Peginesatide - Its Use in Chronic Kidney Disease With Anemia

Overview:

Recombinant human erythropoietin changed how anemia was treated for those with chronic kidney disease (CKD). To bypass the costly genetic method of creating this medicine, scientists developed Peginesatide, a chemically made alternative that boosted red blood cell production. In 2012, the Food and Drug Administration (FDA) of the United States approved Peginesatide for the use of this drug. Unlike other treatments, Peginesatide had its own benefits, such as reduced immune issues, less frequent dosing, and affordability. Doctors prescribed it for dialysis CKD patients. However, Peginesatide triggered more heart problems in non-dialysis CKD patients than a similar drug, Darbepoetin, leading to its withdrawal due to unexplained severe adverse reactions.

Indications:

Peginesatide is used to treat a condition called anemia in adults who have kidney disease and need dialysis.

Contraindications:

• Individuals with uncontrolled high blood pressure.

• Individuals with severe allergic reactions to Peginesatide, which could include a dangerous reaction called anaphylaxis.

Limitations of Use:

• Peginesatide should not be used in patients with kidney disease who are not on dialysis due to safety concerns.

• It is also not recommended for people with cancer-related anemia, as it is not known if it is safe and helpful in that situation.

• It should not be used instead of blood transfusions when quick anemia correction is needed.

• Peginesatide has not been proven to make people feel better or improve their daily lives.

Drug Recommendation:

• Pregnancy Category C: If pregnant, the decision to use this medicine should be carefully considered based on potential benefits versus risks to the baby.

• Breastfeeding: It is unclear if this medicine passes into human milk. Since some medicines do, using this medicine while breastfeeding should be done cautiously.

• Pediatric Use: Check with the doctor whether this medicine is safe or effective for children.

• Geriatric Use: Older patients do not seem to have different responses compared to younger patients in terms of safety and effectiveness.

Precautions and Warnings:

• Heart Problems: Raising hemoglobin levels above eleven grams (g) per deciLiter (dL) can increase the risk of serious heart issues.

• Heart Attacks and Strokes: Higher hemoglobin levels are linked to a greater chance of heart attacks and strokes.

• Heart Failure: Trying to push hemoglobin levels too high can lead to heart failure.

• Blood Clotting: Drugs that increase hemoglobin beyond eleven g/dL can cause blood clots in dialysis access and other clot-related problems.

• No Extra Benefits: There is no added advantage in raising hemoglobin levels above eleven g/dL; it is risky.

• Existing Heart or Stroke Issues: Patients with heart or stroke problems are particularly at risk when aiming for high hemoglobin levels.

• Poor Drug Response: Kidney disease patients who do not respond well to these drugs are at even higher risk of heart problems and death.

• Rapid Hemoglobin Increase: Increasing hemoglobin by more than one g/dL in two weeks raises risks.

• Cancer Patients: Similar risks were found in cancer patients who received these drugs.

• Heart Surgery: These drugs have been associated with a higher risk of death in heart surgery patients.

• Orthopedic Procedures: Patients undergoing orthopedic surgeries while on these drugs face a greater risk of deep vein blood clots.

Adverse Drug Effects:

• Higher Risk of Death, Heart Attack, Stroke, and Blood Clots: Using Peginesatide to raise hemoglobin levels beyond a certain point could lead to increased chances of these severe issues.

• High Blood Pressure: Peginesatide drugs can cause hypertension (high blood pressure).

• Severe Allergic Reactions: Serious allergic reactions to this drug are possible

For Patients

What Is Peginesatide?

Peginesatide is a prescription medicine that acts like a natural protein called erythropoietin. It is used to treat a condition called anemia, which is when a person has very few red blood cells in adults who have chronic kidney disease and are on dialysis. Peginesatide helps the body's bone marrow create more red blood cells, which increases the hemoglobin level. However, if the hemoglobin level becomes too high or increases too quickly, it can lead to serious health issues, even potentially fatal ones. These problems can occur even if one takes Peginesatide without a noticeable increase in the hemoglobin level.

How Should a Person Use Peginesatide?

• One should get the blood pressure checked as the healthcare provider suggests.

• The healthcare provider will perform blood tests to monitor the hemoglobin and iron levels before and during the Peginesatide treatment.

• Peginesatide is given once a month either into the vein through the dialysis access or under the skin.

• A healthcare professional will usually administer Peginesatide. In some situations, the healthcare provider might teach the caregiver how to do the injections at home.

If a person is trained to do the injections at home:

• Follow the healthcare provider's instructions closely.

