Package leaflet: Information for the patient

Polhumin MIX-4, 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, please ask your doctor or pharmacist.
This medicine has been prescribed for you personally. Do not pass it on to others. It may harm them even if their symptoms are the same as yours.
If you experience any side effects, including any not listed in this leaflet, please inform your doctor or pharmacist. See section 4.

Leaflet contents:

What Polhumin MIX-4 is and what it is used for
What you need to know before using Polhumin MIX-4
How to use Polhumin MIX-4
Possible side effects
How to store Polhumin MIX-4
Contents of the pack and other information

1. What Polhumin MIX-4 is and what it is used for

Polhumin MIX-4 is human insulin used in the treatment of diabetes. This insulin is produced using recombinant DNA technology in Escherichia coli bacteria. It is identical to human insulin naturally produced by the human body.
Insulin is a hormone normally produced in the human body by the pancreas. It plays a key 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 sufficient insulin to maintain normal blood glucose levels.
Polhumin MIX-4 is an intermediate-acting insulin. This means that its onset of action, which involves lowering blood glucose levels, occurs approximately 30 minutes after injection, peak action 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 pen.
Warning! Do not mix any other products into insulin cartridges. Insulin must not be mixed with other medicines in the same syringe.

2. Important information before using Polhumin Mix-4

When not to use Polhumin Mix-4

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

Warnings and precautions

If the current treatment provides good diabetes control, warning symptoms of excessive reduction in glucose concentration (hypoglycemia – see below) in the blood may not be noticeable. It is important to carefully plan meal times, frequency of physical activity,

and overall activity level. Blood glucose levels should also be monitored frequently by testing
blood glucose concentration.

Some individuals who experienced hypoglycemia (low blood glucose) after switching from animal to human insulin have reported that warning symptoms of hypoglycemia were less pronounced or completely different than before. If hypoglycemia occurs frequently or if there are difficulties recognizing its warning signs, consult a physician.
Insulin requirements may also change after alcohol consumption.
If the patient plans to travel abroad, they should inform their doctor. Time zone differences may require injections and meals to be taken at different times.
If the patient has 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 during stressful situations, significant fluctuations in blood glucose levels may occur, which can lead to complications of insulin therapy: hypoglycemia (low blood sugar) or hyperglycemia (high blood sugar).

Polhumin Mix-4 in cartridges is intended exclusively for subcutaneous injection
using a reusable insulin pen. If insulin must be administered by another method, consult a doctor.
Skin changes at the injection site
The injection site should be rotated to prevent the development of skin changes, such as lumps under
the skin surface. Insulin injected into an area with lumps may not work properly (see "How to use Polhumin Mix-4"). If insulin is currently being injected into an area with lumps, contact a doctor before changing the site.
The doctor may recommend more frequent monitoring of blood glucose levels and adjustment of the
insulin dose or other antidiabetic medications.

Hypoglycemia (low blood sugar) may result from administering too high an insulin dose, delaying or skipping a meal, reduced carbohydrate intake, increased physical activity, or increased insulin absorption rate (e.g. due to elevated skin temperature during sunbathing or bathing in hot water). Symptoms of hypoglycemia include excessive sweating, weakness, hunger, palpitations, feeling cold, anxiety, hand tremors, visual disturbances, headache, and in more severe cases – disorientation, seizures, or loss of consciousness. Warning! In case of recurrent hypoglycemia, contact a doctor to determine the cause of low blood sugar and possibly adjust the insulin dose. Do not give oral fluids or food to an unconscious person due to risk of choking. An unconscious person should be placed in the recovery position and a doctor should be called immediately. If severe hypoglycemia is not treated promptly, it may cause temporary or permanent brain damage or death.
Hyperglycemia. Abnormally high blood glucose levels occurring during insulin therapy are most commonly due to: failure to follow a diabetic diet, inadequate insulin therapy (too low insulin dose), increased insulin requirements (due to infections, surgery, trauma), changes in lifestyle (reduced physical activity), or concomitant use of other medications, e.g. oral contraceptives, glucocorticosteroids, or thiazide diuretics. Symptoms of hyperglycemia include excessive thirst, loss of appetite, frequent urination of large volumes, fatigue, drowsiness, dry skin and mucous membranes. Prolonged hyperglycemia may lead to ketoacidosis (acetone breath odor, rapid and deep breathing, presence of ketone bodies in urine) or coma. The presence of the above symptoms requires immediate medical intervention.

To avoid hypoglycemia or hyperglycemia:

Always carry a spare insulin pen and cartridge of Polhumin Mix-4.
Always carry identification indicating that you have diabetes.
Always carry sugar cubes.

