Actraphane (Biphasic Isophane Insulin)

Premixed human insulin for the treatment of diabetes mellitus

Rx - Prescription ATC: A10AD01 Insulin – Intermediate + Fast-acting
Active Ingredient
Biphasic isophane insulin (human, rDNA)
Available Forms
Suspension for injection
Strengths
40 IU/ml, 100 IU/ml
Known Brands
Actraphane 30, Actraphane 30 FlexPen, Actraphane 30 Penfill, Actraphane 30 InnoLet, Actraphane 50 Penfill
Medically reviewed | Last reviewed: | Evidence level: 1A
Actraphane is a premixed biphasic human insulin produced by Novo Nordisk using recombinant DNA technology. It contains a fixed-ratio combination of fast-acting soluble insulin and intermediate-acting isophane (NPH) insulin, providing both rapid mealtime glucose control and sustained basal insulin coverage. Actraphane is used in the management of diabetes mellitus in patients who require insulin therapy, including both type 1 and type 2 diabetes. It is listed among the World Health Organization's essential insulin formulations for global diabetes care.
Published:
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Written and reviewed by iMedic Medical Editorial Team | Specialists in Endocrinology

Quick Facts about Actraphane

Active Ingredient
Biphasic Insulin
Human, rDNA origin
Drug Class
Insulin
Intermediate + fast-acting
ATC Code
A10AD01
Insulin (human)
Common Uses
Diabetes
Type 1 & Type 2
Available Forms
Injection
Suspension, SC
Prescription Status
Rx Required
Prescription only

Key Takeaways about Actraphane

  • Premixed convenience: Actraphane combines fast-acting and intermediate-acting insulin in a single injection, simplifying regimens for patients who need both mealtime and basal insulin coverage
  • Inject before meals: Actraphane should be administered subcutaneously within 30 minutes before a meal to allow the soluble insulin component to coincide with postprandial glucose rise
  • Always resuspend before use: The suspension must be gently rolled and inverted at least 20 times before each injection until uniformly white and cloudy – never shake vigorously
  • Monitor blood glucose regularly: Hypoglycaemia is the most common adverse effect; regular self-monitoring helps detect and prevent low blood sugar episodes
  • Never switch insulin without guidance: Changing between insulin brands, types, or strengths must always be done under medical supervision to avoid dangerous blood glucose fluctuations

What Is Actraphane and What Is It Used For?

Actraphane is a premixed biphasic human insulin used to treat diabetes mellitus. It contains a fixed combination of 30% soluble insulin (fast-acting) and 70% isophane insulin (intermediate-acting), providing both rapid postprandial glucose control and sustained basal insulin coverage in a single injection. It is indicated for patients with type 1 or type 2 diabetes who require insulin therapy.

Actraphane belongs to the pharmacological class of insulins and analogues for injection, specifically categorised as an intermediate-acting insulin combined with a fast-acting insulin. The medication is manufactured by Novo Nordisk, a global leader in diabetes care, using recombinant DNA (rDNA) technology in Saccharomyces cerevisiae (baker's yeast). This biosynthetic production method ensures a high-purity human insulin that is structurally identical to the insulin naturally produced by the human pancreas, minimising the risk of immunogenic reactions.

The name "Actraphane 30" reflects the composition: 30% fast-acting soluble human insulin and 70% intermediate-acting isophane human insulin (also known as NPH insulin – Neutral Protamine Hagedorn). The soluble fraction provides a rapid onset of action, working within approximately 30 minutes of injection to manage the blood glucose rise that occurs after eating. The isophane fraction has a delayed onset and prolonged duration, providing background insulin coverage for up to 24 hours. This dual-action profile means that Actraphane can address both the prandial (mealtime) and basal insulin requirements with a single injection.

