Package leaflet: Information for the patient

Polhumin MIX-2, 100 IU/ml, injection suspension
Insulinum humanum
Please read the entire leaflet carefully before use, as it contains
important information for the patient.

Keep this leaflet, so that you can read it again if necessary.
If you have any questions, please consult your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm another person, even if their symptoms are the same.
If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents:

What Polhumin MIX-2 is and what it is used for
Important information before using Polhumin MIX-2
How to use Polhumin MIX-2
Possible side effects
How to store Polhumin MIX-2
Contents of the pack and other information

1. What Polhumin MIX-2 is and what it is used for

Polhumin MIX-2 is human insulin used in the treatment of diabetes. This insulin is produced using genetic engineering techniques (recombinant DNA) in Escherichia coli bacteria. It is identical to human insulin naturally produced by the body.
Insulin is a hormone normally produced in the human body by the pancreas. It plays a role in the metabolism of carbohydrates, fats, and proteins, including lowering blood glucose (sugar) levels.
Diabetes is caused by the pancreas being unable to produce insulin in amounts sufficient to control blood glucose levels.
Polhumin MIX-2 is an intermediate-acting insulin. This means that the onset of action, consisting of lowering blood glucose levels, occurs approximately 30 minutes after injection, the peak effect occurs between 2 and 8 hours, and the total duration of action lasts up to 24 hours.
The medicine is available in a 3 ml cartridge intended for use with an injection device.
Warning! Do not introduce any other products into insulin cartridges. Insulins must not be mixed with other medicines in the same syringe.

2. Important information before using Polhumin Mix-2

When not to use Polhumin Mix-2

if the patient is allergic to this insulin or any of the other ingredients of this medicine (listed in section 6).
if the patient is experiencing symptoms indicating an approaching hypoglycaemic state (low blood sugar).

Warnings and precautions

If current treatment provides good diabetes control, warning symptoms of excessive reduction in glucose concentration (hypoglycaemia – see below) in the blood may not be noticeable. It is essential to carefully plan meal times, frequency and level of physical activity. Blood glucose levels should also be monitored frequently by regular testing.
Some individuals who experienced hypoglycaemia (low blood glucose) after switching from animal to human insulin have reported that warning symptoms of hypoglycaemia were less pronounced or completely different than before. If hypoglycaemia occurs frequently or if there are difficulties recognizing its warning symptoms, consult a doctor.
Insulin requirements may also change after alcohol consumption.
If the patient plans to travel abroad, they should inform their doctor. Differences in time zones may require adjustments in the timing of injections and meals.
If the patient has been diagnosed with kidney or liver disease, they should inform their doctor. The doctor will adjust the insulin dose accordingly. It should be remembered that in many medical conditions (e.g. liver, kidney, adrenal or pituitary disorders, colds) and stressful situations, significant fluctuations in blood glucose levels may occur, potentially leading to complications of insulin therapy: hypoglycaemia (low blood sugar) or hyperglycaemia (high blood sugar).

Polhumin Mix-2 in cartridges is intended exclusively for subcutaneous injection using a reusable injection pen. If insulin must be administered by another method, consult a doctor.
Skin changes at the injection site
Injection sites should be rotated to prevent the development of skin changes, such as lumps under the skin. Insulin injected into an area with lumps may not work properly (see "How to use Polhumin Mix-2"). If insulin is currently being injected into an area with lumps, contact a doctor before changing the site.
The doctor may recommend more frequent blood glucose monitoring and adjustment of insulin or other antidiabetic medication doses.

Hypoglycaemia (low blood sugar) may result from administering too high a dose of insulin, delayed or missed meals, reduced carbohydrate intake, increased physical activity, or accelerated insulin absorption (e.g. due to elevated skin temperature during sunbathing or bathing in hot water). Symptoms of hypoglycaemia include: excessive sweating, weakness, hunger, palpitations, cold sensation, anxiety, hand tremors, blurred vision, headache, and in severe cases – disorientation, seizures, or loss of consciousness. Warning! In case of recurrent hypoglycaemia, contact a doctor to determine the cause of low blood sugar and possibly adjust insulin dosage. Do not administer fluids or food orally to an unconscious person due to the risk of choking. Place the unconscious person in the recovery position and seek immediate medical help. If severe hypoglycaemia is not treated promptly, it may lead to temporary or permanent brain damage or death.
Hyperglycaemia. Abnormally high blood glucose levels during insulin therapy are most commonly caused by: failure to follow a diabetic diet, inadequate insulin therapy (too low insulin dose), increased insulin requirements (due to infections, surgery, trauma), lifestyle changes (reduced physical activity), or concomitant use of other medications, e.g. oral contraceptives, glucocorticosteroids, or thiazide diuretics. Symptoms of hyperglycaemia include: excessive thirst, loss of appetite, frequent urination of large volumes, fatigue, drowsiness, dry skin and mucous membranes. Prolonged hyperglycaemia may lead to ketoacidosis (acetone breath odour, rapid and deep breathing, presence of ketones in urine) or coma. The appearance of the above symptoms requires immediate medical intervention.

