Protaphane^® HM Penfill (Suspension) Instructions for Use

Marketing Authorization Holder

Novo Nordisk A/S (Denmark)

ATC Code

A10AC01 (Human insulin)

Active Substance

Human insulin isophane rDNA origin

Human insulin isophane rDNA origin (USP Pharmacopoeia)

Dosage Form

Protaphane® HM Penfill®

Suspension for subcutaneous administration 100 IU/1 ml: 3 ml cartridges 5 pcs.

Dosage Form, Packaging, and Composition

Suspension for subcutaneous administration is white in color, separates upon standing, forming a white sediment and a colorless or almost colorless supernatant; upon mixing, the sediment should resuspend.

Excipients: zinc chloride – 33 mcg, glycerol – 16 mg, metacresol – 1.5 mg, phenol – 0.65 mg, disodium hydrogen phosphate dihydrate – 2.4 mg, protamine sulfate – about 0.35 mg, sodium hydroxide – about 0.4 mg and/or hydrochloric acid – about 1.7 mg (for pH adjustment), water for injection – up to 1 ml.

3 ml – cartridges made of colorless glass (5) – blister packs (1) – cardboard packages.

* 1 IU corresponds to 35 mcg of anhydrous human insulin.

Clinical-Pharmacological Group

Intermediate-acting human insulin

Pharmacotherapeutic Group

Intermediate-acting insulin

Pharmacological Action

Intermediate-acting human insulin produced using recombinant DNA technology. It interacts with a specific receptor on the outer cytoplasmic membrane of cells and forms an insulin-receptor complex that stimulates intracellular processes, including the synthesis of a number of key enzymes (hexokinase, pyruvate kinase, glycogen synthase). The decrease in blood glucose levels is due to increased intracellular transport, enhanced uptake and utilization by tissues, stimulation of lipogenesis, glycogenesis, and a decrease in the rate of glucose production by the liver.

The duration of action of insulin preparations is mainly determined by the rate of absorption, which depends on several factors (e.g., dose, method and site of administration), which is why the action profile of insulin is subject to significant variations, both among different people and in the same person.

On average, after subcutaneous administration, this insulin begins to act within 1.5 hours, the maximum effect develops between 4 and 12 hours, and the duration of action is up to 24 hours.

Pharmacokinetics

The completeness of absorption and the onset of insulin effect depend on the injection site (abdomen, thigh, buttocks), dose, and insulin concentration in the preparation.

It is distributed unevenly in tissues; does not cross the placental barrier or into breast milk. It is metabolized in the liver and kidneys by the enzyme insulinase. It is excreted by the kidneys (30-80%).

Indications

Type 1 diabetes mellitus; Type 2 diabetes mellitus: stage of resistance to oral hypoglycemic agents, partial resistance to these drugs (during combination therapy), intercurrent illnesses; Type 2 diabetes mellitus in pregnancy.

ICD codes

Dosage Regimen

Administer subcutaneously only.

Determine the dose individually for each patient based on blood glucose levels.

The typical daily dosage range is 0.5 to 1 IU per kg of body weight.

Adjust the dose according to the patient’s metabolic needs, physical activity level, and diet.

Inject once or twice daily as directed by a physician.

Rotate injection sites within the same anatomical region (abdomen, thigh, buttock) to prevent lipodystrophy.

Always administer at the same time(s) each day to maintain stable glycemic control.

Shake the cartridge thoroughly until the suspension appears uniformly white and cloudy.

Do not use the product if it remains clear after mixing or if particles are visible.

Use only with compatible Novo Nordisk insulin delivery devices (pen injectors).

Monitor blood glucose regularly, especially during dose adjustments, illness, or changes in routine.

Increase vigilance for hypoglycemia when initiating therapy, increasing the dose, or switching from other insulins.

Adverse Reactions

Side effects due to the effect on carbohydrate metabolism: hypoglycemic conditions (pallor of the skin, increased sweating, palpitations, tremor, hunger, agitation, paresthesia of the oral mucosa, headache, dizziness, decreased visual acuity). Severe hypoglycemia can lead to the development of hypoglycemic coma.

Allergic reactions: skin rash, angioedema, anaphylactic shock.

