Pack Article Directory Curaçao: March 2012

Friday 30 March 2012

Nyquil Cold & Flu

Generic Name: acetaminophen, dextromethorphan, and doxylamine (a SEET a MIN oh fen, DEX tro me THOR fan, and dox IL a meen)

Brand Names: All-Nite, Coricidin HBP Nighttime Multi-Symptom Cold, Cough & Sore Throat Nighttime, Delsym Nighttime Cough & Cold, Multi-Symptom Nighttime Cold & Flu Relief, Multi-Symptom Nighttime Cold & Flu Relief (cherry), Night Time Cold/Flu, Nite Time Cold & Flu, Nite Time Cold & Flu Relief, Nyquil Cold & Flu, NyQuil Cold/Flu Relief, NyQuil Cold/Flu Relief Cherry, Tylenol Cold & Cough Nighttime Cool Burst, Tylenol Cough & Sore Throat Night Time, Tylenol Warming Cough & Sore Throat Nightime

What is Nyquil Cold & Flu (acetaminophen, dextromethorphan, and doxylamine)?

Acetaminophen is a pain reliever and fever reducer.

Doxylamine is an antihistamine that reduces the effects of the natural chemical histamine in the body. Histamine can produce symptoms of sneezing, itching, watery eyes, and runny nose.

Dextromethorphan is a cough suppressant. It affects the cough reflex in the brain that triggers coughing.

The combination of acetaminophen, doxylamine, and dextromethorphan is used to treat headache, fever, body aches, cough, runny nose, sneezing, itching, and watery eyes caused by allergies, the common cold, or the flu.

This medicine will not treat a cough that is caused by smoking, asthma, or emphysema.

Acetaminophen, doxylamine, and dextromethorphan may also be used for purposes not listed in this medication guide.

What is the most important information I should know about this medicine?

Do not take more of this medication than is recommended. An overdose of acetaminophen can damage your liver or cause death. Do not take this medication without a doctor's advice if you have ever had alcoholic liver disease (cirrhosis) or if you drink more than 3 alcoholic beverages per day. You should not use this medicine if you have severe constipation, a blockage in your stomach or intestines, or if you are unable to urinate. Do not use this medicine if you have untreated or uncontrolled diseases such as glaucoma, asthma or COPD, high blood pressure, heart disease, coronary artery disease, or overactive thyroid. Do not use this medicine 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. Avoid drinking alcohol. It may increase your risk of liver damage while you are taking acetaminophen, and can increase certain side effects of doxylamine. 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 which can lead to a fatal overdose. Check the label to see if a medicine contains acetaminophen or APAP.

What should I discuss with my healthcare provider before taking this medicine?

You should not use this medicine if you have severe constipation, a blockage in your stomach or intestines, or if you are unable to urinate. Do not use this medicine if you have untreated or uncontrolled diseases such as glaucoma, asthma or COPD, high blood pressure, heart disease, coronary artery disease, or overactive thyroid. Do not use this medicine 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.

Ask a doctor or pharmacist if it is safe for you to take this medicine if you have:

liver disease, cirrhosis, a history of alcoholism, or if you drink more than 3 alcoholic beverages per day;

a blockage in your digestive tract (stomach or intestines);

kidney disease;

cough with mucus, or cough caused by emphysema or chronic bronchitis;

enlarged prostate or urination problems; or

if you take potassium (Cytra, Epiklor, K-Lyte, K-Phos, Kaon, Klor-Con, Polycitra, Urocit-K).

It is not known whether acetaminophen, doxylamine, and dextromethorphan will harm an unborn baby. Do not use this medicine without a doctor's advice if you are pregnant. Acetaminophen, doxylamine, and dextromethorphan may pass into breast milk and may harm a nursing baby. Antihistamines may also slow breast milk production. Do not use this medicine without a doctor's advice if you are breast-feeding a baby.

Artificially sweetened cold medicine may contain phenylalanine. If you have phenylketonuria (PKU), check the medication label to see if the product contains phenylalanine.

How should I take this medicine?

Use exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. This medicine is usually taken only for a short time until your symptoms clear up.

Do not take more of this medication than is recommended. An overdose of acetaminophen can damage your liver or cause death. Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children.

Measure liquid medicine with a special dose measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose measuring device, ask your pharmacist for one.

Do not take for longer than 7 days in a row. Stop taking the medicine and call your doctor if you still have a fever after 3 days of use, you still have pain after 7 days (or 5 days if treating a child), if your symptoms get worse, or if you have a skin rash, ongoing headache, or any redness or swelling.

If you need surgery or medical tests, tell the surgeon or doctor ahead of time if you have taken this medicine within the past few days. Store at room temperature away from moisture and heat. Do not allow liquid medicine to freeze.

What happens if I miss a dose?

Since this medicine is taken when 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 can be fatal.

The first signs of an acetaminophen overdose include loss of appetite, nausea, vomiting, stomach pain, sweating, and confusion or weakness. Later symptoms may include pain in your upper stomach, dark urine, and yellowing of your skin or the whites of your eyes.

Overdose symptoms may also include severe forms of some of the side effects listed in this medication guide.

What should I avoid while taking this medicine?

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 which can lead to a fatal overdose. Check the label to see if a medicine contains acetaminophen or APAP. Avoid drinking alcohol. It may increase your risk of liver damage while you are taking acetaminophen, and can increase certain side effects of doxylamine. This medicine may cause blurred vision or impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert and able to see clearly.

This medicine side effects

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

chest pain, rapid pulse;

fast, slow, or uneven heart rate;

severe dizziness or anxiety, feeling like you might pass out;

severe headache;

mood changes, confusion, hallucinations, severe nervousness;

tremor, seizure (convulsions);

fever, easy bruising or bleeding, unusual weakness;

urinating less than usual or not at all;

nausea, pain in your upper stomach, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of your skin or eyes); or

dangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, anxiety, chest pain, uneven heartbeats, seizure).

Less serious side effects may include:

dizziness, drowsiness, mild headache;

dry mouth, nose, or throat;

constipation, diarrhea, mild nausea, upset stomach;

blurred vision;

feeling restless or irritable; or

sleep problems (insomnia).

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 this medicine?

Ask a doctor or pharmacist before using this medicine if you regularly use other medicines that make you sleepy (such as narcotic pain medication, sedatives, sleeping pills, muscle relaxers, and medicine for seizures, depression or anxiety). They can add to sleepiness caused by doxylamine.

Ask a doctor or pharmacist if it is safe for you to use acetaminophen, doxylamine, and dextromethorphan if you are also using any of the following drugs:

leflunomide (Arava);

topiramate (Topamax);

zonisamide (Zonegran);

an antibiotic, antifungal medicine, sulfa drug, or tuberculosis medicine;

an antidepressant;

birth control pills or hormone replacement therapy;

bladder or urinary medications;

blood pressure medication;

a bronchodilator;

cancer medicine;

cholesterol-lowering medications such as Lipitor, Niaspan, Zocor, Vytorin, and others;

gout or arthritis medications (including gold injections);

HIV/AIDS medication;

medication for nausea and vomiting, stomach ulcers, or irritable bowel syndrome;

medicines to treat psychiatric disorders;

an NSAID such as Advil, Aleve, Arthrotec, Cataflam, Celebrex, Indocin, Motrin, Naprosyn, Treximet, Voltaren, others; or

seizure medication.

This list is not complete and there may be other drugs that can affect acetaminophen, dextromethorphan, and doxylamine. 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 Nyquil Cold & Flu resources

Nyquil Cold & Flu Use in Pregnancy & Breastfeeding
Nyquil Cold & Flu Drug Interactions
Nyquil Cold & Flu Support Group
0 Reviews for Nyquil Cold & Flu - Add your own review/rating

Compare Nyquil Cold & Flu with other medications

Cough
Pain

Where can I get more information?

Your pharmacist can provide more information about acetaminophen, dextromethorphan, and doxylamine.

insulin zinc

Generic Name: insulin zinc (IN suh lin ZINK)

Brand names: Humulin L, Iletin Lente, Insulin Lente Pork, Novolin L, HumuLIN L, NovoLIN L, Iletin II Lente Pork

What is insulin zinc?

Insulin is a hormone naturally produced by the pancreas. Insulin enables the body to use the sugar in food as a source of energy. When the body does not produce enough insulin, or when the insulin produced by the body is not effective enough, the condition is called diabetes mellitus. This condition allows sugar levels in the blood to become very high. Diabetics must use man-made insulin or insulin that comes from pigs (which is very similar to human insulin) to lower these high blood sugar levels.

Insulin zinc is used is used in the treatment of diabetes mellitus.

Insulin zinc may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about insulin zinc?

