how to use Glynase Tablets (Micronized).

Important safety information:

• Glynase Tablets (Micronized) may cause drowsiness, dizziness, blurred vision, or lightheadedness. These effects may be worse if you take it with alcohol or certain medicines. Use Glynase Tablets (Micronized) with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Do not drink large amounts of alcohol while you use Glynase Tablets (Micronized). Alcohol may increase the risk of Glynase Tablets (Micronized)'s side effects. Also, alcohol may rarely interact with Glynase Tablets (Micronized) and cause a serious reaction with symptoms such as flushing, nausea, vomiting, dizziness, or stomach pain. Talk with your doctor or health care provider before you drink alcohol while you use Glynase Tablets (Micronized).


• Carry an ID card at all times that says you have diabetes. Check your blood sugar levels as directed by your doctor. If they are often higher or lower than they should be and you take Glynase Tablets (Micronized) exactly as prescribed, tell your doctor.


• Proper diet, regular exercise, and regular blood sugar testing are important for best results with Glynase Tablets (Micronized). Follow the diet and exercise program given to you by your health care provider.


• It may be harder to control your blood sugar during times of stress such as fever, infection, injury, or surgery. Talk with your doctor about how to control your blood sugar if any of these occur. Do not change the dose of your medicine without checking with your doctor.


• Glynase Tablets (Micronized) may cause low blood sugar levels. Low blood sugar may make you anxious, sweaty, weak, dizzy, drowsy, or faint. It may also make your heart beat faster; make your vision change; give you a headache, chills, or tremors; or make you more hungry. It is a good idea to carry a reliable source of glucose (eg, tablets or gel) to treat low blood sugar. If this is not available, you should eat or drink a quick source of sugar like table sugar, honey, candy, orange juice, or non-diet soda. This will raise your blood sugar level quickly. Tell your doctor right away if this happens. To prevent low blood sugar, eat meals at the same time each day and do not skip meals.


• Risk of low blood sugar may be increased by severe or prolonged exercise, drinking alcohol, or skipping meals.


• Glynase Tablets (Micronized) are a sulfonylurea. It may increase the risk of death from heart disease. Talk with your doctor about the benefits and risks of this or other therapies to treat your condition.


• Glynase Tablets (Micronized) may cause you to become sunburned more easily. Avoid the sun, sunlamps, or tanning booths until you know how you react to Glynase Tablets (Micronized). Use a sunscreen or wear protective clothing if you must be outside for more than a short time.


• Do not change from this type of glyburide (micronized) to the nonmicronized type without checking with your doctor. Their effectiveness may not be the same.


• Glynase Tablets (Micronized) should not be used by itself to treat type 1 diabetes. If you have questions about using Glynase Tablets (Micronized) to treat type 1 diabetes, talk with our doctor.


• Tell your doctor or dentist that you take Glynase Tablets (Micronized) before you receive any medical or dental care, emergency care, or surgery.


• Lab tests, including fasting blood glucose and hemoglobin A_1C, may be performed while you use Glynase Tablets (Micronized). These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• Use Glynase Tablets (Micronized) with caution in the ELDERLY; they may be more sensitive to its effects, especially low blood sugar levels.


• Glynase Tablets (Micronized) should not be used in CHILDREN; safety and effectiveness in 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 Glynase Tablets (Micronized) while you are pregnant. If you take Glynase Tablets (Micronized) during pregnancy, do not take it within 2 weeks of the expected delivery date without first checking with your doctor. It is not known if Glynase Tablets (Micronized) are found in breast milk. Do not breast-feed while taking Glynase Tablets (Micronized).

When used for long periods of time, Glynase Tablets (Micronized) may not work as well. If your blood sugar has been under control and then becomes hard to manage, contact your doctor. Do not change the dose of your medicine without checking with your doctor.

Possible side effects of Glynase Tablets (Micronized):

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:

Feeling of stomach fullness; heartburn; nausea.

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

Severe allergic reactions (rash; hives; itching; difficulty breathing; joint or muscle pain, tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); blisters on the skin; confusion; fainting; fever, chills, or persistent sore throat; irregular heartbeat; low blood sugar symptoms (eg, anxiety, dizziness, drowsiness, fast heartbeat, headache, lightheadedness, tremors, unusual sweating, weakness); severe or persistent blurred vision or other vision problems; symptoms of liver problems (eg, dark urine, loss of appetite, pale stools, stomach pain, yellowing of the eyes or skin); unusual bruising or bleeding; unusual tiredness or weakness.

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: Glynases (Micronized) 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. Symptoms may include coma; confusion; fainting; fast heartbeat; lethargy; lightheadedness; seizures; severe dizziness or drowsiness; tremor; unusual sweating.

Proper storage of Glynase Tablets (Micronized):

Store Glynase Tablets (Micronized) at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Glynase Tablets (Micronized) out of the reach of children and away from pets.

General information:

• If you have any questions about Glynase Tablets (Micronized), please talk with your doctor, pharmacist, or other health care provider.


• Glynase Tablets (Micronized) 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 Glynase Tablets (Micronized). 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 Glynase Tablets (Micronized) resources

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

Compare Glynase Tablets (Micronized) with other medications

• Diabetes, Type 2

Glumetza

Generic Name: metformin (Oral route)

met-FOR-min hye-droe-KLOR-ide

Oral route(Tablet;Tablet, Extended Release;Solution)

Fortamet(R), Glucophage(R), Glucophage XR(R), Riomet(R): Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with metformin hydrochloride; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in association with pathophysiologic conditions, including diabetes mellitus, characterized by significant tissue hypoperfusion and hypoxemia. The risk of lactic acidosis increases with renal impairment, increased age, congestive heart failure, and hepatic insufficiency. Treatment with metformin should not be initiated in patients 80 years old or older, unless measurement of creatinine clearance demonstrates that renal function is normal. Therapy should temporarily be discontinued prior to any intravascular radiocontrast study or surgical procedure. Excessive alcohol use should be avoided, because alcohol potentiates the effects of metformin on lactate metabolism. Discontinue therapy immediately and institute supportive measures promptly for suspected lactic acidosis .

Oral route(Tablet, Extended Release)

Glumetza(R): Lactic acidosis is a rare, but serious, complication that can occur due to metformin accumulation. The risk of lactic acidosis increases with renal or hepatic impairment, acute congestive heart failure, sepsis, dehydration, and excess alcohol intake. Onset may be subtle and include nonspecific symptoms such as malaise, myalgia, respiratory distress, somnolence, and abdominal distress; laboratory abnormalities include low pH, increased anion gap and elevated blood lactate. If lactic acidosis is suspected, Glumetza(R) should be discontinued and the patient immediately hospitalized .

Commonly used brand name(s)

In the U.S.

• Fortamet


• Glucophage


• Glucophage XR


• Glumetza


• Riomet

Available Dosage Forms:

• Tablet


• Tablet, Extended Release


• Solution

Therapeutic Class: Hypoglycemic

Chemical Class: Metformin

Uses For Glumetza

Metformin is used to treat high blood sugar levels that are caused by a type of diabetes mellitus or sugar diabetes called type 2 diabetes. With this type of diabetes, insulin produced by the pancreas is not able to get sugar into the cells of the body where it can work properly. Using metformin alone, with a type of oral antidiabetic medicine called a sulfonylurea, or with insulin, will help to lower blood sugar when it is too high and help restore the way you use food to make energy.