Actraphane is available in several delivery formats designed to meet different patient needs and preferences:

  • Actraphane 30 Penfill: A 3 ml cartridge (300 IU) for use with Novo Nordisk reusable insulin pens such as NovoPen
  • Actraphane 30 FlexPen: A prefilled disposable pen containing 3 ml (300 IU) – ready to use without cartridge insertion
  • Actraphane 30 InnoLet: A prefilled disposable pen with a large, easy-to-read dose dial, designed for patients with impaired vision or dexterity
  • Actraphane 50 Penfill: A 3 ml cartridge containing a 50:50 mixture of soluble and isophane insulin, providing stronger mealtime coverage
  • Actraphane 30 vials: 10 ml vials (40 IU/ml) for use with insulin syringes, available in some markets

Diabetes mellitus is a chronic metabolic disorder characterised by elevated blood glucose levels resulting from deficient insulin secretion (type 1 diabetes), impaired insulin action (type 2 diabetes), or both. According to the International Diabetes Federation (IDF), approximately 537 million adults worldwide were living with diabetes in 2021, a figure projected to rise to 783 million by 2045. Insulin therapy remains the cornerstone of treatment for type 1 diabetes and is increasingly necessary for patients with type 2 diabetes whose blood glucose cannot be adequately controlled with oral medications alone.

The premixed formulation of Actraphane offers several practical advantages for patients and clinicians. By combining two insulin types in a single product, it reduces the number of daily injections required and eliminates the need for patients to manually mix insulin themselves – a process that can introduce dosing errors. This simplification is particularly beneficial for elderly patients, those with limited health literacy, and patients in resource-limited settings where access to complex insulin regimens and diabetes education may be restricted.

WHO Essential Medicine

Human insulin, including biphasic formulations such as Actraphane, is listed on the WHO Model List of Essential Medicines (2023). The WHO recognises insulin as a critical medication for global diabetes care, and premixed insulin preparations play a vital role in settings where basal-bolus regimens are impractical or unavailable.

What Should You Know Before Taking Actraphane?

Before starting Actraphane, your doctor must determine the correct dose based on your blood glucose levels, lifestyle, and any other medications. Do not use Actraphane if you are allergic to human insulin or any of its excipients. Never use Actraphane if the suspension does not appear uniformly white and cloudy after mixing, or if it has been frozen.

Insulin therapy requires careful initiation and ongoing management. Your doctor will work with you to determine the appropriate starting dose, injection timing, and blood glucose monitoring schedule. Successful insulin therapy also depends on patient education: understanding how to inject correctly, recognise and treat hypoglycaemia, adjust doses based on activity and food intake, and store insulin properly are all essential skills.

Contraindications

You must not use Actraphane if you have a known hypersensitivity (allergy) to human insulin, protamine sulphate, metacresol, or any of the other excipients listed in the formulation. Allergic reactions to insulin are uncommon but can range from localised injection site reactions to rare systemic anaphylaxis.

Actraphane must never be used during episodes of hypoglycaemia (low blood sugar). If your blood glucose is already low, administering additional insulin will further decrease it to potentially dangerous levels. Always check your blood glucose before injecting if you suspect hypoglycaemia.

Actraphane must not be administered intravenously. It is a suspension formulation intended exclusively for subcutaneous injection. Intravenous injection of insulin suspensions can cause severe, potentially life-threatening reactions. Additionally, Actraphane must not be used in insulin infusion pumps, as the isophane component can precipitate and block the pump tubing.

Warnings and Precautions

Talk to your doctor, pharmacist, or diabetes nurse before using Actraphane if any of the following apply:

  • Hypoglycaemia awareness: Some patients, particularly those with long-standing diabetes or those taking beta-blockers, may have reduced awareness of the warning signs of low blood sugar. This condition, known as hypoglycaemia unawareness, increases the risk of severe hypoglycaemic episodes. Your doctor may recommend more frequent blood glucose monitoring.
  • Kidney or liver disease: Impaired kidney or liver function can slow the metabolism and clearance of insulin, leading to prolonged glucose-lowering effects. Dose reductions and more intensive monitoring may be required.
  • Changing insulin regimen: Switching between different insulin brands, types (e.g., from human insulin to insulin analogues), or strengths can affect your blood glucose control and must be done under close medical supervision. A dose change may be needed with the first injection or may become necessary over several weeks.
  • Physical activity and diet: Changes in physical activity level, meal composition, or meal timing can significantly affect your insulin requirements. Increased exercise generally lowers blood glucose and may require a dose reduction, while illness or reduced activity may increase requirements.
  • Travel across time zones: When travelling across multiple time zones, your insulin injection schedule may need adjustment. Consult your doctor before travelling, and carry a letter confirming your need for insulin and injection supplies.
  • Thiazolidinedione combination: Using Actraphane in combination with thiazolidinediones (pioglitazone, rosiglitazone) may increase the risk of heart failure due to fluid retention. Report any new swelling, weight gain, or breathlessness to your doctor immediately.

Pregnancy and Breastfeeding

If you are pregnant, planning a pregnancy, or breastfeeding, discuss your insulin therapy with your doctor. Good blood glucose control is essential during pregnancy for the health of both mother and baby. Poorly controlled diabetes during pregnancy is associated with increased risks of congenital abnormalities, macrosomia (abnormally large baby), neonatal hypoglycaemia, and other complications.

Human insulin (including Actraphane) does not cross the placenta and is not considered teratogenic. It is therefore widely used during pregnancy. However, insulin requirements typically decrease during the first trimester, increase during the second and third trimesters, and fall rapidly after delivery. Close blood glucose monitoring and frequent dose adjustments throughout pregnancy are essential.

Breastfeeding poses no risk to the infant from the mother's insulin therapy. Insulin is a large protein molecule that is broken down in the infant's gastrointestinal tract if ingested through breast milk. However, the mother's insulin dose and dietary requirements may need adjustment during breastfeeding, as lactation can lower blood glucose levels.

Driving and Machinery

Hypoglycaemia can impair your ability to concentrate and react, making driving and operating machinery dangerous. Always check your blood glucose before driving, and do not drive if your blood glucose is low or if you are experiencing symptoms of hypoglycaemia. Carry fast-acting glucose (e.g., glucose tablets, sugary drink) in your vehicle at all times.

How Does Actraphane Interact with Other Drugs?

Several medications can affect how Actraphane works. Some drugs lower blood glucose further and may increase the risk of hypoglycaemia (e.g., oral antidiabetics, ACE inhibitors, MAO inhibitors). Others raise blood glucose and may require a dose increase (e.g., corticosteroids, thiazide diuretics, thyroid hormones). Beta-blockers can mask hypoglycaemia symptoms. Always inform your doctor about all medications and supplements you take.

Insulin interacts with a wide range of medications because blood glucose regulation is influenced by many physiological systems. Understanding these interactions is crucial for safe and effective diabetes management. Your healthcare provider will consider all of your medications when determining and adjusting your Actraphane dose.

The following table summarises the most important known drug interactions with Actraphane:

Known Drug Interactions with Actraphane
Interacting Drug Effect on Blood Glucose Clinical Significance Recommendation
Oral antidiabetic agents (metformin, sulfonylureas, SGLT2 inhibitors) Lower blood glucose – additive hypoglycaemic effect Major Monitor blood glucose closely; insulin dose reduction may be required
ACE inhibitors (enalapril, ramipril, lisinopril) May lower blood glucose and enhance insulin sensitivity Moderate Monitor blood glucose; may need to reduce insulin dose
Beta-blockers (propranolol, atenolol, metoprolol) May mask symptoms of hypoglycaemia (tremor, tachycardia) Major Increase blood glucose monitoring frequency; educate patient on non-adrenergic hypoglycaemia symptoms
Corticosteroids (prednisolone, dexamethasone) Raise blood glucose significantly (glucocorticoid effect) Major Substantial insulin dose increase usually required; monitor closely
Thiazide diuretics (hydrochlorothiazide, indapamide) Raise blood glucose by impairing insulin secretion Moderate Monitor blood glucose; insulin dose increase may be needed
MAO inhibitors Lower blood glucose – enhanced insulin effect Moderate Monitor blood glucose closely during co-administration
Thyroid hormones (levothyroxine) Raise blood glucose by increasing metabolic rate Moderate Reassess insulin dose when thyroid therapy is initiated or changed
Alcohol May initially raise then lower blood glucose; impairs hepatic gluconeogenesis Major Advise moderation; never drink on empty stomach; monitor glucose