• Read and understand the "Instructions for Use" that come with Peginesatide.

• Use Peginesatide just as the healthcare provider has directed. Do not change the dose unless they inform them to change it.

• The healthcare provider will show the caregiver how much Peginesatide to use, how to inject it, how often, and how to dispose of used containers, needles, and syringes safely.

• If a person misses a dose, contact the healthcare provider promptly for guidance.

• If a person accidentally injects more Peginesatide than prescribed, get in touch with the healthcare provider right away for advice.

When Peginesatide Should Not Be Used?

• If a person has chronic kidney disease but is not on dialysis.

• If a person has anemia due to cancer treatment and not because of chronic kidney disease.

• As a substitute for emergency treatment for anemia, like getting a blood transfusion.

• Using Peginesatide has not been proven to make one feel better, less tired, or improve overall well-being. It is uncertain whether Peginesatide is safe and effective for children.

• If a person had a severe allergic reaction to Pegnisesatide in the past.

• If high blood pressure is not properly maintained, then Peginesatide should not be used.

What Are the Possible Side Effects of Peginesatide?

1. High blood pressure is a common issue in people with kidney disease who take Peginesatide. It could make the blood pressure higher or harder to control, even if a person did not have high blood pressure before. The doctor will monitor the blood pressure and might adjust the blood pressure medicine.

2. Serious allergic reactions could cause symptoms like:

• Dizziness.

• Trouble breathing.

• Chest tightness.

• Swelling in the face or body.

• All-over itching.

If this happens, stop Peginesatide and get medical help.

3. A body could create antibodies against Peginesatide. These might make it hard for the body to make red blood cells, leading to severe anemia. Contact the doctor if a person feels super tired, dizzy, or faint.

4. Common side effects of Peginesatide are:

• Shortness of breath.

• Headache.

• Diarrhea.

• Pain in joints, back, legs, or arms.

• Nausea.

• Low blood pressure (hypotension).

• Vomiting.

• Fever.

• Cough.

• Higher potassium levels in the blood.

• Issues with hemodialysis access.

• Upper respiratory infections.

For Doctors

Pharmacodynamics:

• Effect on Blood: Peginesatide causes the body to produce more young red blood cells (reticulocytes), eventually increasing hemoglobin levels. The speed at which hemoglobin levels rise can differ among individuals and is influenced by the Peginesatide dose given.

• Effect on Heart Repolarization: The impact of giving a dose of Peginesatide (0.1 mg per kilogram of body weight through an IV) on the time it takes for the heart to reset between beats (QTc interval) was studied in healthy volunteers. It was found that this dose did not delay the heart's repolarization process compared to a placebo. Although this dose represents the average dose used in phase three trials, it might not fully represent doses higher than 0.1 milligrams (mg) per kilogram (kg) in the target patients.

Pharmacokinetics:

Peginesatide attaches to and activates a special receptor in our body that helps produce red blood cells. This activation process happens in lab tests with cells that turn into red blood cells. Peginesatide uses a pathway in the body that is like a communication system, which results in more of these young red blood cell precursors being made. When people take Peginesatide under the skin, its levels in the blood go up the most after about two days. Peginesatide's availability in the body after this type of injection is around forty-six percent. It leaves the body mostly through urine and stays in the body for about forty-eight hours after it is put into the vein in dialysis patients. Peginesatide behaves the same way in people with kidney disease on dialysis, no matter their age, gender, or race. The chance of Peginesatide interacting with other drugs in the body is very low. This medicine causes an increase in new red blood cells first, followed by a rise in hemoglobin, the part of the blood that carries oxygen. The speed of this rise in hemoglobin can be different for each person and depends on how much peginesatide they took.

Drug Interactions:

Peginesatide does not attach itself to certain proteins found in the blood. This medicine does not influence most enzymes in the liver that process drugs.

Adverse Drug Effects:

1. Allergic reactions may manifest as:

• Urticaria.

• Respiratory distress.

• Facial or throat swelling.

• Vertigo.

2. Cardiovascular manifestations could include:

• Angina.

• Brachial pain.

• Abrupt paresthesias or paralysis.

• Intense cephalalgia.

• Cognitive impairment.

• Visual and auditory disturbances.

• Arrhythmias.

• Syncope.

3. Respiratory distress might present as:

• Wheezing.

• Coughing.

• Tachypnea.

• Hemoptysis.

4. Venous thromboembolic events could lead to:

• Limb pain.

• Edema.

• Erythema.

