Gensulin m50 (50/50)

Package leaflet: Information for the patient

Gensulin M40 (40/60), 100 IU/ml, suspension for injection
Gensulin M50 (50/50), 100 IU/ml, suspension for injection
Insulinum humanum

Please read all of this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet as you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Table of contents

1. What Gensulin M40 (40/60) (hereinafter Gensulin M40) and Gensulin M50 (50/50) (hereinafter Gensulin M50) are and what they are used for
2. Important information before using Gensulin M40 and M50
3. How to use Gensulin M40 and M50
4. Possible side effects
5. How to store Gensulin M40 and M50
6. Contents of the pack and other information

1. What Gensulin M40 and M50 are and what they are used for
Gensulin M40 and M50 contain human insulin produced by recombinant DNA technology using Escherichia coli bacteria, identical to insulin naturally produced by the human body.
Human insulin is used in the treatment of diabetes. Diabetes is caused by the inability of the pancreas to produce insulin in amounts sufficient to control blood glucose (blood sugar) levels. Gensulin M40 and M50 are used for long-term control of blood glucose levels. They are mixtures of fast-acting insulin and intermediate-acting insulin. The duration of action of this insulin has been prolonged by the addition of protamine sulfate to the suspension.
Your doctor may recommend using Gensulin M40 and M50 together with a longer-acting insulin. Do not change your insulin without consulting your doctor. When changing insulin, extreme caution is required. Each type of insulin has a different symbol and color on the packaging and cartridge to help distinguish them easily.

2. Important information before using Gensulin M40 and M50

Gensulin M40 and M50 in 3 ml cartridges are intended exclusively for subcutaneous injection using a reusable injection pen. If insulin must be administered by another method, consult your doctor.

When not to use Gensulin M40 and M50

• if symptoms indicating hypoglycemia (low blood glucose) are present. Information on managing mild hypoglycemia is provided later in this leaflet (see subsection A "Hypoglycemia" in section 4).
• if you are allergic to human insulin or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Before starting treatment with Gensulin M40 and M50, discuss it with your doctor, pharmacist, or nurse.
If your current treatment provides good glycemic control, warning signs of excessively low blood glucose levels may not be noticeable. Warning symptoms are listed later in this leaflet. You should carefully plan meal times, frequency of physical activity, and overall activity level. You should also monitor your blood sugar levels frequently by testing blood glucose.
Some individuals who experienced hypoglycemia (low blood glucose) after switching from animal insulin to human insulin have reported that the warning symptoms of hypoglycemia were less pronounced or completely different than before. If you experience frequent episodes of hypoglycemia or have difficulty recognizing the warning signs, consult your doctor.
Inform your diabetes nurse, doctor, or pharmacist if:

• you have recently been ill;
• you have kidney or liver disease;
• you have increased physical exertion.
  Your insulin requirement may also change after consuming alcohol. Inform your diabetes nurse, doctor, or pharmacist if you are planning to travel abroad. Time zone differences may require adjustments in injection and meal times.
  In some patients with type 2 diabetes who have long-term treatment and underlying heart disease or a history of stroke, cases of heart failure have been reported when pioglitazone was used concomitantly with insulin. Inform your doctor immediately if symptoms of heart failure occur, such as shortness of breath, sudden weight gain, or localized swelling.

Skin changes at the injection site
Rotate injection sites to prevent skin changes such as lumps under the skin (lipohypertrophy). Insulin injected into an area with lumps may not work properly (see "How to use Gensulin M40 and M50"). If you are currently injecting insulin into an area with lumps, consult your doctor before changing the site. Your doctor may recommend more frequent blood glucose monitoring and adjustment of insulin or other antidiabetic medication doses.

Gensulin M40 and M50 with other medicines
Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.

1. Your body's insulin requirement may change when used concomitantly with:
   • corticosteroids,
   • thyroid hormone replacement therapy,
   • oral antidiabetic drugs (medicines that lower blood glucose),
   • acetylsalicylic acid (aspirin),
   • growth hormone,
   • octreotide, lanreotide,
   • selective β2-adrenergic receptor agonists (e.g., ritodrine, salbutamol, terbutaline),
   • β-adrenergic blockers,
   • thiazides or certain antidepressants (monoamine oxidase inhibitors),
   • danazol,
   • certain angiotensin-converting enzyme inhibitors (e.g., captopril, enalapril) or angiotensin II receptor antagonists.

