Winsulin-N/Winsulin-30/70/Winsulin-R

Winsulin-N: Human insulin [isophane (NPH) recombinant DNA].
Winsulin-30/70: Human insulin (regular human insulin 30%, isophane insulin 70%).
Winsulin-R: Human insulin (recombinant DNA origin).

Winsulin-N/Winsulin-30/70/Winsulin-R in a 3-ml cartridge, to be used with Insulin Pen (see Instruction for Use under Cautions for Usage).
Winsulin-N/Winsulin-30/70/Winsulin-R in a 10-ml vial, to be used with insulin syringe with a corresponding unit scale (see Instruction for Use under Cautions for Usage).
Winsulin-N: Each ml of Winsulin-N contains Insulin Human USP 100.0 IU.
Winsulin-30/70: Winsulin-N/Winsulin-30/70 is a white sterile suspension which on standing deposits white sediment and leaves a colorless of almost colorless supernatant liquid; the sediment is readily resuspended by gentle shaking.
Winsulin-N contains isophane insulin human suspension-NPH (recombinant DNA origin); while Winsulin-30/70 is a mixture of Insulin human regular 30% with isophane insulin human suspension-NPH 70% (recombinant DNA origin). These are synthesized in a special non-disease-producing laboratory strain of the yeast Hansenula polymorpha. This special host cell line has been genetically altered by the addition of the gene for human insulin production. These human insulin are structurally identical to the insulin produced by the human pancreas.
Winsulin-N is a crystalline suspension of monocomponent human insulin with protamine and zinc providing an intermediate-acting insulin with a slow onset of action and a longer duration of activity than that of regular insulin. The onset of action is 1-2 hours, peak effect is seen at 6-12 hours and the duration of effect is about 16-18 hours.
Winsulin-N provides an intermediate-acting insulin with a duration of activity about 18-24 hours which is longer than regular insulin and an onset of action is rapid similar to regular insulin (1-2 hours).
Winsulin-30/70 provides an intermediate-acting insulin with a duration of activity about 16-18 hours which is longer than regular insulin and an onset of action is rapid similar to regular insulin (0.5 hours).
Winsulin-N/Winsulin-30/70 is a sterile suspension and is for subcutaneous injection only. It should not be used intravenously or intramuscularly.
Each ml of Winsulin-30/70 contains Insulin Human USP 100.0 (30% Insulin Human Regular and 70% Isophane Insulin).
Winsulin-R: Winsulin-R is a clear colorless solution which has a short duration of action.
Winsulin-R contains Insulin human Regular (recombinant DNA origin). It is synthesized in a special non-disease-producing laboratory strain of the yeast Hansenula polymorpha. This special host cell line has been genetically altered by the addition of the gene for human insulin production. This human insulin is structurally identical to the insulin produced by the human pancreas.
Insulin human Regular contains zinc crystals dissolved in a clear solution. It is a sterile solution for parenteral use. It can be subcutaneously, intravenously or intramuscularly.
Each ml of Winsulin-R contains Insulin Human USP 100.0 IU.

Pharmacodynamics: Mechanism of Action: Like all other insulins, the glucose lowering effect of Insulin isophane insulin human suspension-NPH/Winsulin-30/70/Insulin human Regular is due to the facilitated uptake of glucose in body tissues. This uptake occurs following the binding of insulin to its receptors present in the muscle and adipose tissue. The blood glucose lowering effect of insulin also occurs due to the simultaneous inhibition of glucose output from the liver.
Pharmacokinetics: Insulin has a half-life of a few minutes in the blood stream. Consequently, the time course of action of any insulin may vary considerably in different individuals or at different times in the same individual. As with all insulin preparations, the onset of action, intensity and duration of action of isophane insulin human suspension-NPH/Winsulin-30/70/Insulin human Regular is dependent on the dose, site of injection, blood supply, temperature and physical activity.
An average action profile after subcutaneous injection indicates: Onset: within 1-2 hours (Winsulin-N), 0.5 hours (Winsulin-30/70), within 30 minutes (Winsulin-R); Peak levels attained: between 6-12 hours (Winsulin-N), 2-12 hours (Winsulin-30/70), between 1-3 hours (Winsulin-R); Duration of action: approximately 16-18 hours (Winsulin-N/Winsulin-30/70), approximately 6-8 hours (Winsulin-R).