Know the signs and symptoms of low blood sugar (hypoglycemia), which include shaking; nausea; headache; drowsiness; weakness; dizziness; fast heartbeat; sweating; pale, cool skin; anxiety; and difficulty concentrating. Carry a piece of candy or glucose tablets with you to treat episodes of low blood sugar.

Follow any diet and exercise plan that you have developed with your doctor or nurse. Changes in what you eat or how much you exercise can change the amount of insulin that you need to control your blood sugar levels.

Ask your doctor or nurse what to do if you are sick with a cold, flu, or fever. These illnesses may change your insulin requirements.

Do not change the brand of insulin zinc or syringe that you are using without first talking to your doctor or pharmacist. Some brands of insulin 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 insulin zinc?

Do not use insulin zinc if you are allergic to insulin or if you have intolerance to a certain insulin zinc product.

Before using insulin, tell your doctor if you have any other medical conditions or if you take other prescription or over-the-counter medications, including vitamins, minerals, and herbal supplements.

Before using insulin zinc, tell your doctor if you have kidney or liver disease. You may require a dosage adjustment or special monitoring during treatment.

Most insulins can be used during pregnancy and breast-feeding. They are not expected to be harmful to an unborn baby. It is very important to control blood sugar levels during pregnancy and breast-feeding and insulin is often chosen as the treatment. Some types of insulin may be better than others for use during pregnancy and breast-feeding. Talk to your doctor about the use of insulin during pregnancy and breast-feeding.

How should I use insulin zinc?

Use insulin zinc exactly as directed by your doctor. If you do not understand these instructions, ask your doctor, nurse, or pharmacist to explain them to you.

If insulin zinc has been stored in the refrigerator, it can be warmed to room temperature before use. Also, roll it slightly between your hands to be sure that it is mixed. Never shake an insulin zinc suspension vigorously.

If you are mixing different types of insulins in the same syringe, follow your doctor's directions and always draw up the different insulins in the same order (usually the clear insulin first). This may help prevent a dosage error. Do not mix different insulins in the same syringe unless specifically directed to do so by your doctor. Some types of insulins should not be mixed.

Do not use any insulin that is discolored, looks thick, has particles in it, or looks different from previous bottles, cartridges, or pens of insulin zinc.

Change injection sites as directed by your doctor. Usually, you should not inject within 1 inch of the same site within 1 month.

Never reuse a needle or syringe. Dispose of all needles and syringes in an appropriate, puncture-resistant disposal container.

Do not change the insulin strength (e.g., U-100) or insulin type (e.g., zinc, regular, lispro, etc.) unless your doctor recommends a change for you.

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

Ask your doctor or nurse what to do if you are sick with a cold, flu, or fever. These illnesses may change your insulin requirements.

Your healthcare provider may recommend regular monitoring of blood sugar levels with blood or urine tests.

Wear some type of medical identification bracelet, necklace, or other alert tag to inform others that you have diabetes and that you require insulin in the case of an emergency.

Proper foot care, eye care, dental care, and overall proper health care are important for people with diabetes. Visit your doctor, dentist, eye doctor, and other heath care practitioners as recommended by your doctor.

Store unopened vials of insulin zinc the refrigerator between 36 and 46 degrees Fahrenheit (2 and 8 degrees Celsius), in the original carton. Do not store insulin zinc in the freezer and do not allow it to freeze. Do not use insulin zinc if it has been frozen. Throw away any expired insulin zinc. Vials of insulin zinc can be kept unrefrigerated for up to 28 days, but should not be exposed to excessive heat or sunlight.

Once punctured, the insulin vial in use, whether stored in the refrigerator or at room temperature, must be used within 28 days. Throw away any unused insulin 28 days after the vial is first punctured.

What happens if I miss a dose?

Follow your doctor's directions if you miss a dose of insulin. To prevent missed doses, be sure to always have enough insulin on hand, especially if you are going on vacation.

What happens if I overdose?

Seek emergency medical attention if an overdose is suspected.

Symptoms of an insulin overdose reflect very low blood sugar levels and include headache, irregular heartbeat, increased heart rate or pulse, sweating, tremor, nausea, increased hunger, and anxiety.

What should I avoid while using insulin zinc?

Do not use alcohol without first talking to your doctor. It lowers blood sugar, and you may experience dangerously low blood sugar levels.

Follow any diet and exercise plan that you have developed with your doctor or nurse. Changes in what you eat or how much you exercise can change the amount of insulin you need to control your blood sugar levels.

Insulin zinc side effects

Rarely, people have allergic reactions to insulin. Seek emergency medical attention if you experience an allergic reaction (difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives).

The side effects of insulin therapy result mostly from blood sugar levels that are either too high or too low. You should be familiar with the symptoms of both high and low blood sugar levels and know how to treat both conditions. Also, be sure your family and close friends know how to help you in an emergency.

Low blood sugar may occur when too much insulin is used; when meals are missed or delayed; if you exercise more than usual; during illness, especially with vomiting or diarrhea; if you take other medications; after drinking alcohol; and in other situations.

Hypoglycemia, or low blood sugar, has the following symptoms: shaking; nausea; headache; drowsiness; weakness; dizziness; fast heartbeat; sweating; pale, cool skin; anxiety; and difficulty concentrating.

Keep sugary candy, fruit juice, or glucose tablets on hand to treat episodes of low blood sugar.

Increased blood sugar may occur if not enough insulin is used, if you eat significantly more food then usual, if you exercise less than usual, if you take other medications, if you have a fever or other illness, and in other situations.

Hyperglycemia, or high blood sugar, has the following symptoms: increased thirst, increased hunger, and increased urination.

Monitor your blood sugar levels and ask your doctor how to adjust your insulin doses if your blood sugar levels are too high.

Side effects may also occur at the site of injection. If the area becomes thickened, hard, or pitted, talk to your doctor before injecting at that site again.

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome.

Insulin zinc Dosing Information

Usual Adult Dose for Gestational Diabetes:

Insulin zinc is an intermediate acting insulin which is injected subcutaneously 1 to 3 times daily. It may provide 30 to 50% of the daily basal insulin requirements.

Insulin dosage should be individualized to achieve/maintain a target blood glucose level and is determined by various factors including body weight, body fat, physical activity, insulin sensitivity, blood glucose levels, and target blood glucose.

Conventional regimen: The total daily insulin dose is administered as a mixture of rapid/short-acting and intermediate-acting insulins in 1 to 2 injections. Twice daily injections are preferred for better glycemic control. With the 2-injection regimen, generally two-thirds of the daily dose is given before breakfast and one-third is given before the evening meal.

Intensive regimen: The total daily dose is administered as 3 or more injections or by continuous subcutaneous infusion to cover basal and pre-meal bolus insulin requirements. The basal requirement is approximately 30 to 50% of the total dose, given as intermediate or long-acting insulin (NPH, zinc, extended zinc, lispro-protamine, glargine), 1 to 2 times daily. Meal boluses are approximately 50 to 70% of the total dose, given as rapid/short-acting insulin (regular, aspart, lispro) 2 to 5 times daily before meals. Common regimens include injections of rapid/short acting insulin before each meal along with injections of intermediate or long-acting insulin in the morning and/or evening. Dosage adjustments are made to achieve target blood glucose levels and are based on frequent blood glucose measurements, diet and exercise levels.

Total daily insulin requirements:
Initial dose: 0.5 to 0.8 unit/kg/day subcutaneously
Honeymoon phase: 0.2 to 0.5 unit/kg/day subcutaneously
Split dose therapy: 0.5 to 1.2 unit/kg/day subcutaneously
Insulin resistance: 0.7 to 2.5 units/kg/day subcutaneously

Usual Adult Dose for Diabetes Mellitus Type I:

Usual Adult Dose for Diabetes Mellitus Type II:

Insulin zinc is an intermediate acting insulin which is injected subcutaneously 1 to 3 times daily.

Diet and lifestyle modifications are recommended as initial treatment for type II diabetes, followed by oral agents. Insulin may be considered if patients are very hyperglycemic or symptomatic and/or not controlled with oral agents. Insulin may exacerbate obesity, further increase insulin resistance, and increase the frequency of hypoglycemia.

Insulin dosage should be individualized to achieve/maintain a target blood glucose level and is determined by various factors including body weight, body fat, physical activity, insulin sensitivity, blood glucose levels, and target blood glucose.

Conventional regimen:
Initial dose, adjunct: When used as an adjunct to oral hypoglycemic agents, isophane (NPH) or zinc insulin 0.1 unit/kg at bedtime has been used.