• Ecchymosis.

• Hemorrhagic tendencies.

• Purpura.

5. Neurological symptoms might encompass:

• Seizures.

• Hypertensive urgency.

• Anxious states.

• Acute severe headaches.

Less severe potential side effects of Peginesatide encompass:

• Gastrointestinal distress, including diarrhea, nausea, and vomiting.

• Musculoskeletal discomforts like back pain, coughing, muscle spasms, headaches, and joint pain.

Severe manifestations such as:

• Sudden visual impairments.

• Cardiovascular irregularities.

• Profound neurological symptoms.

Dosage and Administration:

• Iron Check and Causes of Anemia: Before and during treatment with Peginesatide, doctors need to check if the patient has enough iron and look for other reasons for anemia (like vitamin problems, inflammation, or bleeding).

• Patients With Kidney Disease: The dose of Peginesatide is personalized, and doctors use the smallest amount, which reduces the need for blood transfusions. Using other drugs that boost red blood cells (erythropoiesis-stimulating agents or ESAs) to reach a hemoglobin level higher than eleven g/dL (a measure of blood's ability to carry oxygen) can lead to more risks like heart issues. There is no specific hemoglobin level that is safe, so doctors and patients need to balance the sound effects of fewer transfusions with the higher risks of heart problems.

• Starting Treatment: Peginesatide treatment begins when the hemoglobin level is less than ten g/dL. The starting dose for patients who have not received ESAs before is 0.04 mg for every kilogram of their body weight, given as a single injection every month.

• Switching From Other Treatments: If an individual was getting other ESAs before, the starting dose of Peginesatide is based on the dose they were taking each week. Doctors adjust the starting dose according to a table. The way the patient receives the injection (under the skin or into a vein) stays the same.

Monitoring and Adjustments: Doctors check a person’s hemoglobin levels every two weeks until they stabilize, and then at least once a month. The dose might be reduced if the hemoglobin level changes too quickly or goes too high. If the level is close to eleven g/dL or higher, the dose could be lowered or stopped for a while. If their response to Peginesatide isn't good after a while, the dose might be increased, but if it still doesn't work well, the treatment could be stopped.

Missed Doses: If a person misses a dose, they should take it as soon as possible and return to the regular monthly schedule.

Preparation and Administration: Peginesatide comes in different types of packaging. Use single-use vials and pre-filled syringes only once. Store unused parts in the fridge. Protect Peginesatide from light and check for anything unusual before using it. Do not mix it with other drugs, and make sure there is no sign of damage to the packaging.

Available Doses in the Form of Vials:

1. Single-Use Vials (No Preservatives):

• 2 mg in 0.5 milliliter (mL).

• 3 mg in 0.5 mL.

• 4 mg in 0.5 mL.

• 5 mg in 0.5 mL.

• 6 mg in 0.5 mL.

2. Single-Use Pre-Filled Syringes (No Preservatives):

• 1 mg in 0.5 mL.

• 2 mg in 0.5 mL.

• 3 mg in 0.5 mL.

• 4 mg in 0.5 mL.

• 5 mg in 0.5 mL.

• 6 mg in 0.5 mL.

3. Multiple-Use Vials (With Preservatives):

• 10 mg in 1 mL.

• 20 mg in 2 mL.

Overdose:

Taking too much Peginesatide can cause hemoglobin levels to go higher than they should. If this happens, doctors may stop or lower the Peginesatide dose and, if needed, remove some blood (phlebotomy) to help manage it. Overdosing on similar drugs has also led to severe high blood pressure.

Toxicology:

• Carcinogenic Effects and Reproduction: Peginesatide at doses up to 0.25 mg/kg for rats was given every three weeks through an Intravenous (IV) and did not cause cancer. This dose is about fourteen percent of what humans receive at a dose of 0.35 mg/kg in dialysis patients. Similarly, in a twenty-six-week study in mice, Peginesatide at doses of 0.1, 0.25, or 0.5 mg/kg every three weeks did not lead to cancer. Peginesatide did not cause genetic mutations or chromosomal damage in various tests.

• Effect on Fertility: In rats, when male and female rats were given Peginesatide at weekly intervals before and during mating, fertility was reduced at doses of 0.1 mg/kg (about five percent of the dose given to patients) and more so at doses of 1.0 mg/kg or higher. Males experienced reduced weight of reproductive organs, and females had fewer viable fetuses at 0.1 mg/kg or higher. This effect seemed to be due to losses before and after implantation, and it did not seem to affect their reproductive cycles.