Many people can control type 2 diabetes with diet and exercise. Following a specially planned diet and exercise will always be important when you have diabetes, even when you are taking medicines. To work properly, the amount of metformin you take must be balanced against the amount and type of food you eat and the amount of exercise you do. If you change your diet or exercise, you will want to test your blood sugar to find out if it is too low. Your doctor will teach you what to do if this happens.

Metformin does not help patients does not help patients who have insulin-dependent or type 1 diabetes because they cannot produce insulin from their pancreas gland. Their blood glucose is best controlled by insulin injections.

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

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although this use is not included in product labeling, metformin is used in certain patients with the following medical conditions:

• Polycystic ovary syndrome.

Before Using Glumetza

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 metformin oral solution and tablets in children 10 to 16 years of age. However, safety and efficacy of metformin extended-release tablets in the pediatric population have not been established.

Geriatric

Although appropriate studies on the relationship of age to the effects of metformin have not been performed in the geriatric population, geriatric-specific problems are not expected to limit the usefulness of metformin in the elderly. However, elderly patients are more likely to have age-related kidney problems, which may require caution in patients receiving metformin. This medicine is not recommended in patients 80 years of age and older who have kidney problems.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	B	Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate studies in pregnant women OR animal studies have shown an adverse effect, but adequate studies in pregnant women have failed to demonstrate a risk to the fetus.

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 not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Acetrizoic Acid


• Diatrizoate


• Ethiodized Oil


• Iobenzamic Acid


• Iobitridol


• Iocarmic Acid


• Iocetamic Acid


• Iodamide


• Iodipamide


• Iodixanol


• Iodohippuric Acid


• Iodopyracet


• Iodoxamic Acid


• Ioglicic Acid


• Ioglycamic Acid


• Iohexol


• Iomeprol


• Iopamidol


• Iopanoic Acid


• Iopentol


• Iophendylate


• Iopromide


• Iopronic Acid


• Ioseric Acid


• Iosimide


• Iotasul


• Iothalamate


• Iotrolan


• Iotroxic Acid


• Ioversol


• Ioxaglate


• Ioxitalamic Acid


• Ipodate


• Metrizamide


• Metrizoic Acid


• Tyropanoate Sodium

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.

• Acetazolamide


• Alatrofloxacin


• Balofloxacin


• Cimetidine


• Ciprofloxacin


• Clinafloxacin


• Dichlorphenamide


• Dofetilide


• Enoxacin


• Fleroxacin


• Flumequine


• Gatifloxacin


• Gemifloxacin


• Grepafloxacin


• Levofloxacin


• Lomefloxacin


• Moxifloxacin


• Norfloxacin


• Ofloxacin


• Pefloxacin


• Prulifloxacin


• Rufloxacin


• Sparfloxacin


• Temafloxacin


• Topiramate


• Tosufloxacin


• Trovafloxacin Mesylate


• Zonisamide

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.

• Acebutolol


• Alprenolol


• Atenolol


• Betaxolol


• Bevantolol


• Bisoprolol


• Bitter Melon


• Bucindolol


• Carteolol


• Carvedilol


• Celiprolol


• Cephalexin


• Clorgyline


• Dilevalol


• Enalaprilat


• Enalapril Maleate


• Esmolol


• Fenugreek


• Glucomannan


• Guar Gum


• Iproniazid


• Isocarboxazid


• Labetalol


• Levobunolol


• Mepindolol


• Metipranolol


• Metoprolol


• Moclobemide


• Nadolol


• Nebivolol


• Nialamide


• Oxprenolol


• Pargyline


• Penbutolol


• Phenelzine


• Pindolol


• Procarbazine


• Propranolol


• Psyllium


• Rifampin


• Selegiline


• Sotalol


• Talinolol


• Tertatolol


• Timolol


• Toloxatone


• Tranylcypromine


• Trospium

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.

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:

• Alcohol, excessive use or


• Underactive adrenal glands or


• Underactive pituitary gland or


• Undernourished condition or


• Weakened physical condition or


• Any other condition that causes low blood sugar—Patients with these conditions may be more likely to develop low blood sugar while taking metformin.

• Anemia (low levels of red blood cells) or


• Vitamin B12 deficiency—Use with caution. May make these conditions worse.

• Congestive heart failure, acute or unstable or


• Dehydration or


• Heart attack, acute or


• Hypoxemia (decreased oxygen in the blood) or


• Kidney disease or


• Liver disease or


• Sepsis (blood poisoning) or


• Shock (low blood pressure, blood circulation is poor)—A rare condition called lactic acidosis can occur. Talk with your doctor if you have concerns about this.

• Diabetic ketoacidosis (ketones in the blood) or


• Kidney disease, severe or


• Metabolic acidosis (extra acids in the blood) or


• Type 1 diabetes—Should not be used in patients with these conditions.

• Fever or


• Infection or


• Surgery or


• Trauma—These conditions may cause temporary problems with blood sugar control and your doctor may want to treat you with insulin.

Proper Use of metformin

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

This medicine usually comes with a patient information insert. Read the information carefully and make sure you understand it before taking this medicine. If you have any questions, ask your doctor.

Carefully follow the special meal plan your doctor gave you. This is a very important part of controlling your condition, and is necessary if the medicine is to work properly. Also, exercise regularly and test for sugar in your blood or urine as directed.

Metformin should be taken with meals to help reduce stomach or bowel side effects that may occur during the first few weeks of treatment.

Swallow the extended-release tablet whole with a full glass of water. Do not crush, break, or chew it.

While taking the extended-release tablet, part of the tablet may pass into your stool after your body has absorbed the medicine. This is normal and nothing to worry about.

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.

Use only the brand of this medicine that your doctor prescribed. Different brands may not work the same way.

You may notice improvement in your blood glucose control in 1 to 2 weeks, but the full effect of blood glucose control may take up to 2 to 3 months. Ask your doctor if you have any questions about this.

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 type 2 diabetes:
  
  • For oral dosage form (extended-release tablets):
    
    • Adults—
      
      • Metformin alone (Fortamet®): At first, 1000 milligrams (mg) once a day taken with the evening meal. Your doctor may increase your dose if needed until your blood sugar is controlled. However, the dose is usually not more than 2500 mg per day.
      
      
      • Metformin alone (Glucophage® XR): At first, 500 mg once daily with the evening meal. Your doctor may increase your dose if needed until your blood sugar is controlled. However, the dose is usually not more than 2000 mg per day.
      
      
      • Metformin alone (Glumetza®): At first, 500 mg once a day taken with the evening meal. Then, your doctor may increase your dose if needed until your blood sugar is controlled. However, the dose is usually not more than 2000 mg per day.
      
      
      • Metformin with a sulfonylurea: Your doctor will determine the dose of each medicine.
      
      
      • Metformin with insulin: At first, 500 mg once a day. Then, your doctor may increase your dose by 500 mg every week if needed until your blood sugar is controlled. However, the dose is usually not more than 2500 mg per day.
      
      
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For oral dosage form (solution):
    
    • Adults—
      
      • Metformin alone: At first, 5 milliliters (mL) two times a day, or 8.5 mL once a day with meals. Your doctor may increase your dose if needed until your blood sugar is controlled. However, the dose is usually not more than 25.5 mL per day.
      
