Iloprost Injection for Frostbite: Dose, Indications, Administration, Side-Effects, and Pharmacology

Overview

High-latitude regions can experience frostbite, which can hurt the health of indigenous people who live in northern settlements and those who work in polar zones. Amputation is one of the worst outcomes that can result from frostbite, an injury that occurs in cold environments. Iloprost injection was authorized by the US (United States) Food and Drug Administration in 2023 to treat severe adult frostbite and lower the risk of amputation of the fingers or toes. With this approval, patients now have access to the first-ever severe frostbite treatment option.

Drug Group:

Iloprost is a member of the pharmacological class known as prostacyclin analogs. The body naturally produces molecules called prostacyclins, which are involved in vasodilation (the widening of blood vessels) and platelet aggregation (clumping of blood cells). Iloprost imitates these processes, offering medical advantages under certain circumstances.

Available Doses and Dosage Forms:

• Injection: One dosing vial containing 100 micrograms per milliliter (mcg/mL).

• Inhalation Solution: Single-dose ampules containing either ten mcg/mL or 20 mcg/mL.

For Patients:

What Is Severe Frostbite?

Prolonged exposure to cold conditions can induce frostbite, in which the skin and underlying tissues freeze. There are several phases to it, the most serious of which is severe frostbite. This may cause harm to the afflicted regions, resulting in burning, discomfort, numbness, and, in extreme situations, tissue death. In extreme situations, there is no longer any blood supply to the damaged region, which can result in tissue death and even necessitate amputation.

How Does Iloprost Injection Work?

Iloprost improves blood flow and dilates blood vessels, which can assist in improving circulation in the afflicted regions. This increased blood flow may facilitate healing and lower the possibility of frostbite-related problems. It may also be useful in the treatment of other illnesses, such as pulmonary arterial hypertension (PAH) (high blood pressure in the lungs).

What Is the Dosage of Iloprost Injection?

Iloprost injection dosages might change based on the ailment being treated and how each patient reacts to the drug. It is usually given as a continuous intravenous infusion over a few days in a hospital environment. Iloprost injection is often administered as a continuous intravenous infusion over six hours every day for a maximum of eight days in a row.

How Effective Is Iloprost Injection?

Iloprost injection efficacy varies from patient to patient. Iloprost has been proven in clinical studies to help individuals with illnesses, including Raynaud's phenomenon (feeling numb and cold in certain body parts due to cold temperature), frostbite, and PAH with their symptoms and quality of life. Individual reactions to the drug may, however, differ, so it is crucial to go over the advantages and disadvantages with a healthcare professional.

What Are the Things to Inform the Doctor Before Taking Iloprost Injection?

Before obtaining an injection of Iloprost for an allowed purpose, one should let the doctor know about:

• Have any allergies, particularly to Iloprost or related drugs?

• All of the prescription, over-the-counter, vitamin, and herbal supplement medications are used. By doing this, possible medication interactions are avoided.

• The medical background, especially if about kidney, lung, or cardiac issues.

• Whether they intend to get pregnant, are already nursing, or are pregnant. In some circumstances, Iloprost might not be appropriate.

How Is Iloprost Injection Administered?

• Check for particles within the vial before using it. Use caution if there are foreign particles present or if the solution seems discolored or hazy.

• An infusion pump is used to deliver a loprost injection intravenously through a peripheral line or peripherally implanted central catheter.

• Make use of an infusion set that has a 0.22- or 0.2-micron in-line filter.

• Iloprost should be delivered using an infusion pump capable of supporting both the minimum and maximum flow rates once it has been diluted.

• Iloprost administration requires the following from the infusion pump:

  • Rates 0.1 to 99.9 mL (milliliters) per hour.

  • 0.1 mL per hour rate adjustments.

  • Accuracy within five percent of the set rate.

  • Positive pressure-driven (continuous or pulsatile).

• The infusion line set and reservoir have to be composed of polyvinyl chloride.

• Prevent giving a medication bolus by accident. It is imperative to remove any leftover medication from the catheter system before flushing the catheter.

• Discard any leftover quantity.

What Are the Side Effects of Iloprost Injection?

Iloprost injectable side effects are possible, just with any drug. Typical adverse effects include the following:

• Headache.