Pregnancy and breastfeeding
Insulin requirements usually decrease during the first three months of pregnancy and increase during the following six months. Women who are breastfeeding may require adjustments in insulin dosage or dietary habits.
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor or pharmacist before using this medicine.

Driving and operating machinery
Hypoglycemia (low blood glucose) may impair your concentration and reaction speed. Remember this in any situation where such impairment could endanger you or others (e.g., when driving or operating machinery).
Consult your diabetes nurse or doctor about driving if:

• you frequently experience hypoglycemia,
• you have weak or no warning signs of hypoglycemia.

Gensulin M40 and M50 contain sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, meaning it is considered "sodium-free".

3. How to use Gensulin M40 and M50

Always check the name and type of insulin on the label and cartridge packaging when
purchasing the medicine at the pharmacy. Make sure it is the Gensulin M40 and M50 medicine
prescribed by your doctor.
This medicine should always be used according to the instructions of your doctor or pharmacist. If in doubt,
consult your doctor or pharmacist. To avoid possible transmission of diseases, each cartridge may be used only by one person,
even if the needle has been changed.

Dosage
Your doctor will recommend the appropriate type of insulin, the dose, and the timing and frequency
of injections. These instructions are intended solely for the specific patient. You must strictly follow your doctor's advice and regularly visit the diabetes clinic.
Changing the type of insulin used (e.g., from animal insulin to human insulin) may
require a reduction or increase in dose. This change may affect only the first injection or may be introduced gradually over several weeks
or months.
Gensulin M40 and M50 in cartridges is intended exclusively for subcutaneous
injection using a reusable insulin pen. If insulin must be administered by another method, consult your doctor.

Preparing Gensulin M40 and M50
Before using Gensulin M40 and M50, you should

• check the outer packaging and cartridge label to confirm that the name and letter designation of the insulin received match the prescription provided by your doctor.
• check the expiration date on the packaging.

Instructions for use
Inject the insulin dose as directed by your doctor or diabetes nurse.
Always rotate injection sites to avoid thickening of the skin (see section 4. Possible side effects). It is best to inject insulin into the abdominal area, buttocks, front of the thigh, or upper arm.
Injection into the abdominal area results in faster absorption than injections into other sites.
Rotate injection sites so that the same site is not used more often than approximately once per month.
Remove the insulin from the refrigerator about ten minutes before administration to bring it to room temperature (if it is a newly started cartridge). A used cartridge should be stored at room temperature for up to 28 days.
During administration, follow hygiene rules: wash your hands before injecting and disinfect the injection site.
Before administration, carefully inspect the insulin cartridge.
The suspension of Gensulin M40 and M50 should be uniformly opaque (consistently cloudy or milky). Do not use the medicine if, after mixing, the contents of the cartridge remain clear or if a white sediment remains at the bottom. Do not use if, after mixing, white clumps float in the liquid or if solid white particles adhere to the walls, giving it a frosted appearance.
Pay special attention during insulin injection to ensure the needle does not enter a blood vessel.

Administration of Gensulin M40 and M50 in cartridges
The 3 ml cartridges of Gensulin M40 and M50 are intended exclusively for subcutaneous
injection using a reusable insulin pen.
Do not administer Gensulin M40 and M50 intravenously or intramuscularly.
If insulin must be administered by another method, consult your doctor.
The 3 ml cartridges are intended for use with a pen device marked with the CE symbol, in accordance with the manufacturer's instructions. Gensulin M40 and M50 cartridges should be used only with Bioton insulin pens to ensure accurate dosing.
For loading the pen, attaching the needle, and administering the insulin, strictly follow the instructions provided by the pen manufacturer included in the pen packaging.
The Gensulin M40 and M50 suspension must be mixed before each injection by gently rolling the cartridge up and down at least 10 times or rolling it between your palms until the liquid becomes uniform. Continue rotating until the suspension appears consistently cloudy or milky. The cartridges contain a small glass bead to assist in mixing the components. Do not shake vigorously, as this may cause foaming, which could interfere with accurate dosing.
The cartridge contents can be mixed without removing it from the pen.
The cartridge design prevents adding any other insulin to the cartridge. Used cartridges must not be refilled.