      
      • Metformin with a sulfonylurea: Your doctor will determine the dose of each medicine.
      
      
      • Metformin with insulin: At first, 5 mL once a day. Your doctor may increase your dose if needed until your blood sugar is controlled. However, the dose is usually not more than 25 mL per day.
      
      
    
    
    • Children 10 to 16 years of age—At first, 5 mL two times a day with meals. Your doctor may increase your dose if needed until your blood sugar is controlled. However, the dose is usually not more than 20 mL per day.
    
    
    • Children younger than 10 years of age—Use and dose must be determined by your doctor.
    
    
  
  
  • For oral dosage form (tablets):
    
    • Adults—
      
      • Metformin alone: At first, 500 milligrams (mg) two times a day taken with the morning and evening meals, or 850 mg a day taken with the morning meal. Your doctor may increase your dose if needed until your blood sugar is controlled. Later, your doctor may want you to take 500 or 850 mg two to three times a day with meals. However, the dose is usually not more than 2550 mg per day.
      
      
      • Metformin with a sulfonylurea: Your doctor will determine the dose of each medicine.
      
      
      • Metformin with insulin: At first, 500 mg a day. Your doctor may increase your dose by 500 mg every week if needed until your blood sugar is controlled. However, the dose is usually not more than 2500 mg per day.
      
      
    
    
    • Children 10 to 16 years of age—At first, 500 mg two times a day taken with the morning and evening meals. Your doctor may increase your dose if needed until your blood sugar is controlled. However, the dose is usually not more than 2000 mg per day.
    
    
    • Children younger than 10 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 Glumetza

It is very important that your doctor check your progress at regular visits, especially during the first few weeks that you take this medicine. Blood and urine tests may be needed to check for unwanted effects.

This medicine may interact with the dye used for an X-ray or CT scan. Your doctor should advise you to stop taking it before you have any medical exams or diagnostic tests that might cause less urine output than usual. You may be advised to start taking the medicine again 48 hours after the exams or tests if your kidney function is tested and found to be normal.

Make sure any doctor or dentist who treats you knows that you are using this medicine. You may need to stop using this medicine several days before having surgery or medical tests.

It is very important to carefully follow any instructions from your health care team about:

• Alcohol—Drinking alcohol may cause severe low blood sugar. Discuss this with your health care team.


• Other medicines—Do not take other medicines unless they have been discussed with your doctor. This especially includes nonprescription medicines such as aspirin, and medicines for appetite control, asthma, colds, cough, hay fever, or sinus problems.


• Counseling—Other family members need to learn how to prevent side effects or help with side effects if they occur. Also, patients with diabetes may need special counseling about diabetes medicine dosing changes that might occur with lifestyle changes, such as changes in exercise or diet. Counseling on birth control and pregnancy may be needed because of the problems that can occur in pregnancy for patients with diabetes.


• Travel—Keep a recent prescription and your medical history with you. Be prepared for an emergency as you would normally. Make allowances for changing time zones and keep your meal times as close as possible to your usual meal times.


• In case of emergency—There may be a time when you need emergency help for a problem caused by your diabetes. You need to be prepared for these emergencies. It is a good idea to wear a medical identification (ID) bracelet or neck chain at all times. Also, carry an ID card in your wallet or purse that says that you have diabetes and a list of all of your medicines.

Under certain conditions, too much metformin can cause lactic acidosis. The symptoms of lactic acidosis are severe and quick to appear, and usually occur when other health problems not related to the medicine are present and are very severe, such as a heart attack or kidney failure. Symptoms of lactic acidosis include abdominal or stomach discomfort, decreased appetite; diarrhea; fast or shallow breathing; a general feeling of discomfort; severe muscle pain or cramping; and unusual sleepiness, tiredness, or weakness.

If symptoms of lactic acidosis occur, you should get immediate emergency medical help.

Metformin can cause low blood sugar (hypoglycemia). However, this can also occur if you delay or miss a meal or snack, drink alcohol, exercise more than usual, cannot eat because of nausea or vomiting, take certain medicines, or take metformin with another type of diabetes medicine. The symptoms of low blood sugar must be treated before they lead to unconsciousness (passing out). Different people feel different symptoms of low blood sugar. It is important that you learn which symptoms of low blood sugar you usually have so that you can treat it quickly.

Symptoms of hypoglycemia (low blood sugar) include anxiety; behavior change similar to being drunk; blurred vision; cold sweats; confusion; cool, pale skin; difficulty with thinking; drowsiness; excessive hunger; fast heartbeat; headache (continuing); nausea; nervousness; nightmares; restless sleep; shakiness; slurred speech; or unusual tiredness or weakness.

If symptoms of low blood sugar occur, eat glucose tablets or gel, corn syrup, honey, or sugar cubes; or drink fruit juice, non-diet soft drink, or sugar dissolved in water. Also, check your blood for low blood sugar. Glucagon is used in emergency situations when severe symptoms such as seizures (convulsions) or unconsciousness occur. Have a glucagon kit available, along with a syringe or needle, and know how to use it. The members of your household also should know how to use it.

High blood sugar (hyperglycemia) is another problem related to uncontrolled diabetes. Symptoms of mild high blood sugar appear more slowly than those of low blood sugar. These may include blurred vision; drowsiness; dry mouth; flushed, dry skin; fruit-like breath odor; increased urination (frequency and volume); ketones in the urine; loss of appetite; sleepiness; stomachache, nausea or vomiting; tiredness; troubled breathing (rapid and deep); unconsciousness; or unusual thirst.

High blood sugar may occur if you do not exercise as much as usual, have a fever or infection, do not take enough or skip a dose of your diabetes medicine, or overeat or do not follow your meal plan.

If symptoms of high blood sugar occur, check your blood sugar level and then call your doctor for instructions.

This medicine is only part of a complete program for controlling diabetes. It is important that you always eat a healthy diet, watch your weight, and get regular exercise.

Glumetza 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:

More common

• Abdominal or stomach discomfort


• cough or hoarseness


• decreased appetite


• diarrhea


• fast or shallow breathing


• fever or chills


• general feeling of discomfort


• lower back or side pain


• muscle pain or cramping


• painful or difficult urination


• sleepiness

Less common

• Anxiety


• blurred vision


• chest discomfort


• cold sweats


• coma


• confusion


• cool, pale skin


• depression


• difficult or labored breathing


• dizziness


• fast, irregular, pounding, or racing heartbeat or pulse


• feeling of warmth


• headache


• increased hunger


• increased sweating


• nausea


• nervousness


• nightmares


• redness of the face, neck, arms, and occasionally, upper chest


• seizures


• shakiness


• shortness of breath


• slurred speech


• tightness in the chest


• unusual tiredness or weakness


• wheezing

Rare

• Behavior change similar to being drunk


• difficulty with concentrating


• drowsiness


• lack or loss of strength


• restless sleep


• unusual sleepiness

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:

More common

• Acid or sour stomach


• belching


• bloated


• excess air or gas in the stomach or intestines


• full feeling


• heartburn


• indigestion


• loss of appetite


• metallic taste in the mouth


• passing of gas


• stomachache


• stomach upset or pain


• vomiting


• weight loss

Less common

• Abnormal stools


• bad, unusual, or unpleasant (after) taste


• change in taste


• difficulty with moving


• discoloration of the fingernails or toenails


• flu-like symptoms


• joint pain


• rash


• runny nose


• sneezing


• stuffy nose


• swollen joints

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: Glumetza 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 Glumetza resources

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

• Glumetza Prescribing Information (FDA)


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• Glucophage XR Extended-Release Tablets MedFacts Consumer Leaflet (Wolters Kluwer)


• Glucophage XR Prescribing Information (FDA)


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Compare Glumetza with other medications

• Diabetes, Type 2
• Insulin Resistance Syndrome

Zanidip 20 mg tablets

1. Name Of The Medicinal Product

ZANIDIP 20 mg film-coated tablets

2. Qualitative And Quantitative Composition

One tablet contains 20 mg of lercanidipine hydrochloride, which is equivalent to 18.8 mg of lercanidipine.