Isophane insulin human suspension-NPH/Winsulin-30/70/Winsulin-R is use for controlling blood sugar level (glycemic control) in patients with diabetes mellitus.

Recommended dose: The dosage of isophane insulin human suspension-NPH/Winsulin-30/70/Insulin human Regular is determined by the physician, as per the needs of the patient. The average range of total daily insulin requirement for maintenance in Type 1 diabetic patients ranges between 0.5 and 1.0 IU/kg. Further, in insulin resistance and patients with Type 2 diabetes, the daily requirement of insulin may be substantially higher.
Mode of Administration: Isophane insulin human suspension-NPH/Winsulin-30/70/Insulin human Regular is usually administered subcutaneously in the abdominal wall, the thigh, the gluteal region or the deltoid region. (Insulin suspensions must never be administered intravenously - for Isophane insulin human suspension-NPH/Winsulin-30/70 only).
To avoid lipodystrophy, the site of injection should be frequently changed and any injection of insulin should be followed by a meal or snack containing carbohydrates within 30 minutes. Adjustment of dosage may be necessary if patients undertake increased physical activity or change their usual diet.

Overdose and Treatment: Hypoglycemia may occur as a result of an excess of insulin relative to food intake, energy expenditure, or both. Mild episodes of hypoglycemia usually can be treated with oral sugar. It is therefore recommended that the diabetic patient constantly carry some sugar lumps, sweet biscuits, or sugary fruit juice. Adjustments in drug dosage, meal patterns, or exercise, may be needed.
More severe episodes of hypoglycemia with coma, seizure, or neurologic impairment. Glucose must also be given intravenously. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery.

Isophane insulin human suspension-NPH/Winsulin-30/70/Insulin human Regular is contraindicated in the following conditions: Hypoglycemia; Hypersensitivity to insulin or any other component of the formulation.

According to Thailand's Notification of Ministry of Public Health: This drug must be prescribed by physician only. If dizziness and fainting occur, consult the physician immediately.

Switching Patients to Different Type of Insulin: Transferring a patient to another type of insulin should be done under strict medical supervision. Changes in strength, brand (manufacturer), type (rapid acting insulin, intermediate acting insulin, long acting insulin etc), species (animal, Insulin human analog) and/or method of manufacturer (recombinant versus animal source insulin) may result in the need for a change in dose. Patients switching to Winsulin-N/Winsulin-30/70/Winsulin-R may require a change in dosage from that used with their usual insulin.
Laboratory Tests: As with all insulins, the therapeutic response to human insulin should be monitored by periodic blood glucose tests. Periodic measurement of glycosylated hemoglobin is recommended for the monitoring of long term glycemic control.
Renal Impairment: The requirements for insulin may be reduced in patients with renal impairment.
Hepatic Impairment: Although impaired hepatic function does not affect the absorption or disposition of isophane insulin human suspension-NPH/Winsulin-30/70/Insulin human Regular, careful glucose monitoring and dose adjustments of insulin may be necessary.
Effects on the ability to drive and use machines: The patient's ability to concentrate and react may be impaired as a result of hypoglycemia. This may constitute a risk in situations where these abilities are of special importance (e.g. driving a car or operation machinery). Patients should therefore be advised to avoid hypoglycemia during driving. This is particularly significant in particularly who have reduced awareness of the warning signs of hypoglycemia or have frequent episodes of hypoglycemia.