To avoid hypoglycaemia or hyperglycaemia:

Always carry a spare injection pen and cartridge of Polhumin Mix-2 insulin.
Always carry identification indicating that you have diabetes.
Always carry sugar cubes.

Children
The doctor will recommend an appropriate dosage to achieve normal blood glucose levels (normoglycaemia), according to physiological needs.
Polhumin Mix-2 and other medicines
Inform your doctor about all medicines currently or recently taken, as well as any medicines you plan to take.
It is essential to inform any doctor treating you for reasons other than diabetes that you are using insulin.
The body's insulin requirements may change when taking the following concomitant medications:

Medicines that reduce insulin action:

estrogens (including oral contraceptives, hormone replacement therapy),
thyroid hormones,
lithium compounds (used in the treatment of certain psychiatric disorders),
danazol (used, among others, in the treatment of benign breast disorders (fibrocystic breast disease), endometriosis (endometrial tissue growth outside the uterine cavity)),
sympathomimetic agents (e.g. epinephrine, terbutaline used in asthma treatment),
nicotinic acid,
steroids (used in inflammatory conditions),
phenytoin (an anticonvulsant)

Medicines that enhance insulin action:

β-adrenergic blocking agents (used in the treatment of heart diseases, hypertension – e.g. propranolol),
certain antidepressants (e.g. monoamine oxidase inhibitors such as iproniazid),
salicylates (e.g. aspirin),
somatostatin analogues (e.g. octreotide),
ethyl alcohol. Oral antidiabetic drugs reduce insulin requirements. Warning! Do not mix other medicines with insulin in the cartridge. Insulin must not be administered in the same syringe with other medicines.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult a doctor or pharmacist before using this medicine.
In women of childbearing age with diabetes, it is essential to achieve and maintain normal blood glucose levels during insulin therapy.
Insulin does not cross the placenta into fetal blood.
Insulin requirements decrease during the first trimester of pregnancy but increase during the second and third trimesters. In the final stage of pregnancy, insulin requirements are approximately twice as high compared to pre-pregnancy levels.
Insulin requirements decrease at the onset of labour and after delivery (insulin dose approaches that used in non-pregnant diabetic women).
Insulin does not pass into human milk. Patients treated with insulin may breastfeed. Insulin dosage or diet adjustments are often necessary.
Driving and operating machinery
Be aware of possible hypoglycaemic symptoms. The ability to concentrate and react is usually impaired during hypoglycaemia. Never drive if symptoms suggest an approaching hypoglycaemic state. Consult your doctor to carefully evaluate your ability to drive or operate machinery if you experience frequent hypoglycaemic episodes or have difficulty recognizing their symptoms.
Polhumin Mix-2 contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose unit, meaning the medicine is considered "sodium-free".

3. How to use Polhumin Mix-2

This medicine should always be used exactly as prescribed by your doctor. If in doubt, consult your
doctor.
Insulin dosage is individual for each patient. The insulin dose is determined based on the patient's
age, physical activity, health status (e.g. presence of kidney failure), and concomitant use of other
medicines. The exact insulin dose should be established through regular monitoring of blood and
urine glucose levels.
Whenever changing insulin—e.g., from mixed (porcine-bovine) or bovine insulin to human insulin,
changing formulation, or changing manufacturer—dose adjustment may be necessary and must be
carried out under medical supervision.
In patients who are adequately controlled with highly purified porcine insulin or other highly purified
human insulins, no other dosage changes than routine adjustments aimed at maintaining stable
control of the patient's condition are anticipated.
It is essential to strictly adhere to the follow-up appointments recommended by the doctor.
Regular monitoring of blood or urine glucose levels is required during treatment.
Polhumin Mix-2 in a pre-filled injector is intended exclusively for subcutaneous injection. If
administration by another route is necessary, consult your doctor.
Subcutaneous injections should be administered in the abdominal area, buttocks, thigh, or upper
arm. Injection sites should be rotated to avoid lipodystrophy (thickening of the skin).

Preparing the insulin cartridge
Before inserting the insulin cartridge into the insulin delivery device, the cartridge should be gently
rotated up and down several times so that the glass bead can move freely from one end to the
other. This procedure should be repeated several times (approximately 10 times) until a uniform
cloudy or milky suspension is obtained. If the cartridge is already inserted in the injector, rotate the
device several times as described above.
These steps must be performed before each insulin injection.

Administering the injection

Pinch the skin between two fingers, insert the needle at an angle of approximately 45° into the skin fold, and inject insulin subcutaneously;
Withdraw the needle and gently press on the injection site for several seconds to prevent insulin leakage. Injection sites should be rotated as advised by your doctor. Do not reuse used needles. Needles must be disposed of safely. Do not share needles or injectors with other people. The cartridge may be used until its contents are exhausted, after which it must be safely discarded. If you feel the medicine's effect is too strong or too weak, consult your doctor.