For excipients, see 6.1.

3. Pharmaceutical Form

Film-coated tablet.

Pink, circular, biconvex tablets, scored on one side.

4. Clinical Particulars

4.1 Therapeutic Indications

ZANIDIP is indicated for the treatment of mild to moderate essential hypertension.

4.2 Posology And Method Of Administration

The recommended dosage is 10 mg orally once a day at least 15 minutes before meals; the dose may be increased to 20 mg depending on the individual patient's response.

Dose titration should be gradual, because it may take about 2 weeks before the maximal antihypertensive effect is apparent.

Some individuals, not adequately controlled on a single antihypertensive agent, may benefit from the addition of ZANIDIP to therapy with a beta-adrenoceptor blocking drug (atenolol), a diuretic (hydrochlorothiazide) or an angiotensin converting enzyme inhibitor (captopril or enalapril).

Since the dose-response curve is steep with a plateau at doses between 20-30 mg, it is unlikely that efficacy will be improved by higher doses; whereas side effects may increase.

Use in the elderly: although the pharmacokinetic data and clinical experience suggest that no adjustment of the daily dosage is required, special care should be exercised when initiating treatment in the elderly.

Use in children: since there is no clinical experience in patients under the age of 18 years, use in children is not currently recommended.

Use in renal or hepatic dysfunction: special care should be exercised when treatment is commenced in patients with mild to moderate renal or hepatic dysfunction. Although the usually recommended dose schedule may be tolerated by these subgroups, an increase in dose to 20 mg daily must be approached with caution. The antihypertensive effect may be enhanced in patients with hepatic impairment and consequently an adjustment of the dosage should be considered.

ZANIDIP is not recommended for use in patients with severe hepatic impairment or in patients with severe renal impairment (GFR < 30 ml/min).

4.3 Contraindications

• Hypersensitivity to the active substance “lercanidipine“, to any dihydropyridine or to any of the excipients of the medicinal product.

• Pregnancy and lactation (see 4.6).

• Women of child-bearing potential unless effective contraception is used.

• Left ventricular outflow tract obstruction.

• Untreated congestive cardiac failure.

• Unstable angina pectoris.

• Severe renal or hepatic impairment.

• Within 1 month of a myocardial infarction.

• Co-administration with:

o strong inhibitors of CYP3A4 (see 4.5),

o cyclosporin (see 4.5),

o grapefruit juice (see 4.5).

4.4 Special Warnings And Precautions For Use

Special care should be exercised when ZANIDIP is used in patients with sick sinus syndrome (if a pacemaker is not in situ). Although hemodynamic controlled studies revealed no impairment of ventricular function, care is also required in patients with LV dysfunction. It has been suggested that some short-acting dihydropyridines may be associated with increased cardiovascular risk in patients with ischaemic heart disease. Although ZANIDIP is long-acting caution is required in such patients.

Some dihydropyridines may rarely lead to precordial pain or angina pectoris. Very rarely patients with pre-existing angina pectoris may experience increased frequency, duration or severity of these attacks. Isolated cases of myocardial infarction may be observed (see 4.8).

Use in renal or hepatic dysfunction: special care should be exercised when treatment is commenced in patients with mild to moderate renal or hepatic dysfunction. Although the usually recommended dose schedule may be tolerated by these subgroups, an increase in dose to 20 mg daily must be approached with caution. The antihypertensive effect may be enhanced in patients with hepatic impairment and consequently an adjustment of the dosage should be considered.

ZANIDIP is not recommended for use in patients with severe hepatic impairment or in patients with severe renal impairment (GFR < 30 ml/min) (see 4.2).

Alcohol should be avoided since it may potentiate the effect of vasodilating antihypertensive drugs (see 4.5).

Inducers of CYP3A4 like anticonvulsants (e.g. phenytoin, carbamazepine) and rifampicin may reduce lercanidipine's plasma levels and therefore the efficacy of lercanidipine may be less than expected (see 4.5).

1 tablet contains 60 mg lactose and therefore should not be administered to patients with Lapp lactase insufficiency, galactosaemia or glucose/galactose malabsorption syndrome.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Lercanidipine is known to be metabolised by the CYP3A4 enzyme and, therefore, inhibitors and inducers of CYP3A4 administered concurrently may interact with the metabolism and elimination of lercanidipine.

Co-prescription of ZANIDIP with inhibitors of CYP3A4 (e.g. ketoconazole, itraconazole, ritonavir, erythromycin, troleandomycin) should be avoided (see 4.3).

An interaction study with a strong CYP3A4 inhibitor, ketoconazole, has shown a considerable increase in plasma levels of lercanidipine (a 15-fold increase of the AUC and an 8-fold increase of the C_max for the eutomer S-lercanidipine).

Cyclosporin and lercanidipine should not be administered together (see 4.3).

Increased plasma levels of both lercanidipine and cyclosporin have been observed following concomitant administration. A study in young healthy volunteers has shown that when cyclosporin was administered 3 hours after the lercanidipine intake, the plasma levels of lercanidipine did not change, while the AUC of cyclosporin increased by 27%. However, the co-administration of ZANIDIP with cyclosporin has caused a 3-fold increase of the plasma levels of lercanidipine and a 21% increase of the cyclosporin AUC.

Lercanidipine should not be taken with grapefruit juice (see 4.3).

As for other dihydropyridines, lercanidipine is sensitive to inhibition of metabolism by grapefruit juice, with a consequent rise in its systemic availability and increased hypotensive effect.

When concomitantly administered at a dose of 20 mg with midazolam p.o. to elderly volunteers, lercanidipine's absorption was increased (by approximately 40%) and the rate of absorption was decreased (t_max was delayed from 1.75 to 3 hours). Midazolam concentrations were not modified.

Caution should be exercised when ZANIDIP is co-prescribed with other substrates of CYP3A4, like terfenadine, astemizole, class III antiarrhythmic drugs such as amiodarone, quinidine.

Co-administration of ZANIDIP with CYP3A4 inducers like anticonvulsants (e.g. phenytoin, carbamazepine) and rifampicin should be approached with caution since the antihypertensive effect may be reduced and blood pressure should be monitored more frequently than usual.

When ZANIDIP was co-administered with metoprolol, a β-blocker eliminated mainly by the liver, the bioavailability of metoprolol was not changed while that of lercanidipine was reduced by 50%. This effect may be due to the reduction in the hepatic blood flow caused by β-blockers and may therefore occur with other drugs of this class. Consequently, lercanidipine may be safely administered with beta-adrenoceptor blocking drugs, but dose adjustment may be required.