Local reactions: hyperemia, swelling and itching at the injection site, with prolonged use – lipodystrophy at the injection site.

Other: edema, transient decrease in visual acuity (usually at the beginning of therapy).

Contraindications

Hypersensitivity to insulin; hypoglycemia.

Use in Pregnancy and Lactation

There are no restrictions on the treatment of diabetes mellitus with insulin during pregnancy, since insulin does not cross the placental barrier. When planning pregnancy and during it, it is necessary to intensify the treatment of diabetes mellitus. The need for insulin usually decreases in the first trimester of pregnancy and gradually increases in the second and third trimesters.

During childbirth and immediately after it, the need for insulin may decrease sharply. Soon after childbirth, the need for insulin quickly returns to the level that was before pregnancy.

Use in Hepatic Impairment

Should be used with caution in patients with impaired liver function. Dose adjustment is necessary.

Use in Renal Impairment

Should be used with caution in patients with impaired renal function. Dose adjustment is necessary.

Geriatric Use

Should be prescribed with caution to elderly patients. Dose adjustment is necessary.

Special Precautions

During insulin therapy, constant monitoring of blood glucose concentration is necessary.

Causes of hypoglycemia, in addition to insulin overdose, may include: changing the drug, skipping a meal, vomiting, diarrhea, increased physical activity, diseases that reduce the need for insulin (impaired liver and kidney function, hypofunction of the adrenal cortex, pituitary gland or thyroid gland), changing the injection site, as well as interaction with other drugs.

Incorrect dosing or interruptions in insulin administration, especially in patients with type 1 diabetes mellitus, can lead to hyperglycemia. Usually, the first symptoms of hyperglycemia develop gradually over several hours or days. They include the appearance of thirst, frequent urination, nausea, vomiting, dizziness, redness and dryness of the skin, dry mouth, loss of appetite, and the smell of acetone in the exhaled air. If left untreated, hyperglycemia in type 1 diabetes mellitus can lead to the development of life-threatening diabetic ketoacidosis.

The insulin dose must be adjusted in case of thyroid dysfunction, Addison’s disease, hypopituitarism, impaired liver and kidney function, and in diabetes mellitus in patients over 65 years of age.

Due to the increased risk of cardiac and cerebral complications of hypoglycemia, the insulin preparation should be used with caution in patients with severe stenosis of the coronary and cerebral arteries.

Use with caution in patients with proliferative retinopathy, especially those not receiving photocoagulation (laser coagulation) treatment due to the risk of amaurosis (complete blindness).

If the patient increases the intensity of physical activity or changes their usual diet, adjustment of the insulin dose may be required.

Concomitant diseases, especially infections and conditions accompanied by fever, increase the need for insulin.

Transferring a patient to a new type of insulin or an insulin preparation from another manufacturer must be carried out under medical supervision.

When using insulin preparations in combination with thiazolidinedione group drugs in patients with type 2 diabetes mellitus, fluid retention in the body may occur, resulting in an increased risk of developing and progressing chronic heart failure, especially in patients with cardiovascular diseases and the presence of risk factors for chronic heart failure. Patients receiving such therapy should be regularly examined to identify signs of heart failure. If heart failure occurs, therapy should be carried out in accordance with current treatment standards.

Drug Interactions

The hypoglycemic effect of insulin is enhanced by oral hypoglycemic drugs, MAO inhibitors, ACE inhibitors, carbonic anhydrase inhibitors, non-selective beta-blockers, bromocriptine, octreotide, sulfonamides, anabolic steroids, tetracyclines, clofibrate, ketoconazole, mebendazole, pyridoxine, theophylline, cyclophosphamide, fenfluramine, lithium preparations, drugs containing ethanol.

The hypoglycemic effect of insulin is weakened by glucagon, somatropin, estrogens, oral contraceptives, glucocorticosteroids, iodine-containing thyroid hormones, thiazide diuretics, “loop” diuretics, heparin, tricyclic antidepressants, sympathomimetics, danazol, clonidine, epinephrine, histamine H₁-receptor blockers, slow calcium channel blockers, diazoxide, morphine, phenytoin, nicotine.

Under the influence of reserpine and salicylates, both weakening and enhancement of the action of insulin is possible.

Reduces tolerance to ethanol.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.