Use of a higher than recommended dose of Polhumin Mix-2
If a higher than recommended dose is taken, consult your doctor immediately.
Insulin overdose may lead to hypoglycemia (causes and symptoms of hypoglycemia—see section 2
"Important information before using Polhumin Mix-2").
Management of insulin overdose depends on the severity of hypoglycemia:

In cases of mild to moderate hypoglycemia, immediately consume 2–5 sugar cubes or teaspoons of sugar dissolved in water, or a glass of sugary drink. Do not administer insulin if symptoms suggest possible hypoglycemia. Always carry sugar, sweets, biscuits, or fruit juice with you;
In severe hypoglycemia, when the patient loses consciousness, a trained person should administer glucagon. As soon as consciousness is regained, consume sugar or a carbohydrate-containing snack. If the patient does not regain consciousness after glucagon administration, immediate hospital treatment is required. After each glucagon administration, seek medical advice to determine the cause of hypoglycemia and prevent future episodes. Inform family members, friends, and coworkers that in case of unconsciousness, the person should be placed in the recovery position and immediate medical assistance sought. Food or drink must not be given to an unconscious person due to the risk of choking. In cases of hypoglycemia with loss of consciousness or frequent hypoglycemic episodes, contact your treating physician, as adjustment of insulin dose, timing of administration, diet, and physical activity may be necessary.

Missed dose of Polhumin Mix-2
If a dose of insulin is missed, contact your doctor.
Missing a dose may result in hyperglycemia.
Do not use a double dose to make up for a missed dose.
If a dose is missed at a fixed, scheduled time, the missed dose should be administered as soon as possible, provided sufficient time remains before the next scheduled dose. Otherwise, administer the next dose at the usual time and continue regular dosing.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
As with other insulins, hypoglycaemia is the most commonly occurring complication of insulin therapy.

Adverse reactions reported commonly (in less than 1 in 10 patients):
Local allergic reaction – symptoms at the injection site (redness, swelling, itching, pain, and bruising at the injection site) may occur during insulin treatment. Most of these symptoms are usually transient and resolve during continued treatment.

Skin changes at the injection site
If insulin is injected too frequently into the same site, fatty tissue may shrink (lipoatrophy) or thicken (lipohypertrophy) (uncommon – no more frequently than in 1 in 100 patients). Lumps under the skin may also be caused by accumulation of a protein called amyloid (cutaneous amyloidosis, frequency unknown). Insulin injected into an area where lumps are present may not work properly. Injection sites should be rotated each time – this will help prevent these skin changes.

Adverse reactions reported very rarely (in less than 1 in 10,000 patients):
Generalized allergic reaction – may manifest as generalized skin rash, itching, sweating, gastrointestinal disturbances, angioedema, breathing difficulties, palpitations, drop in blood pressure, and fainting/loss of consciousness.
➢ If any of these symptoms occur while using Polhumin MIX-2, contact your doctor immediately.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring of 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 reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions enables better assessment of the safety profile of the medicine.

5. How to store Polhumin MIX-2

Keep out of sight and reach of children.
Store in a refrigerator (2°C – 8°C).
Do not freeze.
Keep in the original packaging to protect from light.
After first opening, store the container below 25°C and use within 28 days.
Do not use this medicinal product after the expiry date stated on the packaging. The expiry date refers to the last day of the month indicated.
Do not use this medicinal product if you notice any changes in the appearance of the contents.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the package and other information

What Polhumin Mix-2 contains
The active substance is biosynthetic highly purified human insulin.
1 ml of suspension contains 100 IU of human insulin.
One cartridge contains 3 ml of suspension, equivalent to 300 IU of biphasic insulin
in the proportion of 2 parts soluble insulin and 8 parts isophane insulin.
Other ingredients of the medicine are protamine sulfate, disodium phosphate dodecahydrate, phenol, metacresol,
glycerol, zinc chloride (4% Zn solution), hydrochloric acid (0.1 mol/l solution), sodium hydroxide
(0.1 mol/l solution), and water for injections.

What Polhumin Mix-2 looks like and contents of the pack
White or almost white, neutral, sterile, aqueous suspension of human insulin in a cartridge at pH 6.9–7.8.

Packaging
5 cartridges of 3 ml each in a PVC/Al blister pack in a cardboard box.
The cartridges are colorless neutral glass cylinders, internally siliconized, sealed with a rubber stopper and an aluminum cap with a rubber disc made of bromobutyl mixture. Each cartridge contains 2 glass beads.

Marketing Authorisation Holder and Manufacturer
Tarchomin Pharmaceutical Works "Polfa" Joint Stock Company
A. Fleminga 2 Street
03-176 Warsaw
Phone number: 22 811-18-14
For further information, please contact the representative of the Marketing Authorisation Holder.