Initial dose, monotherapy: Total daily requirement: 0.1 unit/kg/day subcutaneously. When insulin is used alone, twice daily injections are recommended for better glycemic control. The total daily insulin dose is administered as a mixture of rapid/short-acting and intermediate-acting insulins in 1 to 2 injections. With the 2-injection regimen, generally two-thirds of the daily dose is given before breakfast and one-third is given before the evening meal. Once daily injections are sometimes used in children with suboptimal compliance; however, this may lead to more nocturia, fasting hyperglycemia, morning glucosuria, and a risk of ketoacidosis if the doses are missed.
Maintenance dose, monotherapy: Total daily insulin requirements may progress to 1.5 to 2.5 units/kg or higher in patients with obesity and insulin resistance.

Intensive regimen:
The necessity for and efficacy of intensive insulin therapy in type II diabetes has been controversial. The total daily dose is administered as 3 or more injections or by continuous subcutaneous infusion to cover basal and pre-meal bolus insulin requirements. This method may be appropriate for closely supervised and highly motivated older children or adolescents who are able to inject their insulin, monitor their blood glucose, and recognize hypoglycemia. The basal requirement is approximately 30 to 50% of the total dose, given as intermediate or long-acting insulin (NPH, zinc, extended zinc, lispro-protamine, glargine), 1 to 2 times daily. Meal boluses are approximately 50 to 70% of the total dose, given as rapid/short-acting insulin (regular, aspart, lispro) 2 to 5 times daily before meals. Common regimens include injections of rapid/short acting insulin before each meal along with injections of intermediate or long-acting insulin in the morning and/or evening. Dosage adjustments are made to achieve target blood glucose levels and are based on frequent blood glucose measurements, diet and exercise levels.
Initial dose, monotherapy: 0.5 to 1.5 unit/kg/day subcutaneously.
Maintenance dose, monotherapy: Total daily insulin requirements may progress to 2.5 units/kg or higher in patients with obesity and insulin resistance.

Usual Pediatric Dose for Diabetes Mellitus Type I:

Insulin zinc is an intermediate acting insulin which is injected subcutaneously 1 to 3 times daily. It may provide 30 to 50% of the daily basal insulin requirements.

Insulin dosage should be individualized to achieve/maintain a target blood glucose level and is determined by various factors including body weight, body fat, physical activity, insulin sensitivity, blood glucose levels, and target blood glucose.

Conventional regimen: The total daily insulin dose is administered as a mixture of rapid/short-acting and intermediate-acting insulins in 1 to 2 injections. Twice daily injections are recommended for better glycemic control. With the 2-injection regimen, generally two-thirds of the daily dose is given before breakfast and one-third is given before the evening meal. Once daily injections are sometimes used in children with suboptimal compliance; however, this may lead to more nocturia, fasting hyperglycemia, morning glucosuria, and a risk of ketoacidosis if the doses are missed.

Intensive regimen: The total daily dose is administered as 3 or more injections or by continuous subcutaneous infusion to cover basal and pre-meal bolus insulin requirements. This method may be appropriate for closely supervised and highly motivated older children or adolescents who are able to inject their insulin, monitor their blood glucose, and recognize hypoglycemia. The basal requirement is approximately 30 to 50% of the total dose, given as intermediate or long-acting insulin (NPH, zinc, extended zinc, glargine), 1 to 2 times daily. Meal boluses are approximately 50 to 70% of the total dose, given as rapid/short-acting insulin (regular, lispro) 2 to 5 times daily before meals. Common regimens include injections of rapid/short acting insulin before each meal along with injections of intermediate or long-acting insulin in the morning and/or evening. Dosage adjustments are made to achieve target blood glucose levels and are based on frequent blood glucose measurements, diet and exercise levels.

Total daily insulin requirements:
Initial dose: 0.5 to 0.8 unit/kg/day subcutaneously
Honeymoon phase: 0.2 to 0.5 unit/kg/day subcutaneously
Split dose therapy: 0.5 to 1.2 unit/kg/day subcutaneously
Adolescents during growth spurts. 0.8 to 1.5 units/kg/day subcutaneously

Usual Pediatric Dose for Diabetes Mellitus Type II:

Insulin zinc is an intermediate acting insulin which is injected subcutaneously 1 to 3 times daily.

Diet and lifestyle modifications are recommended as initial treatment for type II diabetes, followed by oral agents (metformin). Insulin may be considered if children are very hyperglycemic or symptomatic and/or not controlled with oral agents. Insulin may exacerbate obesity, further increase insulin resistance, and increase the frequency of hypoglycemia.

Insulin dosage should be individualized to achieve/maintain a target blood glucose level and is determined by various factors including body weight, body fat, physical activity, insulin sensitivity, blood glucose levels, and target blood glucose.

Conventional regimen:
Initial dose, adjunct: When used as an adjunct to metformin, isophane (NPH) or zinc insulin 0.1 unit/kg at bedtime has been used.

Initial dose, monotherapy: Total daily requirement: 0.1 unit/kg/day subcutaneously. When insulin is used alone, twice daily injections are recommended for better glycemic control. The total daily insulin dose is administered as a mixture of rapid/short-acting and intermediate-acting insulins in 1 to 2 injections. With the 2-injection regimen, generally two-thirds of the daily dose is given before breakfast and one-third is given before the evening meal. Once daily injections are sometimes used in children with suboptimal compliance; however, this may lead to more nocturia, fasting hyperglycemia, morning glucosuria, and a risk of ketoacidosis if the doses are missed.
Maintenance dose, monotherapy: Total daily insulin requirements may progress to 1.5 to 2.5 units/kg or higher in patients with obesity and insulin resistance.

Intensive regimen:
The necessity for and efficacy of intensive insulin therapy in type II diabetes has been controversial. The total daily dose is administered as 3 or more injections or by continuous subcutaneous infusion to cover basal and pre-meal bolus insulin requirements. This method may be appropriate for closely supervised and highly motivated older children or adolescents who are able to inject their insulin, monitor their blood glucose, and recognize hypoglycemia. The basal requirement is approximately 30 to 50% of the total dose, given as intermediate or long-acting insulin (NPH, zinc, extended zinc, glargine), 1 to 2 times daily. Meal boluses are approximately 50 to 70% of the total dose, given as rapid/short-acting insulin (regular, lispro) 2 to 5 times daily before meals. Common regimens include injections of rapid/short acting insulin before each meal along with injections of intermediate or long-acting insulin in the morning and/or evening. Dosage adjustments are made to achieve target blood glucose levels and are based on frequent blood glucose measurements, diet and exercise levels.
Initial dose, monotherapy: 0.5 to 1.5 unit/kg/day subcutaneously.
Maintenance dose, monotherapy: Total daily insulin requirements may progress to 2.5 units/kg or higher in patients with obesity and insulin resistance.

What other drugs will affect insulin zinc?

Many drugs can interact with insulin or affect blood sugar levels. Do not take any other prescription or over-the-counter medicines, including vitamins, minerals, and herbal products, without first talking to your doctor or pharmacist during treatment with insulin.

More insulin zinc resources

Insulin zinc Use in Pregnancy & Breastfeeding
Insulin zinc Drug Interactions
Insulin zinc Support Group
1 Review for Insulin zinc - Add your own review/rating

Humulin L Prescribing Information (FDA)

Compare insulin zinc with other medications

Diabetes, Type 1
Diabetes, Type 2
Gestational Diabetes

Where can I get more information?

Your pharmacist has additional information about insulin zinc written for health professionals that you may read.

What does my medication look like?

Insulin zinc is available under the brand names Humulin L, Novolin L, Iletin II Lente, and Insulin Lente Pork. The insulin should be a clear, colorless or evenly colored liquid after it is gently rolled or shaken. Do not use it if it appears to be thick, looks sticky, has particles in it, or looks different from previous bottles of insulin that you have had. Always use the same brand unless your doctor approves a change. Ask your pharmacist, nurse, or doctor any questions you have about this medication.