An interaction study with fluoxetine (an inhibitor of CYP2D6 and CYP3A4), conducted in volunteers of an age of 65 ± 7 years (mean ± s.d.), has shown no clinically relevant modification of the pharmacokinetics of lercanidipine.

Concomitant administration of cimetidine 800 mg daily does not cause significant modifications in plasma levels of lercanidipine, but at higher doses caution is required since the bioavailability and the hypotensive effect of lercanidipine may be increased.

Co-administration of 20 mg lercanidipine in patients chronically treated with β-methyldigoxin showed no evidence of pharmacokinetic interaction. Healthy volunteers treated with digoxin following dosing with 20 mg lercanidipine given fasted showed a mean increase of 33% in digoxin C_max, while AUC and renal clearance were not significantly modified. Patients on concomitant digoxin treatment should be closely monitored clinically for signs of digoxin toxicity.

When a dose of 20 mg of ZANIDIP was repeatedly co-administered with 40 mg of simvastatin, the AUC of lercanidipine was not significantly modified, while simvastatin's AUC increased by 56% and that of its active metabolite β-hydroxyacid by 28%. It is unlikely that such changes are of clinical relevance. No interaction is expected when lercanidipine is administered in the morning and simvastatin in the evening, as indicated for such drug.

The co-administration of 20 mg lercanidipine to healthy volunteers given fasted didnot alter the pharmacokinetics of warfarin.

ZANIDIP has been safely administered with diuretics and ACE inhibitors.

Alcohol should be avoided since it may potentiate the effect of vasodilating antihypertensive drugs (see 4.4).

4.6 Pregnancy And Lactation

Data for lercanidipine provide no evidence of a teratogenic effect in the rat and the rabbit and reproductive performance in the rat was unimpaired. Nevertheless, since there is no clinical experience with lercanidipine in pregnancy and lactation, and other dihydropyridine compounds have been found teratogenic in animals, ZANIDIP should not be administered during pregnancy or to women with child-bearing potential unless effective contraception is used. Because of high lipophilicity of lercanidipine, distribution in milk may be expected. Therefore, it should not be administered to nursing mothers.

4.7 Effects On Ability To Drive And Use Machines

Clinical experience with lercanidipine indicates that it is unlikely to impair a patient's ability to drive or use machinery. However, caution should be exercised because dizziness, asthenia, fatigue and rarely somnolence may occur.

4.8 Undesirable Effects

About 1.8% of treated patients experienced adverse reactions.

The table below shows the incidence of adverse drug reactions, at least possibly causally related, grouped by MedDRA System Organ Class classification, and ranked by frequency (uncommon, rare).

As shown in the table, the most commonly occurring adverse drug reactions reported in controlled clinical trials are headache, dizziness, peripheral oedema, tachycardia, palpitations, flushing, each occurring in less than 1% of patients.

MedDRA System Organ Class	Frequency	Preferred Terms
Immune System Disorders	Very rare (<1/10,000)	hypersensitivity
Psychiatric Disorders	Rare (>1/10,000 <1/1000)	somnolence
Nervous System Disorders	Uncommon (>1/1000 <1/100)	headache; dizziness
Cardiac Disorders	Rare (>1/10,000 <1/1000) Uncommon (>1/1000 <1/100)	angina pectoris tachycardia; palpitations
Vascular Disorders	Uncommon (>1/1000 <1/100) Very rare (<1/10,000)	flushing syncope
Gastrointestinal Disorders	Rare (>1/10,000 <1/1000)	nausea; dyspepsia; diarrhoea; abdominal pain; vomiting
Skin and Subcutaneous Tissue Disorders	Rare (>1/10,000 <1/1000)	rash
Musculoskeletal, Connective Tissue and Bone Disorders	Rare (>1/10,000 <1/1000)	myalgia
Renal and Urinary Disorders	Rare (>1/10,000 <1/1000)	polyuria
General Disorders and Administration Site Conditions	Uncommon (>1/1000 <1/100) Rare (>1/10,000 <1/1000)	oedema peripheral asthenia; fatigue

In post-marketing experience, from spontaneous reports the following undesirable effects were reported very rarely (<1/10,000): gingival hypertrophy, reversible increases in serum levels of hepatic transaminases, hypotension, urinary frequency and chest pain.

Some dihydropyridines may rarely lead to precordial pain or angina pectoris. Very rarely patients with pre-existing angina pectoris may experience increased frequency, duration or severity of these attacks. Isolated cases of myocardial infarction may be observed.

Lercanidipine does not appear to influence adversely blood sugar or serum lipid levels.

4.9 Overdose

In the post-marketing experience, three cases of overdose were reported (150 mg, 280 mg and 800 mg of lercanidipine, respectively, ingested in an attempt to commit suicide).

Dose level	Signs/Symptoms	Management	Outcome
150 mg + undefined amount of alcohol	Sleepiness	Gastric lavage Active charcoal	Recovered
280 mg + 5.6 mg moxonidine	Cardiogenic shock Severe myocardial ischaemia Mild renal failure	High-dose catecholamines Furosemide Digitalis Parenteral plasma expanders	Recovered
800 mg	Emesis Hypotention	Active charcoal Cathartics Dopamine i.v.	Recovered

As with other dihydropyridines, overdosage might be expected to cause excessive peripheral vasodilatation with marked hypotension and reflex tachycardia. In case of severe hypotension, bradycardia and unconsciousness, cardiovascular support could be helpful, with intravenous atropine for bradycardia.

In view of the prolonged pharmacological effect of lercanidipine, it is essential that the cardiovascular status of patients who take an overdose is monitored for 24 hours at least. There is no information on the value of dialysis. Since the drug is highly lipophilic, it is most probable that plasma levels are no guide to the duration of the period of risk and dialysis may not be effective.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group:

Selective calcium channel blockers with mainly vascular effects

ATC code: C08CA13

Lercanidipine is a calcium antagonist of the dihydropyridine group and inhibits the transmembrane influx of calcium into cardiac and smooth muscle. The mechanism of its antihypertensive action is due to a direct relaxant effect on vascular smooth muscle thus lowering total peripheral resistance. Despite its short pharmacokinetic plasma half-life, lercanidipine is endowed with a prolonged antihypertensive activity because of its high membrane partition coefficient, and is devoid of negative inotropic effects due to its high vascular selectivity.

Since the vasodilatation induced by ZANIDIP is gradual in onset, acute hypotension with reflex tachycardia has rarely been observed in hypertensive patients.

As for other asymmetric 1,4-dihydropyridines, the antihypertensive activity of lercanidipine is mainly due to its (S)-enantiomer.

In addition to the clinical studies conducted to support the therapeutic indications, a further small uncontrolled but randomised study of patients with severe hypertension (mean + SD diastolic blood pressure of 114.5 + 3.7 mmHg) showed that blood pressure was normalised in 40% of the 25 patients on 20 mg once daily dose and in 56% of 25 patients on 10 mg twice daily doses of ZANIDIP. In a double-blind, randomized, controlled study versus placebo in patients with isolated systolic hypertension ZANIDIP was efficacious in lowering systolic blood pressure from mean initial values of 172.6 + 5.6 mmHg to 140.2 + 8.7 mmHg.

