Inhaled Insulin available by the brand name of Afrezza (manufactured by Mannkind Corporation) is ultra-rapid acting insulin.

Inhaled insulin (Afrezza) Uses:

Both Type 1 and Type 2 diabetes:

• It is prescribed to treat diabetes mellitus (type 1 or type 2) in order to enhance and optimize glycemic control.

Inhaled Insulin dose in Adults:

Inhaled Insulin (Afrezza) Dose in the treatment of Diabetes mellitus:

• Note:
  • Patients' insulin needs vary, and therapy calls for dosage modifications under close physician supervision.
  • In patients with type 1 diabetes, inhaled insulin must be combined with long-acting (basal) insulin.

• Initial dose:

  • Insulin-naive patients: 4 units with each meal

  • Patients previously on SubQ mealtime (prandial) insulin:

    • 21 to 24 units injected dose per meal:

      • then 24 units per meal

    • 17 to 20 units injected dose per meal:

      • then 20 units per meal

    • 13 to 16 units injected dose per meal:

      • then  16 units per meal

    • 9 to 12 units injected dose per meal:

      • then  12 units per meal

    • 5 to 8 units injected dose per meal:

      • then  8 units per meal

    • ≤4 units injected dose per meal:

      • then 4 units per meal

• Patients previously on SubQ premixed insulin:
  • Calculating the mealtime injected dose involves equally dividing the day total of premixed insulin injections over the three meals.
  • Based on the scale below, convert each calculated injectable mealtime dose to a mealtime inhalation dose.
  • Additionally, provide half of the daily recommended amount of premixed injections as an injection of basal insulin.

  • 21 to 24 units injected dose per meal:

    • then 24 units per meal

  • 17 to 20 units injected dose per meal:

    • then 20 units per meal

  • 13 to 16 units injected dose per meal:

    • then 16 units per meal

  • 9 to 12 units injected dose per meal:

    • then 12 units per meal

  • 5 to 8 units injected dose per meal:

    • then 8 units per meal

  • ≤4 units injected dose per meal:

    • then 4 units per meal

Adjustment of dose:

• The dosage needs to be changed in order to achieve and maintain effective glucose control and avoid hypoglycemia.
• Based on metabolic requirements, findings of blood glucose monitoring, and the intended glycemic control objective, adjust insulin dosage.
• Carefully monitor blood sugar levels in patients who need high insulin inhalation dosages.
• Consider using the SubQ lunchtime insulin dose should blood glucose control cannot be attained by higher inhalation doses.
• Individualized monitoring and treatment plans are required.
• Adjustments to inhaled insulin are made in 4-unit steps.

The following dosage adjustments for injectable prandial insulin are necessary for type 2 diabetic patients:

• For hypoglycemia:

  • If there is no obvious cause for the hypoglycemia, reduce the dose by 10% to 20%; for severe hypoglycemia (requiring help from someone else or blood glucose below 40 mg/dL), reduce the dose by 20% to 40% of the actual dose.

• To reach self-monitoring glucose target:

  • Ten to fifteen percent of the dose should be changed.

Pregnancy Risk Category: C

• There is not much information available on the use of insulin inhaled during pregnancy.
• Diabetes that is not properly controlled can result in harmful maternal and fetal events such as preeclampsia, preterm births, problems, and severe birth abnormalities.
• Keeping maternal blood sugar and HbA1C as near to the goal levels as feasible before conception and during pregnancy to prevent negative effects. However, it's crucial to prevent severe hypoglycemia.
• Insulin requirements typically increase during pregnancy due to physiological changes brought on by pregnancy.
• This necessitates regular dosage changes and monitoring.
• After birth, insulin needs immediately decrease.
• Type 1 and type 2 diabetes mellitus are best managed throughout pregnancy with insulin. If pharmacologic therapy is required, it can also be applied to the treatment of gestational diabetes mellitus.
• Currently, alternatives to inhaled insulin are chosen.
• Consult the Insulin Regular monograph for more details on using insulin while pregnant.

Breastfeeding: Inhaled insulin

• Breast milk contains both endogenous and exogenous insulin (studies not done with this preparation).
• All females are encouraged to breastfeed, even those with gestational diabetes mellitus or type 2.
• Pregnant women with pregestational diabetics may benefit from a small snack prior to breastfeeding.
• According to the manufacturer breastfeeding during therapy is a decision that should be made after considering the risks to infants and the benefits to mothers.

Afrezza Dose in Kidney Disease:

• The drug manufacturer's label does not contain any dosage adjustments. (has not yet been studied).
• Take care.
• Increasing glucose monitoring and dose reductions might be necessary.

Afrezza Dose in Liver disease:

• The labeling of drug makers does not contain any dosage adjustments (has not yet been examined).
• Take care.
• Increasing glucose monitoring and dose reductions might be necessary.