Humulin L-10 mL vials

Novolin L-10 mL vials

Iletin II Lente-10 mL vials

Insulin Lente Pork-10 mL vials

Wednesday 28 March 2012

Spiriva Handihaler

Generic Name: Tiotropium Bromide
Class: Antimuscarinics/Antispasmodics
VA Class: RE105
Chemical Name: di-2-thienylglycolate-6β,7β-Epoxy-3β-hydroxy-8-methyl-1αH,5αH-tropanium bromide
Molecular Formula: C₁₉H₂₂BrNO₄S₂
CAS Number: 139404-48-1

Introduction

Bronchodilator; a synthetic quaternary ammonium antimuscarinic agent.¹

Uses for Spiriva Handihaler

COPD

Long-term treatment of reversible bronchospasm associated with COPD, including chronic bronchitis and emphysema.¹ ¹² ¹³ ¹⁴ ¹⁵

A long-acting bronchodilator (e.g., orally inhaled salmeterol, formoterol, tiotropium) or an inhaled corticosteroid recommended for maintenance monotherapy in patients with moderate to severe COPD (e.g., FEV₁ 30 to <80% of predicted¹⁵ or, alternatively, <60% of predicted)¹⁸ who have persistent symptoms not relieved by as-needed therapy with a selective, short-acting inhaled β₂-adrenergic agonist.¹⁵ ¹⁸ Maintenance therapy with long-acting bronchodilators in such patients more effective and more convenient than regular therapy with short-acting bronchodilators.¹³ ¹⁵ ¹⁸ Insufficient data to favor one maintenance monotherapy over another in patients with moderate to severe COPD.¹⁵ ¹⁸ In selected patients with inadequate response, may use a combination of several long-acting bronchodilators, such as tiotropium, and a long-acting β₂-adrenergic agonist.¹³ ¹⁵

In patients with severe to very severe COPD (e.g., FEV₁ <30 to <50% of predicted), some clinicians recommend addition of an inhaled corticosteroid to one or more long-acting bronchodilators, given separately or in fixed combination;¹² ¹⁴ ¹⁵ however, benefits of combination therapy over monotherapy not consistently established.¹⁵ ¹⁸ If inadequate response or limiting adverse effects occur, may consider the addition or substitution of extended-release oral theophylline.¹² ¹⁴ ¹⁵

Not indicated for the initial treatment of acute episodes of bronchospasm or acute exacerbations of COPD;¹ ⁵ a drug with a more rapid onset of action (e.g., a short-acting β-adrenergic agonist) preferred.² ³ ⁷ ⁸

Spiriva Handihaler Dosage and Administration

Administration

Administer by oral inhalation only using a special oral inhalation device (HandiHaler) that delivers powdered drug from capsules.¹ ⁵

Do not take capsules orally, as intended effects on the lungs will not be obtained.¹ ⁵ ¹⁶

Oral Inhalation

Open the dust cap by pressing the green piercing button.⁵ Pull the dust cap upward on the side opposite the hinge of the Handihaler device to expose the mouthpiece.⁵ Open the mouthpiece by pulling the mouthpiece ridge upward on the side opposite the hinge of the inhaler to expose the center chamber.⁵ Carefully open the blister card to expose only one capsule immediately before use.¹ ⁵ Place capsule into the center chamber of the inhaler,¹ ⁵ and close the inhaler mouthpiece firmly until it snaps (clicks) into position, leaving the dust cap open (up).⁵ (See Stability.) Push down on the mouthpiece ridge to make sure that the mouthpiece is seated in the gray base of the inhaler.⁵ Hold the inhaler with the seated mouthpiece upward, depress the green button on the side of the inhaler completely (until the button is flush with the gray base of the inhaler), then release the button.¹ ⁵ The green button pierces the capsule and disperses the powdered drug upon inspiration.¹ ⁵ ¹¹ Do not press the green piercing button more than once.⁵ ¹¹

Exhale completely; do not exhale into the HandiHaler device.⁵ Hold the inhaler by the gray base; take care not to block the air intake vents near the mouthpiece ridge.⁵ With the head kept level, place the mouthpiece of the inhaler between the lips (inhaler is in a horizontal position) and inhale deeply and slowly through the inhaler with a rate sufficient to hear or feel the loaded capsule vibrate.⁵ ¹¹ Pressure from inhalation will disperse the drug from center chamber into air stream created by the patient’s inhalation.¹ ⁵ Continue breathing until the lungs are full.⁵ Remove the inhaler from the mouth and hold the breath for as long as comfortable, then resume normal breathing.⁵ Breathe out completely and inhale once again to ensure full delivery of the powder.⁵ Do not press the green piercing button again.⁵ Upon completion of the second inhalation, open the mouthpiece and tip the device to dispose of the used capsule; close the mouthpiece and dust cap of the inhaler device.⁵

Do not take extra doses despite not being able to hear or feel the capsule vibrate.⁵ Tap the inhaler device on a table, holding the gray base in an upright position.⁵ Then check to see that the mouthpiece is properly seated in the gray base and attempt to inhale through the device again.⁵ (See Advice to Patients.)

If no improvement in COPD symptoms, make sure patient is inhaling the drug using the oral inhaler rather than swallowing the dry-powder capsules.¹⁶ (See Accidental Oral Ingestion under Cautions.)

Clean the Handihaler device once a month.⁵ Open the dust cap and mouthpiece, then open the base by lifting the green piercing button; rinse with warm water (do not use cleaning agents or detergents) to remove any remaining powder.⁵ Dry the inhaler thoroughly; leave dust cap, mouthpiece, and gray base open to air dry for 24 hours.⁵ Do not use the inhaler when wet.⁵ If needed, clean the outside of the mouthpiece with a moist, but not wet, tissue.⁵ ¹¹

Dosage

Available as tiotropium bromide monohydrate; dosage expressed in terms of anhydrous tiotropium.¹ ¹¹

Each capsule contains 18 mcg of tiotropium as an inhalation powder.¹ However, the precise amount of drug delivered to the lungs depends on factors such as the patient’s inspiratory flow.¹

Adults

COPD

Inhalation

18 mcg (contents of one capsule) once daily.¹ ¹¹

Special Populations

Hepatic Impairment

No dosage adjustments required.¹

Renal Impairment

No dosage adjustments required.¹

Geriatric Patients

No dosage adjustments required.¹

Cautions for Spiriva Handihaler

Contraindications

Known hypersensitivity to tiotropium bromide or any ingredient in the formulation.¹

Known hypersensitivity to atropine or its derivatives (e.g., ipratropium).¹

Warnings/Precautions

Warnings

Acute Bronchospasm

Delayed onset of action; not indicated for initial treatment.¹ ⁵ Do not use for the treatment of acute episodes of bronchospasm (i.e., as rescue therapy).¹ ⁵

Possible Increased Risk of Stroke, Mortality, and/or Cardiovascular Events

Data are conflicting; possible increased risk of stroke identified from ongoing safety monitoring and pooled analysis of placebo-controlled trials.¹⁹ Data on approximately 13,500 patients with COPD suggest an absolute excess risk of 2 strokes per 1000 patient-years with exposure to tiotropium compared with that of placebo.¹⁹ Other observational data involving over 32,000 patients and pooled analyses of almost 15,000 patients suggest an increased risk of mortality and/or cardiovascular events with use of inhaled anticholinergic agents, including tiotropium bromide.²⁰ ²¹ However, increased risk of stroke with tiotropium not revealed in a preliminary analysis of a placebo-controlled trial (Understanding the Potential Long-term Impacts on Function with Tiotropium [UPLIFT]) in approximately 6000 patients with COPD.¹⁹ Results of these analyses pending confirmation by FDA; postmarketing adverse event reports and results of the UPLIFT trial currently under review.¹⁹

Sensitivity Reactions

Hypersensitivity Reactions

Immediate hypersensitivity reactions, including angioedema, reported.⁵ Possible acute paradoxical bronchospasm.¹ ¹¹ If such reactions occur, discontinue immediately and consider alternative therapy.¹

General Precautions

Ocular Effects

Possible temporary blurred vision, worsening of acute angle-closure glaucoma (e.g., ocular pain or discomfort, blurred vision, visual halos, or colored images in association with conjunctival congestion and corneal edema), or pupillary dilation following inadvertent contact of tiotropium with the eyes.¹ ⁵ ⁸ ¹¹ Miotic eye drops alone are not considered effective treatment for this condition.¹ (See Advice to Patients.)

GU Effects

Possible urinary retention, urinary difficulty,¹ or urinary tract infection.¹

May worsen symptoms and signs associated with prostatic hyperplasia or bladder neck obstruction.¹ ¹¹ Use with caution in patients with these conditions.¹

Accidental Oral Ingestion

Acute intoxication unlikely following inadvertent oral ingestion of the dry-powder capsules for oral inhalation since the drug is not well absorbed systemically.¹ Adverse effect reports uncommon following ingestion of dry-powder capsules.¹⁶

Specific Populations

Pregnancy

Category C.¹

Lactation

Distributed into milk in rodents; not known whether tiotropium is distributed into human milk.¹ Use caution.¹

Pediatric Use

Safety and efficacy not established in children <18 years of age.¹ ¹¹

Geriatric Use

Possible increased incidence of dry mouth, constipation, and urinary tract infection compared with younger adults.¹ However, no overall differences in efficacy relative to younger adults.¹

Hepatic Impairment

Pharmacokinetics not evaluated, but impact of hepatic impairment should be minimal.¹

Renal Impairment

Clearance may be decreased; closely monitor patients with moderate to severe renal impairment (CL_cr of ≤50 mL/minute) during therapy.¹