5.2 Pharmacokinetic Properties

ZANIDIP is completely absorbed after 10-20 mg oral administration and peak plasma levels, 3.30 ng/ml + 2.09 s.d. and 7.66 ng/ml + 5.90 s.d. respectively, occur about 1.5-3 hours after dosing.

The two enantiomers of lercanidipine show a similar plasma level profile: the time to peak plasma concentration is the same, the peak plasma concentration and AUC are, on average, 1.2-fold higher for the (S) enantiomer and the elimination half-lives of the two enantiomers are essentially the same. No "in vivo" interconversion of enantiomers is observed.

Due to the high first pass metabolism, the absolute bioavailability of ZANIDIP orally administered to patients under fed conditions is around 10%, although it is reduced to 1/3 when administered to healthy volunteers under fasting conditions.

Oral availability of lercanidipine increases 4-fold when ZANIDIP is ingested up to 2 hours after a high fat meal. Accordingly, ZANIDIP should be taken before meals.

Distribution from plasma to tissues and organs is rapid and extensive.

The degree of serum protein binding of lercanidipine exceeds 98%. Since plasma protein levels are reduced in patients with severe renal or hepatic dysfunction, the free fraction of the drug may be increased.

ZANIDIP is extensively metabolised by CYP3A4; no parent drug is found in the urine or the faeces. It is predominantly converted to inactive metabolites and about 50% of the dose is excreted in the urine.

“In vitro” experiments with human liver microsomes have demonstrated that lercanidipine shows some degree of inhibition of CYP3A4 and CYP2D6, at concentrations 160- and 40-fold, respectively, higher than those reached at peak in the plasma after the dose of 20 mg.

Moreover, interaction studies in humans have shown that lercanidipine did not modify the plasma levels of midazolam, a typical substrate of CYP3A4, or of metoprolol, a typical substrate of CYP2D6. Therefore, inhibition of biotransformation of drugs metabolised by CYP3A4 and CYP2D6 by ZANIDIP is not expected at therapeutic doses.

Elimination occurs essentially by biotransformation.

A mean terminal elimination half life of 8-10 hours was calculated and the therapeutical activity lasts for 24 hours because of its high binding to lipid membrane. No accumulation was seen upon repeated administration.

Oral administration of ZANIDIP leads to plasma levels of lercanidipine not directly proportional to dosage (non-linear kinetics). After 10, 20 or 40 mg, peak plasma concentrations observed were in the ratio 1:3:8 and areas under plasma concentration-time curves in the ratio 1:4:18, suggesting a progressive saturation of first pass metabolism. Accordingly, availability increases with dosage elevation.

In elderly patients and in patients with mild to moderate renal dysfunction or mild to moderate hepatic impairment the pharmacokinetic behaviour of lercanidipine was shown to be similar to that observed in the general patient population; patients with severe renal dysfunction or dialysis-dependent patients showed higher levels (about 70%) of the drug. In patients with moderate to severe hepatic impairment, the systemic bioavailability of lercanidipine is likely to be increased since the drug is normally metabolised extensively in the liver.

5.3 Preclinical Safety Data

Safety pharmacological studies in animals have shown no effects on the autonomic nervous system, the central nervous system or on gastrointestinal function at antihypertensive doses.

The relevant effects which have been observed in long-term studies in rats and dogs were related, directly or indirectly, to the known effects of high doses of Ca-antagonists, predominantly reflecting exaggerated pharmacodynamic activity.

Lercanidipine was not genotoxic and showed no evidence of carcinogenic hazard.

Fertility and general reproductive performance in rats were unaffected by treatment with lercanidipine.

There was no evidence of any teratogenic effect in rats and rabbits; however, in rats, lercanidipine at high dose levels induced pre- and post- implantation losses and delay in foetal development.

Lercanidipine hydrochloride, when administered at high dose (12 mg/kg/day) during labour, induced dystocia.

The distribution of lercanidipine and/or its metabolites in pregnant animals and their excretion in breast milk have not been investigated.

Metabolites have not been evaluated separately in toxicity studies.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Tablet core:

Lactose monohydrate

Microcrystalline cellulose

Sodium starch glycolate

Povidone K30

Magnesium stearate

Film coating:

Hypromellose

Talc

Titanium dioxide (E171)

Macrogol 6000

Ferric oxide (E172)

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

3 years.

6.4 Special Precautions For Storage

Store in the original package.

6.5 Nature And Contents Of Container

Aluminium/opaque PVC blisters.

Packs of 7, 14, 28, 35, 42, 50, 56, 98 and 100 tablets.*

6.6 Special Precautions For Disposal And Other Handling

No special requirements.

7. Marketing Authorisation Holder

RECORDATI Industria Chimica e Farmaceutica S.p.A. - Via Matteo Civitali, 1 - 20148 Milan, ITALY.

8. Marketing Authorisation Number(S)

PL04595/0010

9. Date Of First Authorisation/Renewal Of The Authorisation

9 August 2002

10. Date Of Revision Of The Text

April 2006

* Not all pack sizes may be marketed.

Propacet 100

Generic Name: acetaminophen and propoxyphene (a SEET a MIN oh fen and proe POX i feen)

Brand Names: Balacet, Darvocet A500, Darvocet-N 100, Darvocet-N 50, Propacet 100

What is Propacet 100 (acetaminophen and propoxyphene)?

Acetaminophen and propoxyphene was withdrawn from the U.S. market in November 2010.

Propoxyphene is in a group of drugs called narcotic pain relievers.

Acetaminophen is a less potent pain reliever and a fever reducer that increases the effects of propoxyphene.

The combination of acetaminophen and propoxyphene is used to relieve mild to moderate pain with or without fever.

Acetaminophen and propoxyphene may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Propacet 100 (acetaminophen and propoxyphene)?

Acetaminophen and propoxyphene was withdrawn from the U.S. market in November 2010.

Propoxyphene may be habit-forming and should be used only by the person it was prescribed for. Keep the medication in a secure place where others cannot get to it. Do not use acetaminophen and propoxyphene if you have taken an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) in the last 14 days. Serious, life threatening side effects can occur if you use acetaminophen and propoxyphene before the MAO inhibitor has cleared from your body.

What should I discuss with my healthcare provider before taking Propacet 100 (acetaminophen and propoxyphene)?

Do not use this medication if you are allergic to acetaminophen (Tylenol) or propoxyphene. Propoxyphene may be habit-forming and should be used only by the person it was prescribed for. Never share this medication with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it. Do not use acetaminophen and propoxyphene if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days. A dangerous drug interaction could occur, leading to serious side effects.

To make sure you can safely take acetaminophen and propoxyphene, tell your doctor if you have any of these other conditions:

• 
  

  asthma, COPD, sleep apnea, or other breathing disorders;

  
  


• liver or kidney disease;


• 
  

  a history of head injury or brain tumor;

  
  


• 
  

  a gallbladder or pancreas disorder;

  
  


• 
  

  a stomach or intestinal disorder;

  
  


• 
  

  suicidal thoughts or behavior; or

  
  


• 
  

  mental illness, or a history of drug or alcohol addiction.

  
  

Tell your doctor if you drink more than three alcoholic beverages per day or if you have ever had alcoholic liver disease (cirrhosis). You may not be able to take medication that contains acetaminophen.