Important Considerations for Drug Interactions

The interactions listed above are not exhaustive. Many other medications can affect blood glucose levels to varying degrees. It is particularly important to be aware that starting, stopping, or changing the dose of any co-administered medication may alter your insulin requirements. Some common examples include:

  • Salicylates (aspirin) in high doses can lower blood glucose by enhancing insulin secretion
  • Octreotide and lanreotide (somatostatin analogues) may increase or decrease insulin requirements depending on the underlying condition
  • Danazol has hyperglycaemic effects and may necessitate an insulin dose increase
  • Sympathomimetics (salbutamol, terbutaline) can raise blood glucose as a beta-2 adrenergic effect

Always carry an up-to-date list of all your medications (including over-the-counter drugs, herbal supplements, and vitamins) and show it to every healthcare professional you consult. This helps prevent potentially dangerous interactions and ensures your insulin therapy remains safe and effective.

What Is the Correct Dosage of Actraphane?

Actraphane dosage is highly individualised based on each patient's blood glucose levels, lifestyle, diet, and other medical conditions. It is typically injected subcutaneously once or twice daily, 30 minutes before a meal. The dose is measured in international units (IU) and is determined and adjusted by your doctor based on regular blood glucose monitoring. Never change your dose without medical advice.

There is no single "correct" dose of Actraphane that applies to all patients. Insulin requirements vary enormously between individuals, influenced by factors such as body weight, physical activity, diet, remaining beta-cell function, insulin sensitivity, concurrent medications, and the presence of intercurrent illness. Your doctor will start you on a carefully calculated initial dose and then adjust it based on your blood glucose readings over subsequent days and weeks.

Adults

General Dosage Guidelines for Adults
Diabetes Type Typical Starting Dose Administration Notes
Type 1 Diabetes 0.5–1.0 IU/kg/day (total daily insulin) Usually twice daily (before breakfast and dinner), 30 min before meal Part of a regimen that may also include rapid-acting insulin at other meals; dose split typically 2/3 morning, 1/3 evening
Type 2 Diabetes (insulin-requiring) 0.2–0.6 IU/kg/day (total daily insulin) Once or twice daily, 30 min before meal Often combined with metformin; start conservatively and titrate upward based on glucose targets

For patients with type 1 diabetes, the total daily insulin requirement is typically between 0.5 and 1.0 IU per kilogram of body weight per day, though this can vary significantly. During the "honeymoon period" shortly after diagnosis, residual beta-cell function may mean that insulin requirements are lower. Over time, as autoimmune destruction of beta cells progresses, requirements generally increase. Actraphane may be used as part of a twice-daily injection regimen, though many patients with type 1 diabetes ultimately require a basal-bolus regimen with multiple daily injections or an insulin pump for optimal control.

For patients with type 2 diabetes who are starting insulin, a conservative approach is typically taken. The initial dose is often 10–20 IU once or twice daily (or approximately 0.2 IU/kg/day), with gradual uptitration based on fasting and pre-meal blood glucose targets. This cautious approach minimises the risk of hypoglycaemia, which is the most common and most feared adverse effect of insulin therapy.

Children

Actraphane can be used in children and adolescents with diabetes. In paediatric patients with type 1 diabetes, the total daily insulin requirement is typically 0.5–1.5 IU per kilogram of body weight per day, though requirements increase significantly during puberty due to growth hormone-mediated insulin resistance. A child who was well-controlled on 0.5 IU/kg/day before puberty may need 1.0–1.5 IU/kg/day during the pubertal growth spurt.