Use of a higher than recommended dose of Gensulin M40 and M50
If a higher than recommended dose of Gensulin M40 and M50 is administered, low blood glucose levels may occur. Check your blood glucose level (see section A, "Hypoglycaemia" in section 4).

Missing a dose of Gensulin M40 and M50
If a lower than recommended dose of Gensulin M40 and M50 is administered, high blood glucose levels may occur. Check your blood glucose level. Do not take a double dose to make up for a missed dose.

Interrupting treatment with Gensulin M40 and M50
If a lower than recommended dose of Gensulin M40 and M50 is administered, blood glucose levels may increase. Do not change the type of insulin you are using unless instructed by your doctor.

If you have any further questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although they do not occur in everyone.
Human insulin may cause hypoglycaemia (low blood glucose levels). See further information on
hypoglycaemia below under the section "Common problems in diabetes".
Possible adverse effects
Generalised allergic reaction is very rare (in less than 1 in 10,000 patients).
Symptoms include:

• drop in blood pressure
• difficulty breathing
• rapid heartbeat
• rash all over the body
• wheezing
• sweating

If any of these symptoms occur while using Gensulin M40 and M50, contact your doctor immediately.
Local allergic reaction is common (in less than 1 in 10 patients). Symptoms may include
redness, swelling or itching of the skin around the injection site. These symptoms usually
disappear after a few days or weeks. If any of the above symptoms occur, inform your doctor.
Skin changes at the injection site
If insulin is injected too frequently into the same site, fatty tissue may shrink (lipoatrophy) or
thicken (lipohypertrophy) (in no more than 1 in 100 patients).
Lumps under the skin may also be caused by the accumulation of a protein called amyloid (cutaneous amyloidosis; frequency unknown). Insulin injected into an area with lumps may not work properly. Always change the injection site—this will help prevent these skin changes.
Swelling (e.g. swelling of arms, ankles; fluid retention) has been reported, particularly at the start
of insulin treatment or during changes in therapy aimed at improving blood glucose control.
Common problems in diabetes
A. Hypoglycaemia
Hypoglycaemia (low blood glucose level) is a condition in which there is too little sugar in the blood. It may occur if the patient:

• takes too high a dose of Gensulin M40 and M50 or another insulin;
• skips or delays a meal, or changes their diet;
• exercises excessively or works physically hard just before or after a meal;
• is ill (especially with an illness involving diarrhoea or vomiting);
• changes in insulin requirements, or
• has worsening kidney or liver function.

Alcohol and certain medicines may affect blood glucose levels.
The first symptoms of low blood glucose usually appear quickly and include:

• fatigue
• nervousness or trembling
• headache
• rapid heartbeat
• nausea
• cold sweats

If you are unsure about recognising the warning signs of hypoglycaemia, avoid situations where you might endanger yourself or others (e.g. driving a car).
Do not use Gensulin M40 and M50 if you are experiencing symptoms of hypoglycaemia
(low blood glucose levels).
If blood glucose levels are low, eat glucose tablets, sugar, or drink a sweet beverage. Then eat a fruit, biscuits or a sandwich, as advised by your doctor, and rest. This is usually sufficient in cases of mild hypoglycaemia or minor insulin overdose. If the condition worsens, with shallow breathing and pale skin, contact your doctor immediately. An injection of glucagon may help in cases of moderately severe hypoglycaemia.
After glucagon injection, eat glucose tablets or sugar. If there is no improvement after glucagon administration, go to hospital. For information about glucagon, consult your doctor.
B. Hyperglycaemia and diabetic ketoacidosis
Hyperglycaemia (too high blood glucose level) means the body is not receiving enough insulin. Hyperglycaemia may be caused by:

• not taking Gensulin M40 and M50 or another insulin;
• injecting less insulin than prescribed by your doctor;
• eating very large meals compared to dietary requirements; or
• fever, infection, or stressful events.