• Flushing (sensation of warmth, redness, or tingling).

• Vomiting and nausea.

• Tightness or discomfort in the jaw.

• Hypotension or low blood pressure (dizziness or lightheadedness).

• Breathlessness.

• Diarrhea.

• Palpitation

Dietary Considerations:

When using Iloprost injections for permitted purposes, there are usually no particular dietary restrictions. However, depending on the general health and underlying medical condition, a doctor may suggest specific dietary changes.

Missed Dose:

Do not inject twice as much Iloprost to make up for missing a dosage for a prescribed use. It is imperative to speak with the physician to get advice on the next steps.

Overdose:

There have not been any documented cases of intravenous Iloprost overdoses. Diarrhea, vomiting, and hypotension are possible. There is no known particular counteragent. It is advised to interrupt the infusion session and to take monitoring and symptomatic treatments.

Storage

Iloprost injections are normally kept in a clinical or hospital environment in accordance with established procedures. In the rare event that Iloprost is prescribed for use at home, make sure to handle and store it according to the doctor's recommendations. This might entail refrigeration or the need for a certain temperature.

For Doctors:

Indication:

• Iloprost is a prostacyclin mimic that is prescribed to individuals with severe frostbite in order to lower their risk of amputation of their digits. The efficacy was demonstrated in young, healthy people who had high-altitude frostbite.

• Adults with pulmonary arterial hypertension (PAH) are also treated with Iloprost injections. High blood pressure in the arteries supplying blood to the lungs is a hallmark of PAH, a chronic illness. This may result in weariness, trouble breathing, and other symptoms.

Dose:

• Start the intravenous infusion at 0.5 ng/kg/minute (nanograms per kilogram per minute) and titrate up to a maximum of two ng/kg/minute in increments of 0.5 ng/kg/minute, dependent on tolerability at 30-minute intervals.

• Give a continuous infusion for six hours every day for a maximum of eight days in a row.

• In patients with moderate to severe liver impairment, start the infusion at 0.25 ng/kg/minute and titrate according to the previously mentioned instructions.

• Individuals with impaired kidney function should start an infusion at 0.5 ng/kg/minute and titrate. A lower dosage of 0.25 ng/kg/minute may be administered if the patient is unable to tolerate the initial 0.5 ng/kg/minute.

Dosing Considerations:

For authorized usage, keep the following points in mind while determining the appropriate injectable dose of Iloprost:

• Administration: In a hospital environment, a healthcare provider will inject Iloprost intravenously (by vein).

• Frequency: Depending on the patient and treatment plan, the frequency of administration may change. Usually, it is given numerous times a day while awake.

• Monitoring: Throughout the Iloprost injectable treatment, careful observation of blood pressure and other vital indicators is necessary.

• Individualization: To maximize therapy benefits and reduce adverse effects, each patient's dosage and administration regimen will be customized.

What Are the Pharmacological Aspects of Iloprost Injection?

• Pharmacodynamics:

Iloprost mimics the actions of prostacyclin PGI2, a powerful vasodilator and platelet aggregation inhibitor that occurs naturally. The smooth muscle cells in the walls of blood vessels are the main target of Iloprost. Iloprost relaxes these smooth muscle cells by attaching itself to certain receptors.

• Mechanism:

Iloprost functions similarly to prostacyclin, a chemical that is found in the body naturally. Prostacyclin has several important impacts. An artificial version of prostacyclin PGI2 is called Iloprost. Iloprost is a vasodilator, meaning it expands and relaxes blood vessels while also preventing platelet aggregation.

• Pharmacokinetics

  • General: The pharmacokinetics of intravenous Iloprost are linear in the dosage range of one to three ng/kg/min.

  • Half-Life: Iloprost has a half-life of 20 to 30 minutes.

  • Distribution and Absorption: In healthy participants, the apparent steady-state volume of distribution after intravenous infusion was 0.7 to 0.8 L/kg (liters per kilogram of body weight). In the range of 30 to 3000 pg/mL (picograms per milliliter), Iloprost is around sixty percent protein-bound, mostly to albumin, and this ratio is concentration-independent.