Dosing in children must be determined by a paediatric endocrinologist or diabetologist with experience in insulin therapy. The risk of hypoglycaemia is of particular concern in young children, who may not be able to recognise or communicate their symptoms. Parents and caregivers must be trained in hypoglycaemia recognition and management, including the use of glucagon for severe episodes.

Elderly

Elderly patients with diabetes require special consideration when initiating or adjusting insulin therapy. Age-related changes in kidney function, hepatic metabolism, and counter-regulatory hormone responses can increase the risk and severity of hypoglycaemia. Additionally, many elderly patients take multiple medications that may interact with insulin.

In elderly patients, it is generally advisable to start with a lower dose and titrate more slowly, accepting slightly higher blood glucose targets to reduce the risk of hypoglycaemia. The International Diabetes Federation (IDF) and the American Diabetes Association (ADA) recommend relaxed glycaemic targets for frail elderly patients, with a focus on avoiding symptomatic hyperglycaemia and hypoglycaemia rather than achieving strict HbA1c goals.

Missed Dose

If you forget to inject your Actraphane dose before a meal, do not take a double dose to compensate. Missing a dose may cause your blood glucose to rise (hyperglycaemia). If you realise you have missed a dose shortly after the meal, consult your diabetes healthcare team for advice. They may recommend a reduced dose of rapid-acting insulin to cover the meal, or they may advise you to simply monitor your blood glucose and resume your normal dosing schedule at the next meal.

Consistent adherence to your insulin injection schedule is important for maintaining good blood glucose control. Consider setting alarms or reminders to help you remember your doses. If you frequently forget doses, discuss this with your healthcare team, as they may be able to simplify your regimen.

Overdose

An overdose of insulin causes hypoglycaemia (low blood sugar), which can range from mild (easily self-treated) to severe (life-threatening). There is no specific defined overdose threshold for insulin, as the glucose-lowering effect depends on concurrent food intake and physical activity.

Treating Insulin Overdose / Severe Hypoglycaemia

Mild hypoglycaemia: Consume 15–20 grams of fast-acting carbohydrate (e.g., 3–4 glucose tablets, 150 ml of fruit juice, or a sugary drink). Recheck blood glucose after 15 minutes and repeat if still below 4 mmol/L (72 mg/dL).

Severe hypoglycaemia (loss of consciousness, seizure, inability to swallow): Do NOT attempt to give food or drink by mouth. An accompanying person should administer glucagon 1 mg intramuscularly or subcutaneously and call emergency services immediately. Once conscious, the patient should consume oral carbohydrates to prevent recurrence.

What Are the Side Effects of Actraphane?

The most common side effect of Actraphane is hypoglycaemia (low blood sugar), which can occur if the dose is too high, a meal is missed or delayed, or physical activity is greater than usual. Other possible side effects include injection site reactions, lipodystrophy (changes in fat tissue at injection sites), allergic reactions, and visual disturbances when starting therapy. Most side effects are manageable with proper technique and monitoring.

Like all insulins, Actraphane can cause side effects, though not everyone experiences them. The safety profile of human insulin is well-established through decades of clinical use, and serious adverse effects are uncommon when the medication is used correctly. Proper injection technique, regular blood glucose monitoring, appropriate dose adjustments, and rotation of injection sites are all important strategies for minimising side effects.

Seek immediate medical attention if you experience:

Signs of severe hypoglycaemia (confusion, seizures, loss of consciousness) or signs of a severe allergic reaction (generalised skin rash, facial or throat swelling, difficulty breathing, rapid heartbeat, low blood pressure). Severe hypoglycaemia is a medical emergency – an accompanying person should administer glucagon and call emergency services.