FDA pregnancy category C. It is not known whether this medication is harmful to an unborn baby, but it could cause breathing problems or addiction/withdrawal symptoms in a newborn. Tell your doctor if you are pregnant or plan to become pregnant during treatment. Acetaminophen and propoxyphene can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take Propacet 100 (acetaminophen and propoxyphene)?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label. Tell your doctor if the medicine seems to stop working as well in relieving your pain.

An overdose of acetaminophen can damage your liver. Adults should not take more than 1 gram (1000 mg) of acetaminophen per dose or 4 grams (4000 mg) per day. If you drink more than three alcoholic beverages per day, you should never use more than 2 grams (2000 mg) of acetaminophen per day. Do not stop using acetaminophen and propoxyphene suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to avoid withdrawal symptoms when you stop using acetaminophen and propoxyphene. If you need surgery, tell the surgeon ahead of time that you are using acetaminophen and propoxyphene. You may need to stop using the medicine for a short time. Store at room temperature away from moisture and heat. Keep track of the amount of medicine used from each new bottle. Propoxyphene is a drug of abuse and you should be aware if anyone is using your medicine improperly or without a prescription.

What happens if I miss a dose?

Since acetaminophen and propoxyphene is taken as needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of acetaminophen and propoxyphene can be fatal.

Overdose symptoms may include extreme drowsiness, nausea, vomiting, dark urine, jaundice (yellowing of the skin or eyes), pinpoint or dilated pupils, confusion, seizure (convulsions), cold and clammy skin, blue lips, weak pulse, slow or uneven heart rate, shallow breathing, fainting, or breathing that stops.

What should I avoid while taking Propacet 100 (acetaminophen and propoxyphene)?

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Ask a doctor or pharmacist before using any other cold, allergy, pain, or sleep medication. Acetaminophen (sometimes abbreviated as "APAP") is contained in many combination medicines. Taking certain products together can cause you to get too much acetaminophen. Check the label to see if a medicine contains acetaminophen or APAP. Drinking alcohol can increase certain side effects of acetaminophen and propoxyphene.

Propacet 100 (acetaminophen and propoxyphene) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have a serious side effect such as:

• 
  

  shallow breathing, slow heartbeat, feeling like you might pass out;

  
  


• 
  

  chest pain, feeling short of breath;

  
  


• 
  

  confusion, unusual thoughts or behavior;

  
  


• 
  

  seizure (convulsions); or

  
  


• 
  

  nausea, stomach pain, loss of appetite, itching, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

  
  

Less serious side effects include:

• 
  

  feeling dizzy or drowsy;

  
  


• 
  

  mild nausea, vomiting, upset stomach, constipation;

  
  


• 
  

  headache, blurred vision; or

  
  


• 
  

  dry mouth.

  
  

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 Propacet 100 (acetaminophen and propoxyphene)?

Cold or allergy medicine, sleeping pills, muscle relaxers, antidepressants, or seizure medication can add to sleepiness caused by propoxyphene, or could slow your breathing. Tell your doctor if you regularly use any of these medicines, or any other narcotic medications.

Tell your doctor about all other medications you use, especially:

• 
  

  aspirin or a blood thinner such as warfarin (Coumadin);

  
  


• 
  

  birth control pills;

  
  


• 
  

  dexamethasone (Decadron, Hexadrol);

  
  


• 
  

  a diuretic (water pill) such as furosemide (Lasix);

  
  


• 
  

  St. John's wort;

  
  


• 
  

  an antibiotic such as clarithromycin (Biaxin), erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin), rifabutin (Mycobutin), rifampin (Rifadin, Rifater, Rifamate), or rifapentine (Priftin);

  
  


• 
  

  an antidepressant such as nefazodone;

  
  


• 
  

  antifungal medication such as fluconazole (Diflucan), itraconazole (Sporanox), ketoconazole (Nizoral), or voriconazole (Vfend);

  
  


• 
  

  a barbiturate such as phenobarbital (Solfoton);

  
  


• 
  

  heart or blood pressure medication such as amiodarone (Cordarone, Pacerone), diltiazem (Cartia, Cardizem), nifedipine (Nifedical, Procardia), propranolol (Inderal), verapamil (Calan, Covera, Isoptin, Verelan), and others;

  
  


• 
  

  HIV or AIDS medicine such as fosamprenavir (Lexiva), nelfinavir (Viracept), ritonavir (Norvir), zidovudine (Retrovir), and others; or

  
  


• 
  

  seizure medication such as carbamazepine (Carbatrol, Tegretol), lamotrigine (Lamictal), phenytoin (Dilantin), and others.

  
  

This list is not complete and there are many other drugs that can interact with acetaminophen and propoxyphene. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

More Propacet 100 resources

• Propacet 100 Side Effects (in more detail)
• Propacet 100 Use in Pregnancy & Breastfeeding
• Drug Images
• Propacet 100 Drug Interactions
• Propacet 100 Support Group
• 0 Reviews for Propacet00 - Add your own review/rating

• Darvocet A500 Prescribing Information (FDA)


• Darvocet A500 Advanced Consumer (Micromedex) - Includes Dosage Information


• Darvocet-N 100 MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Propacet 100 with other medications

• Pain

Where can I get more information?

• Your pharmacist can provide more information about acetaminophen and propoxyphene.

See also: Propacet00 side effects (in more detail)

Procoralan

Procoralan5mg

ivabradine film-coated tablets

Procoralan7.5mg

ivabradine film-coated tablets

Read all of this leaflet carefully before you start taking this medicine.

• Keep this leaflet. You may need to read it again.


• If you have any further questions, ask your doctor or pharmacist.


• This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.


• If any of the side effects gets serious, or if you notice side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

• 
  1. What Procoralan is and what it is used for


• 
  2. Before you take Procoralan


• 
  3. How to take Procoralan


• 
  4. Possible side effects


• 
  5. How to store Procoralan


• 
  6. Further information

What Procoralan Is And What It Is Used For

Procoralan is a heart medicine used to treat stable angina pectoris which causes chest pain.

It is used in patients who do not tolerate or cannot take heart medicines called beta-blockers. It is also used in combination with beta-blockers in patients whose condition is not fully controlled with a beta-blocker and whose heart rate is over 60 beats per minute.

About stable angina pectoris (usually referred to as “angina”):

Stable angina is a heart disease which happens when the heart does not receive enough oxygen. It usually appears between 40 and 50 years of age. The most common symptom of angina is chest pain or discomfort. Angina is more likely to happen when the heart beats faster in situations such as exercise, emotion, exposure to the cold or after eating. This increase in heart rate can cause the chest pain in people who suffer from angina.

How does Procoralan work?

Procoralan mainly works by reducing the heart rate by a few beats per minute. This lowers the heart’s need for oxygen especially in the situations when an angina attack is more likely to happen. In this way Procoralan helps to control and reduce the number of angina attacks.