Pregnancy: There are no restrictions on the use of insulin during pregnancy since insulin does not cross the placental barrier. Published studies with human insulins suggest that optimizing overall glycemic control, including postprandial control, before conception and during pregnancy improves fetal outcome. Although the fetal complications of maternal hyperglycemia have been well documented, fetal toxicity also has been reported with maternal hypoglycemia. Insulin requirements usually fall during the first trimester and increase during the second and third trimesters. Careful monitoring of the patient is required throughout pregnancy. During the perinatal period, careful monitoring of infants born to mothers with diabetes is warranted.
Nursing Mothers: There are no restrictions on the use of insulin in lactating mothers as insulin treatment of nursing mothers does not involve any risk to the baby. However, caution should be exercised when administered to nursing mothers and the dosage of insulin may be reduced.

The most commonly seen adverse reaction with isophane insulin human suspension-NPH/Winsulin-30/70/Insulin human Regular are: Hypoglycemia: Hypoglycemia is one of the most common adverse effects seen with the use of any type of insulin. This can occur because of the following: Use of too much insulin; Missed meal/delayed meal; Intercurrent infection or illness; Strenuous exercise.
Diseases of the adrenal, pituitary, or thyroid gland, or progression of kidney or liver disease may also lead to hypoglycemia.
Concomitant administration with other drugs that lower blood glucose such as oral hypoglycemics, salicylates (for example, aspirin), sulfa antibiotics, and certain antidepressants may lead to hypoglycemia.
Concomitant consumption of alcoholic beverages may also lead to hypoglycemia.
Symptoms of mild to moderate hypoglycemia may occur suddenly and can include: Sweating; dizziness; palpitation; tremor; hunger; restlessness; tingling in the hands, feet, lips, or tongue: lightheadedness; inability to concentrate; headache; drowsiness; sleep disturbances; anxiety; blurred vision; slurred speech; depressive mood; irritability; abnormal behavior; unsteady movement; personality changes.
Signs of severe hypoglycemia can include: Disorientation, unconsciousness, seizures, death.
Therefore, it is important that assistance be obtained immediately.
Early warning symptoms of hypoglycemia may be different or less pronounced under certain conditions, such as long duration of diabetes, diabetic nerve disease, co-administration of medications such as beta-blockers, change in insulin preparations, or intensified control (3 or more insulin injections per day) of diabetes.
The use of preparations of isophane insulin human suspension-NPH/Winsulin-30/70/Insulin human Regular should minimize the incidence of adverse effects associated with the use of animal insulins.
Oedema: Oedema and refraction anomalies may occur upon initiation of insulin therapy. These symptoms are usually of a transitory nature.
Hyperglycemia and ketoacidosis: In patients with insulin-dependent diabetes, prolonged hyperglycemia can result in diabetic acidosis. The first symptoms of diabetic acidosis usually come on gradually, over a period of hours or days, and include a drowsy feeling, flushed face, thirst, loss of appetite, and fruity odor on the breath. With acidosis, urine tests show large amounts of glucose and acetone. Heavy breathing and a rapid pulse are more severe symptoms. If uncorrected, prolonged hyperglycemia or diabetic acidosis can result in loss of consciousness or death. Therefore, it is important that one should obtain medical assistance immediately.
Allergy: Allergy to Insulin: Local Allergy: Patients occasionally experience redness, swelling, and itching at the site of injection of insulin. This condition called local allergy, usually clears up in a few days to a few weeks. In some instances, this condition may be related to factors other than insulin, such as irritants in the skin cleansing agent.
Systemic Allergy: Less common, but potentially more serious, is generalized allergy to insulin, which may cause rash over the whole body, shortness of breath, wheezing, reduction in blood pressure, fast pulse, or sweating. Severe cases of generalized allergy may be life threatening.
Lipoatrophy and lipodystrophy: Lipodystrophy occurs at the site of injection after long usage. However, this is less common with the newer preparations of insulin.
Insulin resistance: When insulin requirement is increased (>200 IU/day), insulin resistance is said to have developed. The following are the different grades of insulin resistance: Acute: Acute insulin resistance develops rapidly and is usually a short term problem. It usually occurs due to an underlying infection, trauma, surgery and emotional stress. Treatment is to overcome the precipitating factor and to give high doses of regular insulin.
Chronic: This type of insulin resistance is generally seen in patients treated for years with conventional preparations of beef or pork insulins and it is more common in patients with Type 2 diabetes. Development of such a type of insulin resistance is an indication for switching patients to the newer preparations of insulin. After instituting the newer preparations, insulin requirement gradually declines over weeks and months and majority of patients stabilize at approximately 60 IU/day.