Children
The doctor will recommend an appropriate dose to achieve normal blood glucose levels (normoglycemia), in accordance with physiological needs.
Polhumin Mix-4 and other medicines
Inform your doctor about all medicines you are currently taking or have 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 medicines concurrently:
Medicines that reduce insulin action:

estrogens (including oral contraceptives, hormone replacement therapy),
thyroid hormones,
lithium compounds (used in treating certain psychiatric disorders),
danazol (used in treating, among others, benign breast disorders (fibrocystic breast disease), endometriosis),
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 treating heart diseases and hypertension – e.g. propranolol),
certain antidepressants (e.g. monoamine oxidase inhibitors such as iproniazid),
salicylates (e.g. aspirin),
somatostatin analogs (e.g. octreotide),
ethyl alcohol. Oral antidiabetic drugs reduce insulin requirements. Warning! Do not mix other medicines into insulin cartridges. Insulin must not be administered together with other medicines in the same syringe.

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 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 late stages of pregnancy, insulin requirements are approximately twice as high compared to pre-pregnancy levels.
Insulin requirements decrease at the onset of labor 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 dose or diet adjustments are often necessary.
Driving and operating machinery
Be aware of possible hypoglycemia symptoms. Ability to concentrate and react is usually impaired during hypoglycemia. Never drive if symptoms suggest impending hypoglycemia. Consult your doctor to carefully evaluate your ability to drive or operate machinery if you experience frequent hypoglycemic episodes or have difficulty recognizing hypoglycemia symptoms.
Polhumin Mix-4 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-4

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 types—for example, from mixed (porcine-bovine) or bovine insulin to
human insulin—or changing formulations, including changing manufacturers, a dose adjustment may
be necessary and should be carried out under medical supervision.
In patients who are adequately controlled with highly purified porcine insulin or other highly
purified human insulins, no changes in dosing other than routine adjustments aimed at maintaining
consistent patient control 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-4 in a pre-filled pen is intended exclusively for subcutaneous injection. If insulin
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 lipohypertrophy.
Preparing the insulin in cartridges
Before inserting the insulin cartridge into the insulin delivery pen, the cartridge should be gently
rotated upside down and back 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 in the pen, rotate the pen as
described above.
These steps should be performed before each insulin injection.
Performing the injection

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

Use of a higher than recommended dose of Polhumin Mix-4
If more than the recommended dose has been taken, seek medical advice immediately.
Insulin overdose may lead to hypoglycaemia (causes and symptoms of hypoglycaemia—see section 2
"Important information before using Polhumin Mix-4").
Management of insulin overdose depends on the severity of hypoglycaemia:

In cases of mild to moderate hypoglycaemia, 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 hypoglycaemia. Always carry sugar, sweets, biscuits, or fruit juice.
In severe hypoglycaemia, when the patient loses consciousness, a trained person should administer glucagon. As soon as consciousness is regained, the patient should consume sugar or a sugary snack. If the patient does not regain consciousness after glucagon administration, they must be treated in a hospital. After each glucagon administration, medical advice should be sought to determine the cause of hypoglycaemia and to 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 should be obtained. Food or drink must not be given to an unconscious person due to the risk of choking. In cases of hypoglycaemia with loss of consciousness or frequent hypoglycaemic episodes, contact your treating physician, as a change in insulin dose, timing of administration, diet, or physical activity may be necessary.

Missed dose of Polhumin Mix-4
If a dose of insulin is missed, contact your doctor.
If a dose is missed, hyperglycaemia may occur.
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 there is sufficient time 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 experiences 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 – not more frequently than in 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 such lumps may not work properly. The injection site should be rotated each time – this helps prevent these skin changes.

Adverse reactions reported very rarely (in less than 1 in 10,000 patients):
Generalised hypersensitivity 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 such symptoms occur while using Polhumin MIX-4, contact your doctor immediately.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: +48 22 4921301
Fax: +48 22 4921309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Polhumin MIX-4

Keep out of the sight and reach of children.
Store in a refrigerator (2°C – 8°C).
Do not freeze.
Store in the original packaging to protect from light.
After first opening, store the contents at a temperature 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 stated month.
Do not use this medicinal product if any change in the appearance of the contents is observed.
Medicinal products must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What Polhumin Mix-4 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 proportions of 4 parts soluble insulin and 6 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-4 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 in PVC/Aluminum blisters, in a cardboard box.
The cartridges are colorless glass cylinders made of neutral glass, internally siliconized,
double-crimped with a rubber stopper and an aluminum cap with a rubber disc
made from a bromobutyl rubber mixture. Each cartridge contains 2 glass beads.
Marketing authorization holder and manufacturer
Tarchomin Pharmaceutical Works "Polfa" Joint Stock Company
A. Fleminga 2 Street
03-176 Warsaw
Phone number: 22 811-18-14
For more detailed information, please contact the representative of the Marketing Authorization Holder.