  • Excretion and Metabolism: Studies conducted in vitro show that cytochrome P450-dependent metabolism is not very important for the biotransformation of Iloprost. The main mechanism of Iloprost metabolism is through the carboxyl side chain's β-oxidation. Tetranor-iloprost, the primary metabolite, is present in the urine in both free and conjugated forms. In healthy individuals, clearance was around 20 mL/min/kg.

Toxicity:

• Acute Toxicity: Severe hypotension (low blood pressure), headache, dizziness, and trouble breathing might result from an Iloprost overdose. In these situations, immediate medical intervention is essential.

• Chronic Toxicity: Because Iloprost inhibits platelet aggregation, prolonged use of the medication may raise the risk of bleeding. It is important to monitor it on a regular basis.

Clinical Studies:

This study looked at how well Iloprost injection (IV) lowers the chance of digit amputation in cases of acute frostbite. RCT (Randomized control trial) with open-label intervention

Forty-seven individuals with acute frostbite (fingers or toes) were included.

Groups for Treatment:

• Group A: Usual care (Buflomedil, Aspirin).

• Group B: Six hours a day, up to eight days, of Iloprost injectable.

• Group C: Iloprost with recombinant tissue plasminogen activator (same regimen as B).

Findings:

• Amputation risk was estimated by a bone scan (BS2) on day seven.

• In comparison to conventional care (A), Iloprost groups (B & C) had considerably decreased BS2 anomalies.

• The results of the bone scan were validated by amputation follow-up data (available for 40 individuals).

Conclusion: Patients with severe frostbite may benefit from a lower risk of amputation as Iloprost therapy dramatically decreases the likelihood of abnormalities on bone scans.

What Are the Contraindications of Iloprost Injection?

Not everyone is a good candidate for Iloprost injection. Here are several important warning signs:

• Proven hypersensitivity to Iloprost or related drugs.

• Iloprost may exacerbate a patient's already extremely low blood pressure.

• If having an acute myocardial infarction or heart attack within the previous six months, there is a higher risk of problems with Iloprost.

• Severe, uncontrolled arrhythmias.

• Suspected pulmonary venous hypertension.

• During pregnancy and breastfeeding, Iloprost may damage the growing fetus or inadvertently enter breast milk, putting the baby in danger.

Warnings and Precautions:

• Systemic vasodilators like Iloprost have the potential to produce symptomatic hypotension. Accurately lower blood pressure before taking Iloprost. Keep an eye on the vital signs when using Iloprost.

• While using Iloprost, think about temporarily stopping any concurrent vasodilators or other antihypertensive drugs to lessen the possibility of additive hypotensive effects. If hypotension does not improve after stopping other antihypertensives and doing fluid resuscitation, think about decreasing the dosage or stopping Iloprost.

What Are the Drug Interactions of Iloprost Injection?

The interactions listed below may not be exhaustive; they have been chosen based on their possible importance. It is not advised to take this medication with any of the following medications. It is possible that the doctor will not prescribe this drug or will adjust some of the other medications used.

Here is a list of possible medication interactions with Iloprost injectable (for approved usage) based on previously acquired data:

• Medication That Inhibits Platelet Aggregation or Anticoagulants: The blood can have its effects enhanced by Iloprost. Bleeding risk may rise as a result. For example, consider:

• Blood thinners such as Dabigatran, Warfarin, and Aspirin.

• NSAIDs or nonsteroidal anti-inflammatory medicines such as Naproxen or Ibuprofen.

• Enhanced Effect of Hypotension: When used with other drugs that have a comparable effect, Iloprost can further reduce blood pressure. This may cause lightheadedness, dizziness, or even fainting. Examples include antihypertensives (drugs that lower blood pressure) and nitrates (a treatment for angina).

Specific Considerations:

• Being Pregnant: There is insufficient information to evaluate the risk of miscarriage, birth abnormalities, or other issues for expectant mothers using Iloprost. Further study is necessary. However, limited data indicate that there may not be an increased risk of negative consequences when utilized in the second and third trimesters.

• Nursing: Iloprost may damage the baby when it enters the breast milk. It is suggested that women using Iloprost should not breastfeed.

• Children: In youngsters, efficacy and safety have not been shown.

• Kidney and Liver Diseases: Individuals who have issues with their liver or kidneys may require dose modifications.