Insulin requirements may be increased by medications with hyperglycemic activity such as corticosteroids, isoniazid, certain lipid-lowering drugs (e.g. niacin), estrogens, oral contraceptives, phenothiazines, and thyroid replacement therapy.
Insulin requirements may be decreased in the presence of drugs with hypoglycemic activity, such as oral hypoglycemic agents, salicylates, sulfa antibiotics, certain antidepressants (monoamine oxidase inhibitors), certain angiotensin converting enzyme inhibitors, beta adrenergic blockers, inhibitors of pancreatic function (e.g. octreotide), and alcohol. Beta adrenergic blockers may mask the symptoms of hypoglycemia in some patients.

Instruction for Use: Winsulin-N/Winsulin-30/70: Cartridge: 1. Disinfect the rubber surface of the insulin cartridge with alcohol. Insert the cartridge in the Pen as shown in the Insulin Pen instruction manual. Before inserting the cartridge, inspect the cartridge of Winsulin-N/Winsulin-30/70 after removing from the sealed pack for any crystallization, clumping or discolouration. If present, discard and use a new cartridge.
2. Before inserting the cartridge into the Insulin Pen, roll it between the palms at least 10 times.
Then hold the cartridge at one end and move between position "A" to position "B" slowly so that the glass ball travels from one end of the cartridge to the other end.
This must be done at least 10 times until the liquid appears uniformly cloudy or milky. Discard the cartridge if clumps are seen after mixing.
3. If the cartridge is already inside the Insulin Pen, turn the Pen up and down gently at least 10 times until the liquid appears uniformly cloudy or milky. This has to be done before each injection.
4. After attaching the needle, dial 2 units on the dose selector to remove any air that may be inside the needle.
5. Wash hands and clean the skin with alcohol where the injection is to be made.
6. With one hand, lightly pinch up the skin, insert the needle as advised by the doctor or educator. Push and hold the release button of the Pen, Count to 10 and pull out the needle. Do not massage the area as this may cause back leakage of insulin.
7. Dispose off the needle in the recommended way.
Vial: It is important to use a syringe that is marked for the desired strength is U-100 insulin preparations. Failure to use the proper syringe can lead to a mistake in dosage, causing serious problems such as severe hypoglycemia or hyperglycemia.
1. Wash hands carefully. Shake or roll Winsulin-N/Winsulin-30/70 Insulin vial 10 times to completely mix the insulin.
2. Inspect the vial. Winsulin-N/Winsulin-30/70 should appear uniformly cloudy or milky. The insulin injection should not be used if there is anything unusual in appearance.
3. When using a new vial, flip off the plastic protective cap, but do not remove the stopper. The tip of the vial should be wiped with an alcohol swab.
4. Draw air into the syringe equal to the insulin dose.
5. Insert needle into vial through rubber top and push plunger to empty the air into the vial.
6. Turn the bottle and syringe upside down. Hold the bottle and syringe firmly in the hand and shake gently. Making sure that the tip of the needle is in the liquid, withdraw the correct dose of insulin into the syringe.
7. Before removing the needle from the vial, check the insulin syringe for air bubbles, which reduce the amount of insulin in it. If bubbles are present, hold the insulin straight up and tap its side until the bubbles float to the top. Push them out with the plunger and withdraw the correct dose again.
8. Lightly pinch up the skin, holding the syringe like a pencil.
9. Insert the needle into the skin and push the plunger slowly. Make sure that the needle is all the way in.10. Wait for 5 seconds and pull out the syringe. Do not rub the area.
Winsulin-R: Cartridge: 1. Disinfect the rubber surface of the insulin cartridge with alcohol. Insert the cartridge in the Pen as shown in the Insulin Pen instruction manual. Before inserting the cartridge, inspect the cartridge of Winsulin-R after removing from the sealed pack for any crystallization, clumping or discolouration. If present, discard and use a new cartridge.
2. After attaching the needle, dial 2 units on the dose selector to remove any air that may be inside the needle.
3. Wash hands and clean the skin with alcohol where the injection is to be made.
4. With one hand, lightly pinch up the skin; insert the needle as advised by a doctor or educator. Push and hold the release button of the Pen, count to 10 and pull out the needle. Do not massage the area as this may cause back leakage of insulin.
5. Dispose off the needle in the recommended way.
Vial: It is important to use a syringe that is marked for the desired strength, for U-100 insulin preparations. Failure to use the proper syringe can lead to a mistake in dosage, causing serious problems such as severe hypoglycemia or hyperglycemia.
1. When using a new vial, flip off the plastic protective cap, but do not remove the stopper. The tip of the vial should be wiped with an alcohol swab.
2. Draw air into the syringe equal to the insulin dose.
3. Insert needle into vial through rubber top and push plunger to empty the air into the vial.
4. Turn the bottle and syringe upside down. Hold the bottle and syringe firmly in hand and shake gently. Making sure that the tip of the needle is in the liquid, withdraw the correct dose of insulin into the syringe.
5. Before removing the needle from the vial, check the insulin syringe for air bubbles, which reduce the amount of insulin in it. If bubbles are present, hold the insulin straight up and tap its side until the bubbles float to the top. Push them out with the plunger and withdraw the correct dose again.
6. Lightly pinch up the skin, holding the syringe like a pencil.
7. Insert the needle into the skin and push the plunger slowly. Make sure that the needle is all the way in.
8. Wait for 5 seconds and pull out the syringe. Do not rub the area.