Common Adverse Effects

Upper respiratory tract infection,¹ dry mouth,¹ accidents,¹ sinusitis,¹ pharyngitis,¹ urinary tract infection,¹ chest pain (nonspecific),¹ rhinitis,¹ dyspepsia,¹ abdominal pain,¹ edema (dependent),¹ constipation,¹ vomiting,¹ infection,¹ moniliasis,¹ epistaxis,¹ myalgia,¹ rash.¹

Interactions for Spiriva Handihaler

Metabolized by CYP isoenzymes, principally CYP2D6 and CYP3A4.¹ ⁸

Does not inhibit CYP1A1, 1A2, 2B6, C29, 2C19, 2D6, 2E1, or 3A4.¹

Specific Drugs

Drug	Interaction	Comments
β₂-Adrenergic agonists	No adverse drug interactions reported¹
Antimuscarinic agents	Interaction not studied¹	Concomitant use not recommended by manufacturer¹
Corticosteroids, oral and inhaled	No adverse drug interactions reported¹
Histamine H₂-receptor antagonists	Increased AUC and decreased renal clearance of IV tiotropium (not currently available in the US) with concomitant cimetidine but not ranitidine¹	Pharmacokinetic interactions not considered clinically important¹
Methylxanthines	No adverse drug interactions reported¹

Spiriva Handihaler Pharmacokinetics

Absorption

Bioavailability

Following inhalation, absolute bioavailability is 19.5%.¹ Most of a dose is swallowed¹ ¹¹ and minimally absorbed into systemic circulation;¹ the fraction reaching the lungs appears to be readily absorbed.¹ ⁷ ¹¹ Peak plasma concentrations following oral inhalation are attained within 5 minutes.¹

Onset

Following oral inhalation, bronchodilation evident within 30 minutes.⁴

Duration

Bronchodilation generally persists for >24 hours.¹

Food

Food does not appear to affect absorption from GI tract.¹

Special Populations

In patients with renal impairment, increased plasma drug concentrations and AUC.¹

Distribution

Extent

Widely distributed into tissues.¹ Does not penetrate the blood-brain barrier in animals.¹

Plasma Protein Binding

72%.¹

Elimination

Metabolism

Metabolized to a limited extent, principally by isoenzymes CYP2D6 and 3A4.¹ ⁸

Elimination Route

Excreted principally in the feces (86%), mainly as unabsorbed drug, and in the urine (approximately 14%) as unchanged drug.¹ ⁷ ⁸

Half-life

Terminal elimination half-life is 5–6 days following oral inhalation.¹

Special Populations

In patients with renal impairment, reduced clearance.¹

Stability

Storage

Parenteral

Powder for Oral Inhalation

25°C (may be exposed to 15–30°C).¹ Do not expose to extreme temperatures and moisture.¹

Keep capsules in sealed blisters until immediately before use.¹ ⁵ Do not store used or unused capsules in the inhaler device.⁵ Remove only one capsule immediately before use or effectiveness of the drug may be reduced.¹ ⁵ Discard additional capsules if opened and exposed to air (i.e., not intended for immediate use).¹ ⁵ ¹¹

ActionsActions

Competitively and reversibly inhibits the actions of acetylcholine and other cholinergic stimuli at M₃ receptors in the smooth muscle of the respiratory tract, leading to bronchodilation.¹ ⁷ ¹¹ ¹⁵

Advice to Patients

Importance of providing patient a copy of manufacturer’s patient information.⁵

Importance of informing a clinician of allergies to any medications prior to initiation of tiotropium bromide therapy.⁵

Importance of adequate understanding of proper storage, preparation, and inhalation techniques, including use of the inhalation delivery system (HandiHaler).¹ ⁵ ¹⁶

Importance of not using the HandiHaler device to administer other drugs.⁵ ¹¹

Importance of consulting a clinician of faulty inhaler performance (i.e., if capsule vibration is not felt or heard upon inhalation) when certain procedures (i.e., confirming that the mouthpiece is firmly seated in the gray base, tapping the inhaler gently on a table) do not improve inhaler performance.⁵

Importance of avoiding inadvertent contact of the drug with the eyes, as contact may cause blurred vision and pupillary dilation.¹ ⁵

Importance of not using tiotropium to relieve acute symptoms or exacerbations of COPD.¹ ⁵

Importance of patients consulting clinician before discontinuing tiotropium therapy if they are concerned about potential adverse effects (e.g., stroke).¹⁹

Importance of informing a clinician if eye pain or discomfort, blurred vision, or visual halos or colored images in association with conjunctival congestion or corneal edema occur.¹

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (e.g., eye drops) and herbal supplements, as well as any concomitant illnesses (e.g., urinary difficulty, enlarged prostate, angle-closure glaucoma).¹ ⁵ ¹¹

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹ ⁵

Importance of informing patients of other important precautionary information.¹ (See Cautions.)

Preparations

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

Tiotropium Bromide
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral Inhalation	Powder for Inhalation (contained in capsules)	18 mcg (of anhydrous tiotropium)	Spiriva HandiHaler	Boehringer Ingelheim (comarketed by Pfizer)

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Spiriva HandiHaler 18MCG Capsules (BOEHRINGER INGELHEIM): 30/$230 or 90/$670

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions August 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Boehringer Ingelheim. Spiriva HandiHaler (tiotropium bromide) inhalation powder prescribing information. Ridgefield, CT; 2007 Dec.

2. Veterans’ Health Administration Department of Veteran Affairs. The pharmacologic management of chronic obstructive pulmonary disease. Washington, DC: Veterans’ Health Administration; 1999 June. Pharmacy Benefits Management No. 99-0012. Available at . Accessed Sep. 30, 2002.

3. Veterans’ Health Administration, Department of Veterans’ Affairs. VHA/DOD clinical practice guideline for the management of chronic obstructive pulmonary disease: complete summary. Washington, DC: Veterans’ Health Administration; 1999 Aug.

4. Vincken W, van Noord JA, Greefhorst AP et al. Improved health outcomes in patients with COPD during 1 yr’s treatment with tiotropium. Eur Respir J. 2002; 19:209-16. [PubMed 11871363]

5. Boehringer Ingelheim. Spiriva HandiHaler (tiotropium bromide) inhalation powder patient instructions for use. Ridgefield, CT; 2007 Dec.

6. Casaburi R, Mahler DA, Jones PW et al. A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease. Eur Respir J. 2002; 19:217-24. [IDIS 514612] [PubMed 11866001]

7. Hvizdos KM, Goa KL. Tiotropium bromide. Drugs. 2002; 62:1195-203. [PubMed 12010082]

8. Anon. Tiotropium (Spiriva) for COPD. Med Lett Drugs Ther. 2004: 46:41-2.

9. Brusasco V, Hodder R, Miravitlles M et al. Health outcomes following treatment for six months with once daily tiotropium compared with twice daily salmeterol in patients with COPD. Thorax. 2003: 58:399-404.

10. Donohue JF, van Noord JA, Bateman ED et al. A 6-month, placebo-controlled study comparing lung function and health status changes in COPD patients treated with tiotropium or salmeterol. Chest. 2002: 122:47-55.

11. Boehringer Ingelheim, Ridgefield, CT: Personal communication.

12. ATS/ERS Standards for the diagnosis and management of patients with COPD. New York, NY: American Thoracic Society, European Respiratory Society; 2004. Available at . Accessed Dec. 8, 2004.

13. O’Donnell DE, Aaron S, Bourbeau J et al. Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease-2003. Can Respir J. 2003; 10 (Suppl. A):11A-65A.

14. Celli BR, Macnee W. Standard for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J. 2004; 23:932-46. [PubMed 15219010]

15. National Heart, Lung, and Blood Institute/World Health Organization. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Bethesda, MD: National Heart, Lung, and Blood Institute, Global Initiative for Chronic Obstructive Lung Disease, World Health Organization; 2007 Dec. Available at: . Accessed 2008 May 19.

16. Food and Drug Administration. FDA public health advisory: Important information on correct use of Spiriva and Foradil capsules. Rockville, MD; 2008 Feb 29. Available at . Accessed 2008 Apr 23.

18. Qaseem A, Snow V, Shekelle P et al. Diagnosis and management of stable chronic obstructive pulmonary disease: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2007; 147:633-8. [PubMed 17975186]

19. Food and Drug Administration. Early communication about an ongoing safety review of tiotropium (marketed as Spiriva Handihaler). Rockville, MD; 2008 Oct 7. Available at . Accessed 2008 Oct 8.

20. Singh S, Loke YK, Furberg CD. Inhaled anticholinergics and risk of major adverse cardiovascular events in patients with chronic obstructive pulmonary disease. JAMA. 2008; 300:1439-50. [PubMed 18812535]

21. Lee TA, Pickard AS, Au DH et al. Risk of death associated with medications for recently diagnosed chronic obstructive pulmonary disease. Ann Intern Med. 2008; 149:380-90. [PubMed 18794557]

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COPD, Maintenance

Monday 26 March 2012

Lamotrigine 50mg Tablets

1. Name Of The Medicinal Product

LAMOTRIGINE 50mg TABLETS

2. Qualitative And Quantitative Composition

Each tablet contains 50mg Lamotrigine.

