Polhumin mix-5

Package leaflet: Information for the user

Polhumin MIX-5, 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. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet contents:

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

1. What Polhumin MIX-5 is and what it is used for

Polhumin MIX-5 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 produced by the human body.
Insulin is a hormone naturally produced in the human body by the pancreas. It plays a role in the metabolism of carbohydrates, fats, and proteins, among others by 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-5 is an intermediate-acting insulin. This means that the onset of action, consisting of 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 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-5

When not to use Polhumin Mix-5

• 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 approaching hypoglycaemic state (low blood sugar level).

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 important to carefully plan meal times, frequency of physical activity,
  and overall activity level. Blood glucose levels should also be monitored frequently by regular testing
  of blood glucose concentration.

• Some individuals who experienced hypoglycaemia (low blood glucose concentration) 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 symptoms, consult a doctor.

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

Polhumin Mix-5 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 surface. Insulin injected into an area with lumps may not work properly (see "How to use Polhumin Mix-5"). 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.

• Hypoglycaemia (low blood sugar) may result from administering too high a dose of insulin, delayed or missed meals, reduced carbohydrate intake in meals, increased physical activity, or increased insulin absorption rate (e.g. due to elevated skin temperature during sunbathing or bathing in hot water). Symptoms of hypoglycaemia include: excessive sweating, weakness, hunger, palpitations, feeling cold, anxiety, hand tremors, visual disturbances, headache, and in more severe cases – disorientation, seizures, 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 unconscious individuals due to the risk of choking. An unconscious person should be placed in the recovery position and a doctor should be called 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 of urine, 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 the above-mentioned symptoms requires immediate medical intervention.

To avoid hypoglycaemia or hyperglycaemia:

• Always carry a spare injection pen and a cartridge of Polhumin Mix-5 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-5 and other medicines
Inform your doctor about all medicines currently taken or recently used, as well as any medicines you plan to take.
It is essential to inform any doctor treating you for conditions other than diabetes that you are using insulin.
The body's insulin requirements may change when taking the following medicines simultaneously:
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 diseases (fibrocystic breast disease), endometriosis (growth of uterine lining 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 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 into insulin cartridges. 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 with diabetes of childbearing age, 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 following two 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 (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 a doctor to carefully assess the ability to drive or operate machinery if frequent hypoglycaemic episodes occur or if there are difficulties in recognizing hypoglycaemia symptoms.
Polhumin Mix-5 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-5

This medicine should always be used as directed by the physician. 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 medications. The exact insulin dose should be established through regular monitoring of blood and urine glucose levels.

Each time changing insulin—e.g., from mixed (porcine-bovine) or bovine insulin to human insulin, or changing formulation or manufacturer—dose adjustments may be necessary and must 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 other dosage changes beyond routine adjustments aimed at maintaining consistent patient monitoring are anticipated.

It is essential to strictly adhere to the schedule of follow-up visits recommended by the physician.
Regular monitoring of blood or urine glucose levels is required during treatment.

Polhumin MIX-5 in prefilled cartridges 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-containing cartridge into the insulin delivery device, rotate the cartridge several times upside down and upright, allowing the glass bead to move freely from one end to the other. Repeat this action approximately 10 times until a uniform cloudy or milky suspension is obtained. If the cartridge is already in the insulin delivery device, rotate the device 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 according to the physician’s instructions. Do not reuse used needles. Needles must be disposed of safely. Do not share needles or insulin delivery devices with others. A 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-5
If more medicine is taken than recommended, seek immediate medical advice.
Insulin overdose may lead to hypoglycemia (causes and symptoms of hypoglycemia—see section 2 “Important information before using Polhumin MIX-5”).

Management of insulin overdose depends on the severity of hypoglycemia:

• In 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;
• In severe hypoglycemia, when the patient loses consciousness, a trained person should administer glucagon. As soon as consciousness is regained, 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 must be obtained 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 sought. Food or 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 the treating physician, as adjustment of insulin dose, timing of administration, diet, and physical activity may be necessary.

Missed dose of Polhumin MIX-5
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 its usual scheduled time, administer the missed dose as soon as possible, provided sufficient time remains before the next scheduled dose. Otherwise, take 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 common complication associated with 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 areas 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):
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-5, contact a doctor immediately.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform a doctor, pharmacist, or nurse. Adverse reactions 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 4921 301
Fax: +48 22 4921 309
Website: https://smz.ezdrowie.gov.pl

Adverse reactions can also be reported to the Marketing Authorisation Holder.
Reporting adverse reactions enables better monitoring of the medicine’s safety.

5. How to store Polhumin MIX-5

Keep out of the sight and reach of children.
Store in a refrigerator (2ºC – 8ºC).
Do not freeze.
Store in the original packaging to protect from light.
After first opening, store the container at a temperature not exceeding 25ºC for a maximum of 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 you notice any change 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 pack and other information

What Polhumin Mix-5 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 5 parts soluble insulin to 5 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-5 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/Aluminum blister pack, in a cardboard box.
The cartridges are colorless glass cylinders made of neutral glass, internally siliconized,
sealed with a rubber stopper and an aluminum cap with a rubber disc made of a 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 more detailed information, please contact the representative of the Marketing Authorisation Holder.