Metformin and repaglinide

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Metformin and repaglinide is usually taken 2 or 3 times daily, within 15 minutes before eating a meal. Follow your doctor's instructions. If you skip a meal, do not take your dose of metformin and repaglinide. Wait until your next meal.

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

Low blood sugar (hypoglycemia) can happen to everyone who has diabetes. Symptoms include headache, hunger, sweating, confusion, irritability, dizziness, or feeling shaky. Always keep a source of sugar with you in case you have low blood sugar. Sugar sources include fruit juice, hard candy, crackers, raisins, and non-diet soda. Be sure your family and close friends know how to help you in an emergency.

If you have severe hypoglycemia and cannot eat or drink, use a glucagon injection. Your doctor can prescribe a glucagon emergency injection kit and tell you how to use it.

Check your blood sugar carefully during times of stress, travel, illness, surgery or medical emergency, vigorous exercise, or if you drink alcohol or skip meals. These things can affect your glucose levels and your dose needs may also change. Do not change your medication dose or schedule without your doctor's advice.

Your doctor may have you take extra vitamin B12 while you are taking metformin and repaglinide. Take only the amount of vitamin B12 that your doctor has prescribed.

Metformin and repaglinide is only part of a complete treatment program that may also include diet, exercise, weight control, and special medical care. Follow your doctor's instructions very closely.

Store at room temperature away from moisture, heat, and light. Keep the bottle tightly closed when not in use.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. A metformin and repaglinide overdose can cause life-threatening hypoglycemia. Symptoms of severe hypoglycemia include extreme weakness, blurred vision, sweating, trouble speaking, tremors, stomach pain, confusion, and seizure (convulsions).

Avoid drinking alcohol. It lowers blood sugar and may increase your risk of lactic acidosis while taking metformin and repaglinide.

Usual Adult Dose for Diabetes Type 2:

Individualize based on current therapy, effectiveness, and tolerability

Initial dose:
Patients inadequately controlled on metformin monotherapy: repaglinide 1 mg/metformin 500 mg orally twice a day with meals
Patients inadequately controlled on meglitinide monotherapy: current meglitinide dose with metformin 500 mg orally twice a day with meals
Patients receiving individual components concomitantly: current or similar dose of individual components without exceeding current dose

Titrate gradually based on glycemic control and tolerability
Maximum single dose: repaglinide 4 mg/metformin 1000 mg
Maximum daily dose: repaglinide 10 mg/metformin 2500 mg

Comments:
-To be given 2 to 3 times a day within 15 minutes prior to meal; if a meal is skipped, a dose should not be given for that meal.
-Patients who have not been previously treated with a meglitinide should be started on the lowest dose of repaglinide to reduce the risk of hypoglycemia.
-Blood glucose monitoring should be performed to assess therapeutic response.

Use: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are already being treated with a meglitinide and metformin or who have inadequate glycemic control on a meglitinide alone or metformin alone.

Applies to metformin / repaglinide: oral tablet

Along with its needed effects, metformin / repaglinide 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 while taking metformin / repaglinide:

• Anxiety
• blurred vision
• body aches or pain
• chills
• cold sweats
• coma
• confusion
• cool, pale skin
• cough
• depression
• difficulty with breathing
• dizziness
• ear congestion
• fast heartbeat
• fever
• headache
• increased hunger
• loss of voice
• nasal congestion
• nausea
• nervousness
• nightmares
• runny nose
• seizures
• shakiness
• slurred speech
• sneezing
• sore throat
• unusual tiredness or weakness

Some side effects of metformin / repaglinide 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:

• Diarrhea
• vomiting

Applies to metformin / repaglinide: oral tablet

Gastrointestinal

Repaglinide-Metformin:
Very common (10% or more): Gastrointestinal system disorder (33%), diarrhea (19%), nausea (15%)

Repaglinide:
Very common (10% or more): Gastrointestinal system disorder (36%)
Common (1% to 10%): Diarrhea, nausea
Postmarketing reports: Pancreatitis

Metformin:
Very common (10% or more): Gastrointestinal system disorder (48%), diarrhea (30%)
Common (1% to 10%): Nausea[Ref]

Hepatic

Repaglinide:
Postmarketing reports: Severe hepatic dysfunction including jaundice and hepatitis[Ref]

Nervous system

Frequency not reported: Headache[Ref]

Respiratory

Repaglinide-Metformin:
Very common (10% or more): Upper respiratory tract infection (11%)

Repaglinide:
Very common (10% or more): Upper respiratory tract infection (11%)

Metformin:
Common (1% to 10%): Upper respiratory tract infection (11%)[Ref]

Hematologic

Repaglinide:
Postmarketing reports: Hemolytic anemia[Ref]

Dermatologic

Repaglinide:
Postmarketing reports: Stevens-Johnson syndrome, alopecia[Ref]

Cardiovascular

Cardiovascular events were evaluated in trials comparing repaglinide to sulfonylureas. Serious cardiovascular events including ischemia with this drug were higher at 4% (51/1228) than for sulfonylurea drugs (3%; 13/498). No excess mortality was associated with this increase. Selected cardiovascular events including hypertension, abnormal EKG, MI, arrhythmias, and palpitations were observed at 1% or less and no more frequently with this drug than with comparator drugs.

Across 7 repaglinide clinical trials, 6 serious events of myocardial ischemia occurred in combination use with NPH-insulin compared with 1 event in patients using insulin alone. Repaglinide should not be used in combination with NPH insulin.

Repaglinide:
Common (1% to 10%): myocardial ischemia, angina, chest pain
Frequency not reported: Hypertension, abnormal EKG, MI, arrhythmias, palpitations

General

The most frequently reported adverse reactions included hypoglycemia and headache.

Metabolic

Repaglinide-Metformin:
Very common (10% or more): Symptomatic hypoglycemia (33%)

Repaglinide:
Very common (10% or more): Symptomatic hypoglycemia (11%)

Metformin:
Common (1% to 10%): Subnormal vitamin B12 levels
Rare (less than 0.1%): Lactic acidosis

Some side effects of metformin / repaglinide may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Individualize based on current therapy, effectiveness, and tolerability

Initial dose:
Patients inadequately controlled on metformin monotherapy: repaglinide 1 mg/metformin 500 mg orally twice a day with meals
Patients inadequately controlled on meglitinide monotherapy: current meglitinide dose with metformin 500 mg orally twice a day with meals
Patients receiving individual components concomitantly: current or similar dose of individual components without exceeding current dose

Titrate gradually based on glycemic control and tolerability
Maximum single dose: repaglinide 4 mg/metformin 1000 mg
Maximum daily dose: repaglinide 10 mg/metformin 2500 mg

Comments:
-To be given 2 to 3 times a day within 15 minutes prior to meal; if a meal is skipped, a dose should not be given for that meal.
-Patients who have not been previously treated with a meglitinide should be started on the lowest dose of repaglinide to reduce the risk of hypoglycemia.
-Blood glucose monitoring should be performed to assess therapeutic response.

Use: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are already being treated with a meglitinide and metformin or who have inadequate glycemic control on a meglitinide alone or metformin alone.

Hepatic impairment: Avoid use