Very Common Side Effects

May affect more than 1 in 10 users
  • Hypoglycaemia (low blood sugar) – symptoms include sweating, trembling, hunger, confusion, dizziness, palpitations, anxiety, pallor, blurred vision, and weakness

Common Side Effects

May affect up to 1 in 10 users
  • Injection site reactions (redness, swelling, itching, pain at the injection site)
  • Lipodystrophy at injection site (lipohypertrophy – fatty lumps; lipoatrophy – loss of fat tissue) due to repeated injections at the same site

Uncommon Side Effects

May affect up to 1 in 100 users
  • Visual disturbances (temporary blurred vision, usually when starting insulin therapy – resolves as blood glucose stabilises)
  • Peripheral oedema (swelling of ankles and feet, especially when starting insulin after a period of poor glucose control)
  • Localised allergic reactions at injection site (urticaria, redness)

Rare Side Effects

May affect up to 1 in 1,000 users
  • Generalised allergic reactions (generalised urticaria, angioedema, bronchospasm, hypotension, anaphylaxis)
  • Diabetic peripheral neuropathy (rarely, rapid improvement in blood glucose control may temporarily worsen existing neuropathy)

Very Rare Side Effects

May affect up to 1 in 10,000 users
  • Anaphylactic shock (life-threatening allergic reaction requiring immediate emergency treatment)
  • Insulin antibody formation (high titres are very rare with human insulin and rarely affect clinical efficacy)

Understanding Hypoglycaemia

Hypoglycaemia is the most important and most common side effect of insulin therapy. It occurs when blood glucose falls below approximately 3.9 mmol/L (70 mg/dL). The symptoms of hypoglycaemia are caused by the body's counter-regulatory response (adrenergic symptoms) and by insufficient glucose supply to the brain (neuroglycopenic symptoms):

  • Adrenergic symptoms (early warning signs): Sweating, trembling, palpitations, hunger, anxiety, pallor, nausea
  • Neuroglycopenic symptoms (more severe): Difficulty concentrating, confusion, unusual behaviour, visual disturbances, speech difficulties, drowsiness, seizures, loss of consciousness

Risk factors for hypoglycaemia include missed or delayed meals, excessive insulin dose, increased physical activity, alcohol consumption, and impaired kidney or liver function. Patients with long-standing diabetes may develop hypoglycaemia unawareness, a condition in which the usual warning symptoms are diminished or absent. This is particularly dangerous as the patient may progress directly to severe neuroglycopenic symptoms without the typical adrenergic warning signs.

Injection Site Reactions and Lipodystrophy

Local reactions at the injection site (redness, swelling, itching) are usually mild and transient, often resolving within a few days to weeks as the body adapts to treatment. Lipodystrophy – abnormal changes in the subcutaneous fat tissue at injection sites – can occur with repeated injections in the same area. Lipohypertrophy (fatty lumps) is more common than lipoatrophy (loss of fat tissue) and can affect insulin absorption, leading to unpredictable blood glucose levels. Systematic rotation of injection sites within and between injection areas (abdomen, thighs, upper arms, buttocks) is essential for prevention.

Reporting Side Effects

If you experience any side effects, including those not listed here, talk to your doctor, pharmacist, or diabetes nurse. You can also report side effects to your national medicines regulatory authority. Reporting helps improve knowledge about the safety of medications and benefits other patients.

How Should You Store Actraphane?

Unopened Actraphane should be stored in a refrigerator at 2–8°C (36–46°F). Do not freeze. Once in use, pens and cartridges can be kept at room temperature (below 25°C / 77°F) for up to 6 weeks. Protect from direct sunlight and heat. Do not use if the suspension does not become uniformly white and cloudy after gentle mixing.

Proper storage of insulin is essential to maintain its potency and safety. Insulin is a protein that can be denatured (destroyed) by extreme temperatures, freezing, and direct sunlight. Using improperly stored insulin can lead to unpredictable blood glucose control and potentially dangerous hyperglycaemia or hypoglycaemia.