Common Side Effects of Inhaled Insulin (Afrezza):

• Endocrine & metabolic:

  • Hypoglycemia

• Respiratory:

  • Acute bronchospasm
  • Cough

Less Common Side Effects of Inhaled Insulin (Afrezza):

• Genitourinary:

  • Urinary Tract Infection

• Endocrine & Metabolic:

  • Severe Hypoglycemia

• Central Nervous System:

  • Headache
  • Fatigue

• Respiratory:

  • Reduced Forced Expiratory Volume
  • Throat Irritation
  • Bronchitis
  • Decreased Lung Function
  • Productive Cough

• Gastrointestinal:

  • Sore Throat
  • Diarrhea
  • Nausea

Contraindications to Inhaled insulin (Afrezza):

• Allergies to the standard Insul or any different formulation ingredient
• If you have hypoglycemia,
• Bronchospasm can contribute to chronic lung conditions like COPD or asthma.
• There is not much evidence of insulin cross-reactivity with allergenic substances. Cross-sensitivity is possible due to similarities in chemical structure or pharmacologic effects.

Warnings and precautions

• Diabetic ketoacidosis

  • Diabetes ketoacidosis was more frequent with insulin inhaled than with the comparator insulin, according to clinical trials with type 1 diabetic patients. In individuals who are at a high risk for DKA (such as those with an acute sickness or infection), glucose monitoring should be increased. If other insulin delivery methods are required, do so.
  • For the treatment of diabetic ketoacidosis, insulin should not be breathed.

• Hypersensitivity

  • Anaphylaxis and severe, potentially life-threatening allergic reactions may be possible.
  • Cease taking the medication if you have hypersensitive responses, and provide supportive care to the patient instead until your symptoms get better.

• Hypoglycemia

  • Hypoglycemia is the most frequent side effect of insulin.
  • Different insulin formulations have different timings for hypoglycemia.
  • Hypoglycemia can be caused by increased exercise or work without eating. Insulin degludec, insulin detemir, and insulin glargine are examples of long-acting insulin formulations that may hinder hypoglycemia recovery.
  • Convulsions, coma, and temporary or irreversible brain injury can all result from hypoglycemia.
  • Illness, emotional distress, and other stressors can all have an impact on how much insulin is needed.
  • Patients should be instructed to use ethanol sparingly. It might make hypoglycemia more likely.

• Hypokalemia

  • Use caution while administering loop diuretics to patients at high risk of hypokalemia.
  • Patients with a high risk of hypoglycemia should have their serum potassium levels checked.
  • Hypokalemia can be brought on by insulin, which can move potassium from extracellular to intracellular regions.
  • If untreated, hypokalemia can result in respiratory paralysis, cardiac arrhythmia, and even death.

• Lung cancer:

  • It is not known if inhalation powder can cause lung or respiratory tract cancers.
  • Clinical trials revealed 2 cases in patients who had used heavy tobacco in the past. 2 additional cases were found in non-smokers after clinical trials were completed.
  • Patients with lung cancer or a history of it, as well as patients who are at high risk for developing lung cancer, should be cautious.
  • Rare cases of cancer have been reported.

• Deterioration of the pulmonary lung function

  • This could lead to a decrease in lung function (measured using FEV) over time.
  • Within the first three months of therapy, a decline was noticed. It lasted for up to 2 years and did not get worse.
  • Even in the absence of pulmonary symptoms, PFTs should be evaluated at baseline, six months following therapy, and annually thereafter.
  • Consider discontinuing if the FEV drops by >=20%
  • Patients with relentless or frequent wheezing, bronchospasm, or other breathing problems should be monitored frequently.
  • If the symptoms do not improve, discontinue using the product.

• Bariatric surgery

  • Hypoglycemia

    • In order to stop using diabetes medication or transition to non-hypoglycemic medications, regularly monitor insulin dosage during active weight loss.
      Following a sleeve gastroplasty, gastric band, or gastric bypass, hypoglycemia could happen.
      These methods may lead to a partial or complete return of normal insulin secretion and sensitivity.
    • Type 2 diabetes rates and times of improvement and resolution vary from one patient to the next.
    • Patients with severe b-cell dysfunction (fasting c0.3 nmol/L) should reduce their Insulin intake by at least 75% after gastric bypass.
    • Dose insulin cautiously and avoid bolus injections. In the early stages of operation, close clinical monitoring is advised.

  • Weight loss

    • Consider the risks and benefits of alternative therapies after gastric bypass, gastric banding, or sleeve-gastrectomy; weight gain can occur.

• Cardiac disease

  • Monitor for heart disease symptoms if PPAR-gamma agonists have been prescribed.
  • Consider reducing PPAR-gamma agonist doses or stopping therapy if heart failure occurs.
  • Use of peroxisome proliferator-activated receptor (PPAR), and gamma agonists (including Thiazolidinediones) concurrently with heart failure medications, such as insulin, can cause fluid retention due to dose.