For excipients, see 6.1

3. Pharmaceutical Form

Tablet.

Light yellow, round, flat, uncoated tablets with a score line on one side.

4. Clinical Particulars

4.1 Therapeutic Indications

Epilepsy

Adults and adolescents aged 13 years and above

− Adjunctive or monotherapy treatment of partial seizures and generalised seizures, including tonic-clonic seizures.

− Seizures associated with Lennox-Gastaut syndrome. Lamotrigine Tablets is given as adjunctive therapy but may be the initial antiepileptic drug (AED) to start with in Lennox-Gastaut syndrome.

Children and adolescents aged 2 to 12 years

− Adjunctive treatment of partial seizures and generalised seizures, including tonic-clonic seizures and the seizures associated with Lennox-Gastaut syndrome.

− Monotherapy of typical absence seizures.

Bipolar disorder

Adults aged 18 years and above

− Prevention of depressive episodes in patients with bipolar I disorder who experience predominantly depressive episodes (see section 5.1).

Lamotrigine Tablets is not indicated for the acute treatment of manic or depressive episodes.

4.2 Posology And Method Of Administration

Method of Administration

Lamotrigine Tablets should be swallowed whole with a little water and should not be chewed or crushed.

Posology

Restarting therapy

Prescribers should assess the need for escalation to maintenance dose when restarting Lamotrigine Tablets in patients who have discontinued Lamotrigine Tablets for any reason, since the risk of serious rash is associated with high initial doses and exceeding the recommended dose escalation for lamotrigine (see section 4.4). The greater the interval of time since the previous dose, the more consideration should be given to escalation to the maintenance dose. When the interval since discontinuing lamotrigine exceeds five half-lives (see section 5.2), Lamotrigine Tablets should generally be escalated to the maintenance dose according to the appropriate schedule.

It is recommended that Lamotrigine Tablets not be restarted in patients who have discontinued due to rash associated with prior treatment with lamotrigine unless the potential benefit clearly outweighs the risk.

Epilepsy

The recommended dose escalation and maintenance doses for adults and adolescents aged 13 years and above (Table 1) and for children and adolescents aged 2 to 12 years (Table 2) are given below. Because of a risk of rash the initial dose and subsequent dose escalation should not be exceeded (see section 4.4).

When concomitant AEDs are withdrawn or other AEDs/medicinal products are added on to treatment regimes containing lamotrigine, consideration should be given to the effect this may have on lamotrigine pharmacokinetics (see section 4.5).

Table 1: Adults and adolescents aged 13 years and above - recommended treatment regimen in epilepsy

Treatment regimen	Weeks 1 + 2	Weeks 3 + 4	Usual maintenance dose
Monotherapy:	25mg/day (once a day)	50mg/day (once a day)	100 - 200mg/day (once a day or two divided doses) To achieve maintenance, doses may be increased by maximum of 50 - 100mg everyone to two weeks until optimal response is achieved 500mg/day has been required by some patients to achieve desired response
Adjunctive therapy WITH valproate (inhibitor of lamotrigine glucuronidation - see section 4.5):
This dosage regimen should be used with valproate regardless of any concomitant medicinal products	12.5mg/day (given as 25mg on alternate days)	25mg/day (once a day)	100 - 200mg/day (once a day or two divided doses) To achieve maintenance, doses may be increased by maximum of 25 - 50mg every one to two weeks until optimal response is achieved
Adjunctive therapy WITHOUT valproate and WITH inducers of lamotrigine glucuronidation (see section 4.5):
This dosage regimen should be used without valproate but with: phenytoin carbamazepine phenobarbital primidone rifampicin lopinavir/ritonavir	50mg/day (once a day)	100mg/day (two divided doses)	200 - 400mg/day (two divided doses) To achieve maintenance, doses may be increased by maximum of 100mg every one to two weeks until optimal response is achieved 700mg/day has been required by some patients to achieve desired response
Adjunctive therapy WITHOUT valproate and WITHOUT inducers of lamotrigine glucuronidation (see section 4.5):
This dosage regimen should be used with other medicinal products that do not significantly inhibit or induce lamotrigine glucuronidation	25mg/day (once a day)	50mg/day (once a day)	100 - 200mg/day (once a day or two divided doses) To achieve maintenance, doses may be increased by maximum of 50 - 100mg every one to two weeks until optimal response is achieved
In patients taking medicinal products where the pharmacokinetic interaction with lamotrigine is currently not known (see section 4.5), the treatment regimen as recommended for lamotrigine with concurrent valproate should be used.

Table 2: Children and adolescents aged 2 to 12 years - recommended treatment regimen in epilepsy (total daily dose in mg/kg body weight/day)

Treatment regimen	Weeks 1 + 2	Weeks 3 + 4	Usual maintenance dose
Monotherapy of typical absence seizures:	0.3mg/kg/day (once a day or two divided doses)	0.6mg/kg/day (once a day or two divided doses)	1 - 10mg/kg/day, although some patients have required higher doses (up to 15mg/kg/day) to achieve desired response (once a day or two divided doses) To achieve maintenance, doses may be increased by maximum of 0.6mg/kg/day every one to two weeks until optimal response is achieved
Adjunctive therapy WITH valproate (inhibitor of lamotrigine glucuronidation - see section 4.5):
This dosage regimen should be used with valproate regardless of any other concomitant medicinal products	0.15mg/kg/day * (once a day)	0.3mg/kg/day (once a day)	1 - 5mg/kg/day (once a day or two divided doses) To achieve maintenance, doses may be increased by maximum of 0.3mg/kg every one to two weeks until optimal response is achieved, with a maximum maintenance dose of 200mg/day
Adjunctive therapy WITHOUT valproate and WITH inducers of lamotrigine glucuronidation (see section 4.5):
This dosage regimen should be used without valproate but with: phenytoin carbamazepine phenobarbital primidone rifampicin lopinavir/ritonavir	0.6mg/kg/day (two divided doses)	1.2mg/kg/day (two divided doses)	5 - 15mg/kg/ day (once a day or two divided doses) To achieve maintenance, doses may be increased by maximum of 1.2mg/kg every one to two weeks until optimal response is achieved, with a maximum maintenance dose of 400mg/day
Adjunctive therapy WITHOUT valproate and WITHOUT inducers of lamotrigine glucuronidation (see section 4.5):
This dosage regimen should be used with other medicinal products that do not significantly inhibit or induce lamotrigine glucuronidation	0.3mg/kg/day (once a day or two divided doses)	0.6mg/kg/day (once a day or two divided doses)	1 - 10mg/kg/day (once a day or two divided doses) To achieve maintenance, doses may be increased by maximum of 0.6mg/kg every one to two weeks until optimal response is achieved, with a maximum of maintenance dose of 200mg/day
In patients taking medicinal products where the pharmacokinetic interaction with lamotrigine is currently not known (see section 4.5), the treatment regimen as recommended for lamotrigine with concurrent valproate should be used.

To ensure a therapeutic dose is maintained the weight of a child must be monitored and the dose reviewed as weight changes occur. It is likely that patients aged two to six years will require a maintenance dose at the higher end of the recommended range.

If epileptic control is achieved with adjunctive treatment, concomitant AEDs may be withdrawn and patients continued on Lamotrigine Tablets monotherapy.

Children below 2 years

There are limited data on the efficacy and safety of lamotrigine for adjunctive therapy of partial seizures in children aged 1 month to 2 years (see section 4.4). There are no data in children below 1 month of age. Thus Lamotrigine Tablets is not recommended for use in children below 2 years of age. If, based on clinical need, a decision to treat is nevertheless taken, see sections 4.4, 5.1 and 5.2.

Bipolar disorder

The recommended dose escalation and maintenance doses for adults of 18 years of age and above are given in the tables below. The transition regimen involves escalating the dose of lamotrigine to a maintenance stabilisation dose over six weeks (Table 3) after which other psychotropic medicinal products and/or AEDs can be withdrawn, if clinically indicated (Table 4). The dose adjustments following addition of other psychotropic medicinal products and/or AEDs are also provided below (Table 5). Because of the risk of rash the initial dose and subsequent dose escalation should not be exceeded (see section 4.4).

