Polhumin mix-3

Package leaflet: Information for the user

Polhumin MIX-3, 100 IU/ml, injection suspension
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 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 reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Leaflet contents:

1. What Polhumin MIX-3 is and what it is used for
2. Important information before using Polhumin MIX-3
3. How to use Polhumin MIX-3
4. Possible side effects
5. How to store Polhumin MIX-3
6. Contents of the pack and other information

1. What Polhumin MIX-3 is and what it is used for

Polhumin MIX-3 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 insulin naturally produced by the human 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' inability to produce insulin in amounts sufficient to control blood glucose levels.
Polhumin MIX-3 is an intermediate-acting insulin. This means that the onset of action, consisting of a reduction in 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 pen.
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-3

When not to use Polhumin Mix-3

• 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 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) may not be noticeable. It is important to carefully plan meal times, frequency and level of physical activity. Blood glucose levels should also be monitored frequently by testing blood glucose concentration.

• 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 in recognizing its warning signs, consult a physician.

• Insulin requirements may also change after consuming alcohol.

• If the patient plans to travel abroad, they should inform their doctor. Time zone differences may require adjusting the timing of injections and meals.

• 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 gland disorders, colds) and during stressful situations, significant fluctuations in blood glucose levels may occur, potentially leading to complications of insulin therapy: hypoglycaemia (reduced blood glucose) or hyperglycaemia (elevated blood glucose).

Polhumin Mix-3 in cartridges is intended exclusively for subcutaneous injection using a reusable injection pen. If insulin must be administered by another method, consult a physician.
Skin changes at the injection site
Injection sites should be rotated to prevent 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-3"). If insulin is currently being injected into an area with lumps, contact a physician before changing the site.
The physician may recommend more frequent blood glucose monitoring and adjustment of the insulin dose or other antidiabetic medications.

• Hypoglycaemia (low blood sugar) may result from administering too high an insulin dose, delayed or missed meals, meals with reduced carbohydrate content, increased physical activity, or accelerated insulin absorption (e.g. due to elevated skin temperature during sunbathing or bathing in hot water). Hypoglycaemia symptoms include: excessive sweating, weakness, hunger, palpitations, feeling cold, anxiety, hand tremors, blurred vision, headache, and in more severe cases - disorientation, seizures, loss of consciousness. Caution! In case of recurrent hypoglycaemia, contact a physician to determine the cause of low blood sugar and possibly adjust the insulin dosage. Never administer fluids or food orally to an unconscious person due to the risk of choking. An unconscious person should be placed in the recovery position and a physician should be summoned immediately. If severe hypoglycaemia is not treated promptly, it may lead to temporary or permanent brain damage or death.
• Hyperglycaemia. Abnormally elevated blood glucose levels occurring during insulin therapy are most commonly caused by: failure to follow a diabetic diet, inadequate insulin therapy (insufficient 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 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 ketone bodies in urine) or coma. The presence of any of the above symptoms requires immediate medical attention.

To avoid hypoglycaemia or hyperglycaemia:

• Always carry a spare injection pen and a cartridge of Polhumin Mix-3 insulin.
• Always carry identification indicating that you have diabetes.
• Always carry sugar cubes.

Children
The physician will recommend an appropriate dosage to achieve normal blood glucose levels (normoglycaemia), according to physiological needs.

Polhumin Mix-3 and other medicines
Inform your physician about all medicines currently or recently taken, as well as any medicines you plan to take.
It is essential to inform any physician 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:

• oestrogens (including oral contraceptives, hormone replacement therapy),
• thyroid hormones,
• lithium compounds (used in treating certain psychiatric disorders),
• danazol (used, among others, for 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 blockers (used in treating 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. Caution! 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 physician 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 final stage of pregnancy, insulin requirements are approximately twice as high compared to the pre-pregnancy period.
Insulin requirements decrease at the onset of labour and after delivery (the 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 impending hypoglycaemia. Consult a physician to carefully evaluate the ability to drive or operate machinery if frequent hypoglycaemic episodes occur or if there are difficulties recognizing symptoms.

Polhumin Mix-3 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-3

This medicine should always be used exactly as prescribed by the doctor. In case of 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), as well as concomitant use of
other medicines. The exact insulin dose should be established through regular monitoring of blood
and urine glucose levels.
Whenever changing insulin, for example from mixed (porcine-bovine) or bovine insulin to human
insulin, or changing the formulation or even the manufacturer, a dosage adjustment may be
necessary and should be carried out under medical supervision.
In patients for whom highly purified porcine insulin or other highly purified human insulins provide
adequate glucose control, no dosage changes other than routine adjustments aimed at maintaining
consistent patient monitoring 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-3 in a prefilled cartridge 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 rotated
upside down and right side up 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.

Administering the injection

• Grasp 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 the injection site for several seconds to prevent insulin leakage. Injection sites should be rotated as recommended by the doctor. Do not reuse used needles. Needles should be disposed of safely. Do not share needles or insulin pens with other people. The cartridge may be used until its contents are exhausted, after which it should be safely disposed of. If you feel that the medicine's effect is too strong or too weak, consult your doctor.

Use of a higher than recommended dose of Polhumin Mix-3
If more than the prescribed dose has been 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-3").
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, the patient should consume sugar or a sugary snack. If the patient does not regain consciousness after glucagon administration, immediate hospital treatment is required. After each glucagon administration, medical advice should be sought to determine the cause of hypoglycemia 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 sought. Food and drink must not be given to an unconscious person due to the risk of aspiration. 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.

Missing a dose of Polhumin Mix-3
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 medicine should be administered as soon as
possible, provided there is sufficient time before the next scheduled dose, or the next dose should
be administered at the usual time, continuing regular dosing.

4. Possible adverse reactions

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

Adverse reactions reported as common (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 diminish during the course of treatment.

Skin changes at the injection site
If insulin is injected too frequently into the same spot, 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 with such lumps may not work properly. The injection site should be changed each time – this will help prevent these skin changes.

Adverse reactions reported as very rare (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 during treatment with Polhumin Mix-3, 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 at 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 helps provide more information on the safety of the medicine.

5. How to store Polhumin MIX-3

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 container 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 a change in the appearance of the contents is observed.
Medicinal products should 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-3 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 a ratio of 3 parts soluble insulin and 7 parts isophane insulin.
Other ingredients 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-3 looks like and contents of the pack
White or almost white, neutral, sterile, aqueous suspension of human insulin in a cartridge, 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, closed at both ends
with a rubber plunger and an aluminum cap with a rubber disc made of a bromobutyl rubber 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 more detailed information, please contact the representative of the Marketing Authorisation Holder.