• Chronic lung disease: [US-Boxed Warning]

  • Patients with COPD and asthma have been known to experience acute bronchospasm after inhaling insulin.
  • Patients with COPD or asthma are not advised to use this medication.
  • To identify any potential lung disease, you should conduct a thorough medical history, physical exam, and spirometry (FEV).

• Hepatic impairment

  • Patients with hepatic impairment should be cautious.
  • Patients may need to be monitored more often for glucose levels and may have their dosage requirements reduced.

• Renal impairment

  • Patients with impaired renal function should be cautious (has not been tested).
  • Patients may need to be monitored more often for glucose levels and may have their dosage requirements reduced.

Inhaled insulin: Drug Interaction

Monitoring parameters:

• HbA1C: At least twice a year in patients who are complying with their treatment regimen and have stable glycemic control. Patients who are not achieving their treatment objectives or whose therapy has changed every three months.
• Weight
• PFTs at baseline, 6 months after therapy began, and every year thereafter.
• Patients who have bronchospasm, chronic or recurrent wheezing, or other breathing issues should be closely watched.
• Renal function
• Hepatic function
• Patients at high risk of DKA (eg, acute disease or infection) should be monitored more frequently.
• Plasma glucose
• Electrolytes

How to administer Inhaled insulin (Afrezza)?

• Only for oral inhalation
• Dispense at the start of each meal.
• Count out how many cartridges are needed for a single dose. To achieve the proper dosage, several cartridges can be required.
• Allow cartridges to rest at room temperature for 10 min.
• Snap the cap to the inhaler.
• Place the inhaler at the top with the mouthpiece up and the base on the bottom.
• Inhaler inversion, holding the mouthpiece pointed down, shaking the inhaler, dropping the cartridge, and before administering doses can lead to loss of drug.
• The inhaler must be replaced if any of these events occur.
• Breathe deeply.
• Keep your lips closed around the mouthpiece and do not inhale.
• Maintain a straight back and incline the inhaler downward. Breathe in steadily, swiftly, and profoundly.
• Keep your breath inhaling for as long as you feel relaxed while simultaneously releasing the inhaler.
• Continue to inhale, and then continue to breathe normally.
• Empty cartridges should be thrown away by taking them out of the base. Do not keep the inhaler in there.
• For the correct dose, repeat the steps for each cartridge; only one inhaler is needed for multiple cartridges.
• To ensure accurate drug delivery, the inhaler should be replaced every 15 days.

Mechanism of action of Inhaled insulin (Afrezza):

• Insulin controls the metabolism of proteins and carbohydrates by attaching to particular membrane receptors.
• The liver, skeletal muscles, and adipose tissues are the insulin target organs.
• Insulin stimulates the liver's production of hepatic glycogen.
• Insulin stimulates the production of fatty acids in the liver, which is then released into the bloodstream as lipoproteins.
• Insulin can cause increased protein synthesis in the skeleton and greater glycogen synthesis.
• Insulin stimulates insulin metabolism in adipose tissues to produce fatty acids. It also facilitates triglyceride storage and synthesis by adipocytes.
• Additionally, it prevents triglyceride hydrolysis.
• Insulin speeds up cellular absorption by increasing cellular permeability to numerous ions, such as potassium, magnesium, and phosphate. Sodium-potassium ATPases are activated by insulin, which enhances intracellular potassium transport.
• Insulin products, which are normally secreted by pancreas cells, can be manufactured using recombinant DNA technology that uses either Saccharomyces cerevisiae or E. coli.
• The structure of human insulin that is breathed is comparable to that of native insulin. The carrier particles that it is adsorbed upon disintegrate in the lungs. This makes it possible for the systemic circulation to quickly absorb insulin.
• Based on the beginning, peak, and duration of their effects, insulins can be categorized (e.g. rapid-, short, intermediate- and long-acting insulin). Inhaled insulin works quite quickly.

Pharmacokinetic note

• The carrier particles are not digested after entering your lungs and being absorbed. They are removed from the urine unaltered.
• In order to assess the pharmacokinetic profile, dosages of 4, 12, and 48 units were examined.

The onset of action:

• 12 mins; Peak effect: 35 to 55 mins

Duration:

• ~90 to 270 minutes (proportional to dose)

Bioavailability:

• 21 to 30 percent more than ordinary SubQ insulin.

Half-life elimination:

• 120 to 206 minutes (apparent terminal half-life)

Time to peak, plasma:

• 10 to 20 minutes

Excretion:

• Urine

International Brands of Inhaled insulin:

• Afrezza

Inhaled Insulin Cost in the US:

Afrezza Powder for Inhalation:

Every 4 units: $4.72

Each 4 & 8 & 12 units: $9.44

Every 8 units: $9.44

Every 12 units: $14.16

Each 90 x 4 units & 90x8 units: $7.08

Each 90 x 8 units & 90x12 units: $11.80

Inhaled insulin Brand Names in Pakistan:

No Brands Available in Pakistan.