Table 3: Adults aged 18 years and above - recommended dose escalation to the maintenance total daily stabilisation dose in treatment of bipolar disorder

Treatment Regimen	Weeks 1 + 2	Weeks 3 + 4	Week 5	Target Stabilisation Dose (Week 6)*
Monotherapy with lamotrigine OR adjunctive therapy WITHOUT valproate and WITHOUT inducers of lamotrigine glucuronidation (see section 4.5):
This dosage regimen should be used with other medicinal products that do not significantly inhibit or induce lamotrigine glucuronidation	25mg/day (once a day)	50mg/day (once a day or two divided doses	100mg/day (once a day or two divided doses)	200mg/day – usual target dose for optimal response (once a day or two divided doses) Doses In the range 100 - 400mg/day used in clinical trials
Adjunctive therapy WITH valproate (inhibitor of lamotrigine glucuronidation - see section 4.5):
This dosage regimen should be used with valproate regardless of any concomitant medicinal products	12.5mg/day (given as 25mg on alternate days)	25mg/day (once a day)	50mg/day (once a day or two divided doses)	100mg/day – usual target dose for optimal response (once a day or two divided doses) Maximum dose of 200mg/day can be used depending on clinical response
Adjunctive therapy WITHOUT valproate and WITH inducers of lamotrigine glucuronidation (see section 4.5):
This dosage regimen should be used without valproate but with: phenytoin carbamazepine phenobarbital primidone rifampicin lopinavir/ritonavir	50mg/day (once a day)	100mg/day (two divided doses)	200mg/day (two divided doses)	300mg/day in week 6, if necessary increasing to usual target dose of 400mg/day in week 7, to achieve optimal response (two divided doses)
In patients taking medicinal products where the pharmacokinetic interaction with lamotrigine is currently not known (see section 4.5), the dose escalation as recommended for lamotrigine with concurrent valproate, should be used.

* The Target stabilisation dose will alter depending on clinical response

Table 4: Adults aged 18 years and above - maintenance stabilsation total daily dose following withdrawal of concomitant medicinal products in treatment of bipolar disorder

Once the target daily maintenance stabilisation dose has been achieved, other medicinal products may be withdrawn as shown below.

Treatment Regimen	Current lamotrigine stabilisation dose (prior to withdrawal)	Week 1 (beginning with withdrawal)	Week 2	Week 3 onwards *
Withdrawal of valproate (inhibitor of lamotrigine glucuronidation - see section 4.5), depending on original dose of lamotrigine:
When valproate is withdrawn, double the stabilisation dose, not exceeding an increase of more than 100mg/week	100mg/day	200mg/day	Maintain this dose (200mg/day) (two divided doses)
200mg/day	300mg/day	400mg/day	Maintain this dose (400mg/day)
Withdrawal of inducers of lamotrigine glucuronidation (see section 4.5), depending on original dose of lamotrigine:
This dosage regimen should be used when the following are withdrawn: phenytoin carbamazepine phenobarbital primidone rifampicin lopinavir/ritonavir	400mg/day	400mg/day	300mg/day	200mg/day
300mg/day	300mg/day	225mg/day	150mg/day
200mg/day	200mg/day	150mg/day	100mg/day
Withdrawal of medicinal products that do NOT signifcantly inhibit or induce lamotrigine glucuronidation (see section 4.5):
This dosage regimen should be used when other medicinal products that do not significantly inhibit or induce lamotrigine glucuronidation are withdrawn	Maintain target dose achieved in dose escalation (200mg/day; two divided doses) (dose range 100 - 400mg/day)
In patients taking medicinal products where the pharmacokinetic interaction with lamotrigine is currently not known (see section 4.5), the treatment regimen as recommended for lamotrigine with concurrent valproate should be used.

* Dose may be increased to 400mg/day as needed

Table 5: Adults aged 18 years and above - adjustment of lamotrigine daily dosing following the addition of other medicinal products in treatment of bipolar disorder

There is no clinical experience in adjusting the lamotrigine daily dose following the addition of other medicinal products. However, based on interaction studies with other medicinal products, the following recommendations can be made:

Treatment Regimen	Current lamotrigine stabilisation dose (prior to addition)	Week 1 (beginning with addition)	Week 2	Week 3 onwards
Addition of valproate (inhibitor of lamotrigine glucuronidation - see section 4.5), depending on original dose of lamotrigine:
This dosage regimen should be used when valproate is added regardless of any concomitant medicinal products	200mg/day	100mg/day	Maintain this dose (100mg/day)
300mg/day	150mg/day	Maintain this dose (150mg/day)
400mg/day	200mg/day	Maintain this dose (200mg/day)
Addition of inducers of lamotrigine glucuronidation in patients NOT taking valproate (see section 4.5), depending on original dose of lamotrigine:
This dosage regimen should be used when the following are added without valproate: phenytoin carbamazepine phenobarbital primidone rifampicin lopinavir/ritonavir	200mg/day	200mg/day	300mg/day	400mg/day
150mg/day	150mg/day	225mg/day	300mg/day
100mg/day	100mg/day	150mg/day	200mg/day
Addition of medicinal products that do NOT significantly inhibit or induce lamotrigine glucuronidation (see section 4.5):
This dosage regimen should be used when other medicinal products that do not significantly inhibit or induce lamotrigine glucuronidation are added	Maintain target dose achieved in dose escalation (200mg/day; dose range 100-400mg/day)
In patients taking medicinal products where the pharmacokinetic interaction with lamotrigine is currently not known (see section 4.5), the treatment regimen as recommended for lamotrigine with concurrent valproate, should be used.

Discontinuation of Lamotrigine Tablets in patients with bipolar disorder

In clinical trials, there was no increase in the incidence, severity or type of adverse reactions following abrupt termination of lamotrigine versus placebo. Therefore, patients may terminate Lamotrigine Tablets without a step-wise reduction of dose.

Children and adolescents below 18 years

Lamotrigine Tablets is not recommended for use in children below 18 years of age due to a lack of data on safety and efficacy (see section 4.4).

General dosing recommendations for Lamotrigine Tablets in special patient populations

Women taking hormonal contraceptives

The use of an ethinyloestradiol/levonorgestrel (30µg/150µg) combination increases the clearance of lamotrigine by approximately two-fold, resulting in decreased lamotrigine levels. Following titration, higher maintenance doses of lamotrigine (by as much as two-fold) may be needed to attain a maximal therapeutic response. During the pill-free week, a two-fold increase in lamotrigine levels has been observed. Dose-related adverse events cannot be excluded. Therefore, consideration should be given to using contraception without a pill-free week, as first-line therapy (for example, continuous hormonal contraceptives or non-hormonal methods; see sections 4.4 and 4.5).

Starting hormonal contraceptives in patients already taking maintenance doses of lamotrigine and NOT taking inducers of lamotrigine glucuronidation

The maintenance dose of lamotrigine will in most cases need to be increased by as much as two-fold (see sections 4.4 and 4.5). It is recommended that from the time that the hormonal contraceptive is started, the lamotrigine dose is increased by 50 to 100mg/day every week, according to the individual clinical response. Dose increases should not exceed this rate, unless the clinical response supports larger increases. Measurement of serum lamotrigine concentrations before and after starting hormonal contraceptives may be considered, as confirmation that the baseline concentration of lamotrigine is being maintained. If necessary, the dose should be adapted. In women taking a hormonal contraceptive that includes one week of inactive treatment ("pill-free week"), serum lamotrigine level monitoring should be conducted during week 3 of active treatment, i.e. on days 15 to 21 of the pill cycle. Therefore, consideration should be given to using contraception without a pill-free week, as first-line therapy (for example, continuous hormonal contraceptives or non-hormonal methods; see sections 4.4 and 4.5).

Stopping hormonal contraceptives in patients already taking maintenance doses of lamotrigine and NOT taking inducers of lamotrigine glucuronidation

The maintenance dose of lamotrigine will in most cases need to be decreased by as much as 50% (see sections 4.4 and 4.5). It is recommended to gradually decrease the daily dose of lamotrigine by 50-100mg each week (at a rate not exceeding 25% of the total daily dose per week) over a period of 3 weeks, unless the clinical response indicates otherwise. Measurement of serum lamotrigine concentrations before and after stopping hormonal contraceptives may be considered, as confirmation that the baseline concentration of lamotrigine is being maintained. In women who wish to stop taking a hormonal contraceptive that includes one week of inactive treatment ("pill-free week"), serum lamotrigine level monitoring should be conducted during week 3 of active treatment, i.e. on days 15 to 21 of the pill cycle. Samples for assessment of lamotrigine levels after permanently stopping the contraceptive pill should not be collected during the first week after stopping the pill.

Starting lamotrigine in patients already taking hormonal contraceptives

Dose escalation should follow the normal dose recommendation described in the tables.

Starting and stopping hormonal contraceptives in patients already taking maintenancedoses of lamotrigine and TAKING inducers of lamotrigine glucuronidation

Adjustment to the recommended maintenance dose of lamotrigine may not be required.