Follow these storage guidelines for Actraphane:

  • Before first use (unopened): Store in a refrigerator at 2–8°C (36–46°F). Keep in the outer carton to protect from light. Do not store near the cooling element or freezer compartment. Do not freeze – frozen insulin must be discarded as freezing damages the insulin protein structure irreversibly.
  • During use (opened): Actraphane in use (carried as a spare or mounted in a pen) can be kept at room temperature (not above 25°C / 77°F) for up to 6 weeks. Do not refrigerate the pen in current use, as cold insulin injections can be more painful. Keep the pen cap on when not in use to protect from light.
  • Inspection before use: Before each injection, inspect the suspension after resuspending. It should appear uniformly white and cloudy. Do not use if it remains clear, contains visible solid white particles or clumps, or has a brownish discolouration.
  • Expiry date: Do not use Actraphane after the expiry date printed on the label and carton. The expiry date refers to the last day of that month.
  • Disposal: Do not dispose of insulin in wastewater or household waste. Return unused or expired insulin to your pharmacy for safe disposal. Used needles should be placed in a sharps container.
Travel Tips

When travelling, carry your insulin in your hand luggage (aircraft hold temperatures can drop below freezing). Use an insulated travel case to protect insulin from temperature extremes. Carry a medical letter from your doctor confirming your need for insulin and injection devices, as security regulations may require documentation for needles and syringes.

What Does Actraphane Contain?

Actraphane contains the active substance biphasic isophane insulin (human, produced by recombinant DNA technology in Saccharomyces cerevisiae). The Actraphane 30 formulation comprises 30% soluble insulin and 70% isophane insulin suspension. Inactive ingredients include protamine sulphate, zinc chloride, glycerol, metacresol, phenol, disodium phosphate dihydrate, sodium hydroxide, hydrochloric acid, and water for injections.

Understanding the composition of your insulin is important for identifying potential allergens and understanding how the medication works. Below is a detailed breakdown of what Actraphane contains.

Active Ingredient

The active substance is biphasic isophane insulin (human), produced biosynthetically using recombinant DNA technology in Saccharomyces cerevisiae (baker's yeast). Each millilitre of Actraphane 30 contains 100 IU (international units) of human insulin, comprising:

  • 30% soluble human insulin: The fast-acting component that begins working within 30 minutes of injection, with peak effect at 2–4 hours
  • 70% isophane human insulin (NPH): The intermediate-acting component complexed with protamine, providing a delayed onset (approximately 1.5 hours) and prolonged duration of action (up to 24 hours)

Inactive Ingredients (Excipients)

  • Protamine sulphate: A protein derived from fish sperm that binds to insulin to form the isophane (NPH) complex, delaying absorption and extending duration of action. Patients with fish allergy should discuss this with their doctor.
  • Zinc chloride: A stabiliser that helps maintain the hexameric structure of insulin crystals
  • Glycerol: An isotonic agent that ensures the injection has the same osmolarity as body fluids, reducing injection site pain
  • Metacresol: An antimicrobial preservative that prevents bacterial contamination after the first use
  • Phenol: An additional antimicrobial preservative
  • Disodium phosphate dihydrate: A buffering agent that maintains stable pH
  • Sodium hydroxide / hydrochloric acid: Used for pH adjustment to approximately 7.4 (physiological pH)
  • Water for injections: The vehicle in which all components are suspended
Protamine and Fish Allergy

Protamine sulphate, used to create the isophane (NPH) insulin complex, is derived from fish sperm. While allergic reactions to protamine in insulin preparations are extremely rare, patients with known fish allergy should inform their doctor before starting Actraphane. Your doctor may consider alternative insulin formulations that do not contain protamine.

Frequently Asked Questions about Actraphane

Actraphane is a premixed biphasic insulin used to treat diabetes mellitus in patients who require insulin therapy. It contains a combination of fast-acting soluble insulin (30%) and intermediate-acting isophane insulin (70%), providing both rapid mealtime glucose control and sustained background insulin coverage. It is used in both type 1 diabetes (where the body produces no insulin) and type 2 diabetes (where insulin production is insufficient or the body is resistant to its effects).