Hyperglycaemia may lead to diabetic ketoacidosis. The first symptoms develop slowly over several hours or days. These symptoms include:

• drowsiness
• flushed face
• thirst
• loss of appetite
• fruity odour of breath
• nausea or vomiting

Severe symptoms include difficulty breathing and rapid pulse. Seek immediate medical help.
Untreated hypoglycaemia (low blood glucose) or hyperglycaemia (high blood glucose) may lead to serious complications and may cause headache, nausea, vomiting, dehydration, loss of consciousness, coma or even death.
Three simple ways to avoid hypoglycaemia or hyperglycaemia:
Always carry a spare insulin pen and cartridge of
Gensulin M40 and M50
Always carry something that informs others that you have diabetes.
Always carry sugar lumps.
C. Illness
During illness, especially when associated with nausea or vomiting, the body's insulin requirements may change. People with diabetes need insulin even when they are not eating normal meals. Perform urine or blood tests, follow general illness management guidelines, and contact your diabetes nurse or doctor.
Since insulin has been marketed, the following adverse effects have also been reported:

• oedema, particularly when previously poor metabolic control has been improved by intensive insulin therapy,
• weight gain,
• injection site reactions such as: discolouration, bleeding, induration, nodule or infiltration, pain, rash, urticaria or pustules,
• itching, including generalised itching,
• dizziness.

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C, 02-222 Warsaw;
Tel.: +48 22 49 21 301; Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported directly to the marketing authorisation holder.
Reporting adverse effects helps provide more information on the safety of this medicine.

5. How to store Gensulin M40 and M50

Keep the medicine out of sight and reach of children.
Store at a temperature of 2°C to 8°C. Do not freeze.
After first opening the immediate packaging, the medicine may be stored at a temperature up to 25°C for 28 days. Protect from light.
Do not store used or currently used cartridges in the refrigerator. They may be carried at room temperature. The medicinal product Gensulin M40 and M50 should be protected from high temperatures.
Do not use this medicine after the expiry date stated on the label and outer packaging of the Gensulin M40 and M50 cartridge after "EXP". The expiry date refers to the last day of the stated month.
Do not use this medicine if you notice clumps or white particles adhering to the bottom or sides of the cartridge, or if the glass appears dull or cloudy. The appearance of insulin should be checked before each injection.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Gensulin M40 and M50 contains

• The active substance is human insulin produced by recombinant biotechnology. 1 ml of suspension contains 100 IU of human insulin. Each cartridge contains 3 ml, corresponding to a dose of 300 IU of human insulin.
• Other components (excipients):
  Gensulin M40: metacresol, glycerol, phenol, protamine sulfate, zinc oxide, sodium dihydrogen phosphate dodecahydrate, hydrochloric acid, sodium hydroxide, water for injections
  Gensulin M50: metacresol, glycerol, phenol, protamine sulfate, zinc oxide, sodium dihydrogen phosphate dodecahydrate, hydrochloric acid, sodium hydroxide, water for injections

What Gensulin looks like and contents of the pack
Gensulin M40:
A sterile suspension of human insulin with pH 7–7.6, containing 40% soluble insulin and 60% isophane insulin.
Gensulin M50:
A sterile suspension of human insulin with pH 7–7.6, containing 50% soluble insulin and 50% isophane insulin.

Packaging
Gensulin M40:

• 5 glass cartridges for injection devices, containing 3 ml of Gensulin M40, packed in a cardboard box.
• 10 glass cartridges for injection devices, containing 3 ml of Gensulin M40, packed in a cardboard box.
  Gensulin M50:
• 5 glass cartridges for injection devices, containing 3 ml of Gensulin M50, packed in a cardboard box.
• 10 glass cartridges for injection devices, containing 3 ml of Gensulin M50, packed in a cardboard box.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Bioton S.A.
ul. Starościńska 5
02-516 Warsaw, Poland
Manufacturer
Bioton S.A.
Macierzysz, ul. Poznańska 12
05-850 Ożarów Mazowiecki, Poland

For further information on this medicinal product, please contact the Marketing Authorisation Holder:
Bioton S.A.
ul. Starościńska 5
02-516 Warsaw, Poland
Tel: +48 (22) 721 40 00
[email protected]