If the doses calculated for children, according to bodyweight, do not equate to whole tablets the dose to be administered is that equal to the lower number of whole tablets.

Elderly (above 65 years)

No dosage adjustment from recommended schedule is required. The pharmacokinetics of lamotrigine in this age group do not differ significantly from a non elderly adult population (see section 5.2).

Renal impairment

Caution should be exercised when administering Lamotrigine Tablets to patients with renal failure. For patients with end-stage renal failure, initial doses of lamotrigine should be based on patients' concomitant medicinal products; reduced maintenance doses may be effective for patients with significant renal functional impairment (see sections 4.4 and 5.2).

Hepatic impairment

Initial, escalation and maintenance doses should generally be reduced by approximately 50% in patients with moderate (Child-Pugh grade B) and 75% in severe (Child-Pugh grade C) hepatic impairment. Escalation and maintenance doses should be adjusted according to clinical response (see section 5.2).

4.3 Contraindications

Lamotrigine is contraindicated in individuals with known hypersensitivity to lamotrigine.

Lamotrigine is cleared primarily by metabolism in the liver. No studies have been carried out in patients with significant impairment of hepatic function. Until such data become available Lamotrigine cannot be recommended in this condition.

4.4 Special Warnings And Precautions For Use

Skin rash

There have been reports of adverse skin reactions, which have generally occurred within the first 8 weeks after initiation of lamotrigine treatment. The majority of rashes are mild and self limiting, however rarely, serious potentially life threatening skin rashes including Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported (see section 4.8).

In adults enrolled in studies utilizing the current lamotrigine dosing recommendations the incidence of serious skin rashes is approximately 1 in 500 in epilepsy patients (see section 4.8).

The approximate incidence of serious skin rashes reported as SJS in adults and children over the age of 12 is 1 in 1000. The risk is higher in children under the age of 12 than in adults. Available data from a number of studies suggest the incidence in children under the age of 12 requiring hospitalisation due to rash ranges from 1 in 300 to 1 in 100 (see section 4.8).

In children, the initial presentation of a rash can be mistaken for an infection, physicians should consider the possibility of a drug reaction in children that develop symptoms of rash and fever during the first eight weeks of therapy.

Additionally the overall risk of rash appears to be strongly associated with:-

-	High initial doses of lamotrigine and exceeding the recommended dose escalation of lamotrigine therapy (see section 4.2).
-	Concomitant use of valproate, which increases the mean half life of lamotrigine nearly two fold (see section 4.2).

Approximately half of these cases have been reported as Stevens-Johnson syndrome (1 in 1000). In clinical trials in patients with bipolar disorder, the incidence of serious rash is approximately 1 in 1000.

The risk of serious skin rashes in children is higher than in adults. Available data from a number of studies suggest the incidence of rashes associated with hospitalisation in epileptic children is from 1 in 300 to 1 in 100.

In children, the initial presentation of a rash can be mistaken for an infection, physicians should consider the possibility of a reaction to lamotrigine treatment in children that develop symptoms of rash and fever during the first eight weeks of therapy.

Additionally the overall risk of rash appears to be strongly associated with:

− high initial doses of lamotrigine and exceeding the recommended dose escalation of lamotrigine therapy (see section 4.2)

− concomitant use of valproate (see section 4.2).

Caution is also required when treating patients with a history of allergy or rash to other AEDs as the frequency of non-serious rash after treatment with lamotrigine was approximately three times higher in these patients than in those without such history.

All patients (adults and children) who develop a rash should be promptly evaluated and lamotrigine withdrawn immediately unless the rash is clearly not drug related to lamotrigine treatment. It is recommended that Lamotrigine Tablets not be restarted in patients who have discontinued due to rash associated with prior treatment with lamotrigine unless the potential benefit clearly outweighs the risk.

Rash has also been reported as part of a hypersensitivity syndrome associated with a variable pattern of systemic symptoms including fever, lymphadenopathy, facial oedema and abnormalities of the blood and liver (see section 4.8). The syndrome shows a wide spectrum of clinical severity and may, rarely, lead to disseminated intravascular coagulation (DIC) and multiorgan failure. It is important to note that early manifestations of hypersensitivity (e.g., fever, lymphadenopathy) may be present even though rash is not evident. Patients should be warned to seek immediate medical advice if signs and symptoms develop. If such signs and symptoms are present the patient should be evaluated immediately and lamotrigine discontinued if an alternative aetiology cannot be established.

Clinical worsening and suicide risk

Suicidal ideation and behaviour have been reported in patients treated with AEDs in several indications. A meta-analysis of randomised placebo-controlled trials of AEDs has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for lamotrigine.

Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.

In patients with bipolar disorder, worsening of depressive symptoms and/or the emergence of suicidality may occur whether or not they are taking medications for bipolar disorder, including Lamotrigine Tablets. Therefore patients receiving Lamotrigine Tablets for bipolar disorder should be closely monitored for clinical worsening (including development of new symptoms) and suicidality, especially at the beginning of a course of treatment, or at the time of dose changes. Certain patients, such as those with a history of suicidal behaviour or thoughts, young adults, and those patients exhibiting a significant degree of suicidal ideation prior to commencement of treatment, may be at a greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment.

Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients who experience clinical worsening (including development of new symptoms) and/or the emergence of suicidal ideation/behaviour, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms.

Hormonal contraceptives

Effects of hormonal contraceptives on lamotrigine efficacy

The use of an ethinyloestradiol/levonorgestrel (30µg/150µg) combination increases the clearance of lamotrigine by approximately two-fold resulting in decreased lamotrigine levels (see section 4.5). A decrease in lamotrigine levels has been associated with loss of seizure control. Following titration, higher maintenance doses of lamotrigine (by as much as two-fold) will be needed in most cases to attain a maximal therapeutic response. When stopping hormonal contraceptives, the clearance of lamotrigine may be halved. Increases in lamotrigine concentrations may be associated with dose-related adverse events.

Patients should be monitored with respect to this.

In women not already taking an inducer of lamotrigine glucuronidation and taking a hormonal contraceptive that includes one week of inactive treatment (for example "pill-free week"), gradual transient increases in lamotrigine levels will occur during the week of inactive treatment (see section 4.2). Variations in lamotrigine levels of this order may be associated with adverse effects. Therefore, consideration should be given to using contraception without a pill-free week, as first-line therapy (for example, continuous hormonal contraceptives or non-hormonal methods).

The interaction between other oral contraceptive or HRT treatments and lamotrigine have not been studied, though they may similarly affect lamotrigine pharmacokinetic parameters.

Effects of lamotrigine on hormonal contraceptive efficacy

An interaction study in 16 healthy volunteers has shown that when lamotrigine and a hormonal contraceptive (ethinyloestradiol/levonorgestrel combination) are administered in combination, there is a modest increase in levonorgestrel clearance and changes in serum FSH and LH (see section 4.5). The impact of these changes on ovarian ovulatory activity is unkown. However, the possibility of these changes resulting in decreased contraceptive efficacy in some patients taking hormonal preparations with lamotrigine cannot be excluded. Therefore, women should have a review of their contraception when starting lamotrigine, and the use of alternative non-hormonal methods of contraception should be encouraged. A hormonal contraceptive should only be used as the sole method of contraception if there is no other alternative. If the oral contraceptive pill is chosen as the sole method of contraception, women should be advised to promptly notify their physician if they experience changes in menstrual pattern (e.g. breakthrough bleeding) while taking lamotrigine as this may be an indication of decreased contraceptive efficacy. Women taking lamotrigine should notify their physician if they plan to start or stop use of oral contraceptives or other female hormonal preparations.

Dihydrofolate reductase

Lamotrigine is a weak inhibitor of dihydrofolate reductase hence there is a possibility of interference with folate metabolism during long-term therapy (see section 4.6). However, during prolonged human dosing, lamotrigine did not induce significant changes in the haemoglobin concentration, mean corpuscular volume, or serum or red blood cell folate concentrations up to 1 year or red blood cell folate concentrations for up to 5 years.

Renal failure

In single dose studies in subjects with end stage renal failure, plasma concentrations of lamotrigine were not significantly altered. However, accumulation of the glucuronide metabolite is to be expected; caution should therefore be exercised in treating patients with renal failure.

Patients taking other preparations containing lamotrigine

Lamotrigine Tablets should not be administered to patients currently being treated with any other preparation containing lamotrigine without consulting a doctor.

Development in children

There are no data on the effect of lamotrigine on growth, sexual maturation and cognitive, emotional and behavioural developments in children.

Precautions relating to epilepsy

As with other AEDs, abrupt withdrawal of lamotrigine may provoke rebound seizures. Unless safety concerns (for example rash) require an abrupt withdrawal, the dose of lamotrigine should be gradually decreased over a period of 2 weeks.

There are repo