Before You Take Procoralan

Do not take Procoralan:

• if you are allergic (hypersensitive) to ivabradine or any of the other ingredients of Procoralan;


• if your resting heart rate before treatment is too slow (below 60 beats per minute);


• if you are suffering from cardiogenic shock (a heart condition treated in hospital);


• if you suffer from a heart rhythm disorder;


• if you are having a heart attack;


• if you suffer from very low blood pressure;


• if you suffer from unstable angina (a severe form in which chest pain occurs very frequently and with or without exertion);


• if you suffer from severe heart failure (when your heart fails to work properly);


• if you have a pacemaker;


• if you suffer from severe liver problems;


• if you are already taking medicines for the treatment of fungal infections (such as ketoconazole, itraconazole), macrolide antibiotics (such as josamycin, clarithromycin, telithromycin or erythromycin given orally), medicines to treat HIV infections (such as nelfinavir, ritonavir) or nefazodone (medicine to treat depression) (see “Taking other medicines”);


• if you are pregnant;


• if you are breast-feeding.

Take special care with Procoralan:

• if you suffer from a heart rhythm disorder,


• if you have symptoms such as tiredness or shortness of breath (this could mean that your heart is slowing down too much),


• if you are already taking diltiazem, verapamil,


• if you are taking QT prolonging medicines to treat either heart rhythm disorders or other conditions (see the products listed in “Taking other medicines”),


• if you suffer from sustained atrial fibrillation (a type of irregular heartbeat),


• if you have had a recent stroke (cerebral attack),


• if you suffer from mild to moderate low blood pressure,


• if you suffer from chronic heart failure (when your heart fails to work properly),


• if you suffer from chronic retinal disease,


• if you suffer from moderate liver problems,


• if you suffer from severe renal problems.

If any of the above applies to you, talk to your doctor before or while taking Procoralan.

Taking other medicines:

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Make sure to tell your doctor if you are taking any of the following medicines, as a dose adjustment of Procoralan or monitoring should be required:

• diltiazem, verapamil (for high blood pressure or angina pectoris)


• fluconazole (an antifungal agent)


• rifampicin (an antibiotic)


• barbiturates (for difficult sleeping or epilepsy)


• phenytoin (for epilepsy)


• 
  Hypericum perforatum or St John’s Wort (herbal treatment for depression)


• QT prolonging medicines to treat either heart rhythm disorders or other conditions such as :
  
  
  • quinidine, disopyramide, ibutilide, sotalol, amiodarone (to treat heart rhythm disorders)
  • bepridil (to treat angina pectoris)
  • certain types of medicines to treat anxiety, schizophrenia or other psychoses (such as pimozide, ziprasidone, sertindole)
  • anti-malarial medicines (such as mefloquine or halofantrine)
  • erythromycin IV (an antibiotic)
  • pentamidine (an antiparasitic medicine)
  • cisapride (against the gastro-oesophageal reflux)

Taking Procoralan with food and drink:

Limit your consumption of grapefruit juice during treatment with Procoralan.

Pregnancy and breast-feeding:

Do not take Procoralan if you are pregnant or planning a pregnancy (see “Do not take Procoralan”).

If you are pregnant and have taken Procoralan, talk to your doctor.

Do not take Procoralan if you are breast-feeding (see “Do not take Procoralan”).

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines:

Procoralan may cause temporary luminous visual phenomena (see “4. Possible side effects”). If this happens to you, be careful when driving or using machines at times when there could be sudden changes in light intensity, especially when driving at night.

Important information about some of the ingredients of Procoralan:

Procoralan contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

How To Take Procoralan

Always take Procoralan exactly as your doctor has told you.

You should check with your doctor or pharmacist if you are not sure. The usual recommended starting dose is 1 tablet of Procoralan 5 mg twice daily increasing if necessary to 1 tablet of Procoralan 7.5 mg twice daily. Your doctor will decide the right dose for you. The usual dose is one tablet in the morning and one tablet in the evening. In some cases (e.g. if you are elderly), your doctor may prescribe half the dose i.e., one half 5 mg tablet of Procoralan 5 mg (corresponding to 2.5 mg ivabradine) in the morning and one half 5 mg tablet in the evening.

Procoralan should be taken during meals.

If you think that the effect of Procoralan is too strong or too weak, talk to your doctor or pharmacist.

Procoralan is not intended for use in children and adolescents younger than 18 years.

If you take more Procoralan than you should:

A large dose of Procoralan could make you feel breathless or tired because your heart slows down too much. If this happens, contact your doctor immediately.

If you forget to take Procoralan:

If you forget to take a dose of Procoralan, take the next dose at the usual time. Do not take a double dose to make up for the forgotten dose.

The calendar printed on the blister containing the tablets should help you remember when you last took a tablet of Procoralan.

If you stop taking Procoralan:

As the treatment for angina is usually life-long, you should discuss with your doctor before stopping this medicinal product.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

Procoralan Side Effects

Like all medicines, Procoralan can cause side effects, although not everybody gets them.

Very common side effects (more than 1 in 10 patients) reported with Procoralan are luminous visual phenomena (brief moments of increased brightness, most often caused by sudden changes in light intensity). Other common side effects (more than 1 in 100 patients but less than 1 in 10 patients) include affecting the way the heart works (the symptoms are a slowing down of the heart rate), headache, dizziness, blurred vision and palpitations and cardiac extra beats which are uncommon (more than 1 in 1000 patients but less than 1 in 100 patients). Also nausea, constipation, diarrhoea, vertigo, dyspnoea, muscle cramps and changes in laboratory parameters (blood tests) were reported uncommonly.

If any of the side effects gets serious or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

How To Store Procoralan

This medicinal product does not require any special storage conditions.

Keep out of the reach and sight of children.

Do not use Procoralan after the expiry date which is stated on the carton and blister. The expiry date refers to the last day of that month.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Further Information

What Procoralan contains:

• The active substance is ivabradine (as hydrochloride).
  Procoralan 5 mg: one film-coated tablet contains 5 mg ivabradine (equivalent to 5.390 mg ivabradine hydrochloride).
  
  Procoralan 7.5 mg: one film-coated tablet contains 7.5 mg ivabradine (equivalent to 8.085 mg ivabradine hydrochloride).


• The other ingredients in the tablet core are: lactose monohydrate, magnesium stearate (E 470 B), maize starch, maltodextrin, colloidal anhydrous silica (E 551), and in the tablet coating: hypromellose (E 464), titanium dioxide (E 171), macrogol 6000, glycerol (E 422), magnesium stearate (E 470 B), yellow iron oxide (E 172), red iron oxide (E 172).

What Procoralan looks like and contents of the pack:

Procoralan 5 mg tablets are salmon-coloured, oblong film-coated tablets scored on both sides, engraved with “5” on one face and Servier logo on the other.

Procoralan 7.5 mg tablets are salmon-coloured, triangular, film-coated tablets engraved with “7.5” on one face and Servier logo on the other.

The tablets are available in calendar packs (blisters) of 14, 28, 56, 84, 98, 100 or 112 tablets.

Not all pack sizes may be available.

Marketing Authorisation Holder and Manufacturer:

Marketing Authorisation Holder:

Les Laboratoires Servier

22, rue Garnier

92200 Neuilly-sur-Seine

France

Manufacturer:

Servier (Ireland) Industries Ltd

Gorey Road

Arklow – Co. Wicklow

Ireland

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

United Kingdom

Servier Laboratories Ltd

Tel: +44 (0)1 753 666409

This leaflet was last approved in January 2010.

Detailed information on this medicine is available on the European Medicines Agency (EMA) web site: http://www.ema.europa.eu