Before injection, gently roll the pen or cartridge between your palms and turn it upside down at least 20 times until the liquid appears uniformly white and cloudy. Never shake vigorously. Inject subcutaneously (under the skin) into the thigh, abdomen, upper arm, or buttock. Rotate injection sites systematically to prevent lipodystrophy. Administer within 30 minutes before a meal. After injecting, hold the needle under the skin for at least 6 seconds to ensure the full dose is delivered.

The number indicates the percentage of fast-acting soluble insulin. Actraphane 30 contains 30% soluble insulin and 70% isophane (NPH) insulin, while Actraphane 50 contains 50% soluble and 50% isophane insulin. Actraphane 50 provides a stronger and more pronounced mealtime blood glucose reduction, while Actraphane 30 provides more sustained background insulin coverage. Your doctor will select the formulation that best matches your individual blood glucose profile and eating patterns.

Hypoglycaemia (low blood sugar) symptoms include sweating, trembling, hunger, dizziness, confusion, palpitations, anxiety, and blurred vision. If you experience these symptoms, immediately consume 15–20 grams of fast-acting carbohydrate (glucose tablets, fruit juice, or a sugary drink). Recheck your blood glucose after 15 minutes and repeat if still low. For severe hypoglycaemia with loss of consciousness, an accompanying person should administer glucagon and call emergency services. Always carry fast-acting glucose with you.

Yes, human insulin (including Actraphane) is widely used during pregnancy and is considered safe. Good blood glucose control is essential during pregnancy for the health of both mother and baby. However, insulin requirements change throughout pregnancy – typically decreasing in the first trimester, increasing in the second and third trimesters, and dropping rapidly after delivery. Close monitoring and frequent dose adjustments by your healthcare team are essential throughout pregnancy.

Unopened Actraphane should be stored in a refrigerator at 2–8°C (36–46°F). Do not freeze. Once in use, pens and cartridges can be kept at room temperature (below 25°C / 77°F) for up to 6 weeks. Always keep the pen cap on when not in use to protect from light. Before each injection, check that the suspension appears uniformly white and cloudy after gentle resuspension. Discard if clumps, particles, or discolouration are visible.

References

All medical information in this article is based on peer-reviewed research, international clinical guidelines, and authoritative pharmaceutical references. The following sources were used:

  1. World Health Organization (WHO). Model List of Essential Medicines – 23rd list (2023). Geneva: WHO; 2023.
  2. European Medicines Agency (EMA). Actraphane – Summary of Product Characteristics. Novo Nordisk; 2024.
  3. International Diabetes Federation (IDF). IDF Diabetes Atlas, 10th Edition. Brussels: IDF; 2021.
  4. American Diabetes Association (ADA). Standards of Medical Care in Diabetes – 2024. Diabetes Care. 2024;47(Suppl 1):S1–S321.
  5. NICE (National Institute for Health and Care Excellence). Type 1 diabetes in adults: diagnosis and management (NG17). Updated 2022.
  6. NICE. Type 2 diabetes in adults: management (NG28). Updated 2022.
  7. Holt RIG, et al. The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2021;64(12):2609–2652.
  8. Davies MJ, et al. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the ADA and EASD. Diabetologia. 2022;65(12):1925–1966.
  9. Novo Nordisk. Actraphane 30 FlexPen – Patient Information Leaflet. 2024.
  10. British National Formulary (BNF). Biphasic isophane insulin (human). NICE/BNF; 2025.

Editorial Team

This article was written and medically reviewed by the iMedic Medical Editorial Team, comprising licensed physicians specialising in endocrinology, diabetology, and clinical pharmacology.

Medical Writing

iMedic Medical Editorial Team
Specialists in Endocrinology

Medical Review

iMedic Medical Review Board
Independent medical expert panel

Evidence Standard

Level 1A Evidence
GRADE Framework Applied

Guidelines Followed

WHO, EMA, ADA, IDF
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