Winsulin-N/Winsulin-30/70/Winsulin-R: Cartridge: Winsulin-N/Winsulin-30/70/Winsulin-R Cartridge which is not in use should be stored in a refrigerator (2° to 8°C) but not allowed to freeze. When in use, Cartridge may be kept at room temperature (up to 25°C) for up to 4 weeks.
Do not expose to excessive heat or direct sunlight.
Insulin preparations, which have been frozen, must not be used.
Winsulin-N/Winsulin-30/70/Winsulin-R should not be used if it does not appear (uniformly cloudy or milky after shaking - for Winsulin-N/Winsulin-30/70 only) or (water-clear and colourless - for Winsulin-R only).
Remove the needle after each injection, otherwise temperature changes may cause liquid to leak out of the needle and the insulin concentration may increase.
Do not refill the cartridge.
Winsulin-N/Winsulin-30/70/Winsulin-R Cartridge should never be used after the expiry date.
Winsulin-N/Winsulin-30/70/Winsulin-R: Vial: Winsulin-N/Winsulin-30/70/Winsulin-R: Vial should be stored in a refrigerator (2° to 8°C) but not allowed to freeze.
When in use, vial may be kept at room temperature (up to 25°C) for up to 4 weeks.
Do not expose to excessive heat or direct sunlight.
Insulin preparations, which have been frozen, must not be used.
Winsulin-N/Winsulin-30/70/Winsulin-R should not be used if it does not appear (uniformly cloudy or milky after shaking - for Winsulin-N/Winsulin-30/70 only) or (water-clear and colourless - for Winsulin-R only).
Cold insulin can be irritating to inject. Thus, patients should be asked to roll the vial in their hands 10 times prior to drawing it up in the syringe (after allowing the vial to sit for 30 minutes at room temperature if the vial is stored in the refrigerator).
Winsulin-N/Winsulin-30/70/Winsulin-R Vial should never be used after the expiry date.

Insulin Preparations

A10AC01 - insulin (human) ; Belongs to the class of intermediate-acting insulins and analogues. Used in the treatment of diabetes.
A10AB01 - insulin (human) ; Belongs to the class of fast-acting insulins and analogues. Used in the treatment of diabetes.
A10AD01 - insulin (human) ; Belongs to the class of intermediate-acting combined with fast-acting insulins and analogues. Used in the treatment of diabetes.

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