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Lutathera (Lutetium Lu-177 dotatate) - Uses, Dose, MOA, Side effects

Lutetium Lu-177 dotatate is a radiopharmaceutical used in nuclear medicine for the treatment of certain neuroendocrine tumors. It is also known by its brand name, "Lutathera." Lutetium Lu-177 dotatate is a targeted radionuclide therapy, meaning it delivers radiation directly to the tumor cells.

Lutathera (Lutetium Lu-177 dotatate) is a radiolabeled somatostatin analog that destroys somatostatin receptor-positive cells by emitting beta and gamma radiations.

Lutetium Lu-177 dotatate Uses:

Gastroenteropancreatic neuroendocrine tumors:
- It is indicated for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in adults, including foregut, midgut, and hindgut neuroendocrine tumors.

Lutathera (Lutetium Lu-177 dotatate) Dose in Adults:

Note: Premedications and concomitant medications need to be given.

Lutathera (Lutetium Lu-177 dotatate) Dose in the treatment of Gastroenteropancreatic neuroendocrine tumors:

Dose:

You'll get a dose of 7.4 GBq (200 mCi) through an IV. This will happen once every 8 weeks, and you'll get it 4 times in total.

Medications to Take Before and With the Treatment:

Somatostatin Medications:
- Stop taking the long-lasting kind (like long-acting octreotide) 4 weeks before starting the treatment.
- You can take the short-acting kind if needed, but stop it 24 hours before the treatment.
- After each Lutetium treatment, get a shot of long-acting octreotide 30 mg between 4 to 24 hours later.
- Don't take the long-lasting kind within 4 weeks before the next Lutetium dose.
- You can continue with the long-acting octreotide shot every 4 weeks after finishing all Lutetium doses, and keep this up for up to 18 months or until your condition changes.
For Nausea:
- Take a medicine for nausea 30 minutes before the amino acid solution.
Amino Acid Solution:
- Start getting an IV with amino acids 30 minutes before the Lutetium dose. This solution has special ingredients in it (L-lysine and L-arginine) and will keep going during and for 3 hours after the Lutetium dose.
- Even if your Lutetium dose changes, the amino acid dose stays the same.

Use in Children:

Not indicated.

Pregnancy Risk Category: N

Lutetium Lu 177 dotatate could harm a baby if taken during pregnancy.
Before starting the treatment, check if you are pregnant.
Women who can become pregnant should use birth control during the treatment and for 7 months after the last dose.
Men who are with women who can become pregnant should also use birth control during the treatment and for 4 months after the last dose.
The radiation from the treatment might cause both men and women to become infertile. This might be for a short time or forever.

Lutetium Lu-177 dotatate use during breastfeeding:

We don't know if this medication is in breast milk.
Since it could be risky for a breastfed baby, the company suggests not breastfeeding during the treatment and for 2.5 months after the last dose.

Dose in Kidney Disease:

Lutetium Lu 177 dotatate and Kidney Function:

First, you'll be using a formula called the Cockcroft-Gault equation to figure out how well your kidneys are working, using your actual body weight.

Before Starting Treatment:

If your kidneys clear 30 mL or more per minute (CrCl ≥30 mL/minute), you can take the regular dose. However, you should keep a closer eye on how your kidneys are doing since there might be a higher chance of side effects.
If your kidneys clear less than 30 mL per minute (CrCl <30 mL/minute) or if you have end-stage kidney disease: There's no specific advice from the manufacturer about how to adjust the dose, because it hasn't been tested.

If Kidney Problems Occur During Treatment:

If your kidneys clear less than 40 mL per minute (CrCl <40 mL/minute), or there's a 40% rise in your creatinine (a kidney test) from when you started, or a 40% drop in how well your kidneys are clearing: You should stop taking lutetium Lu 177 dotatate until things get back to normal. Once they do, restart the treatment at a half dose (3.7 GBq or 100 mCi). If your kidneys handle this reduced dose well, you can go back to the regular dose (7.4 GBq or 200 mCi) for the next treatment. If you keep having kidney problems, or if you had to pause the treatment for 16 weeks or more because of them, you should stop taking lutetium Lu 177 dotatate for good.

Dose in Liver Disease:

Before starting treatment:

If your liver is slightly or moderately impaired, you don't need to change the dose of the medication.
If your liver is severely impaired (bilirubin is more than 3 times the normal upper limit and any AST level), the manufacturer's instructions do not provide specific dose adjustments because this situation hasn't been studied.

During treatment:

If your bilirubin level goes higher than 3 times the normal upper limit (grade 3 or 4) or if your albumin is less than 30 g/L and your prothrombin ratio is less than 70%, you should stop taking lutetium Lu 177 dotatate until your liver problem completely gets better.
Once your liver issue is resolved, you can start taking the medication again, but at a lower dose of 3.7 GBq (100 mCi). If this lower dose doesn't cause liver problems, you can go back to the regular dose of 7.4 GBq (200 mCi) for the next treatment.
If your liver problem is severe and requires a treatment delay of more than 16 weeks, or if it keeps happening again, you will have to stop taking lutetium Lu 177 dotatate permanently.

Common Side Effects of Lutathera (Lutetium Lu-177 dotatate):

Cardiovascular:
- Peripheral Edema
- Flushing
- Hypertension
Central Nervous System:
- Fatigue
- Dizziness
- Headache
- Anxiety
Dermatologic:
- Alopecia
Endocrine & Metabolic:
- Hyperglycemia
- Increased Gamma-Glutamyl Transferase
- Hyperuricemia
- Hypocalcemia
- Hypokalemia
- Hyperkalemia
- Hypernatremia
- Hypoglycemia
Gastrointestinal:
- Nausea
- Vomiting
- Abdominal Pain
- Diarrhea
- Decreased Appetite
Hematologic & Oncologic:
- Lymphocytopenia
- Anemia
- Leukopenia
- Thrombocytopenia
- Neutropenia
Hepatic:
- Increased Serum Alkaline Phosphatase
- Increased Serum AST
- Increased Serum ALT
- Increased Serum Bilirubin
Neuromuscular & Skeletal:
- Back Pain
- Limb Pain
Renal:
- Increased Serum Creatinine
- Renal Failure
Respiratory:
- Cough

Less Common Side Effects of Lutathera (Lutetium Lu-177 dotatate):

Cardiovascular:
- Atrial fibrillation
Gastrointestinal:
- Constipation
- Dysgeusia
Genitourinary:
- Urotoxicity
Neuromuscular & skeletal:
- Myalgia
- Neck pain
Miscellaneous:
- Fever

Contraindications to Lutathera (Lutetium Lu-177 dotatate):

The manufacturer's labeling does not list any specific situations where you should absolutely avoid using the medication (contraindications).

Warnings and precautions

Suppression of bone marrow

During treatment with lutetium Lu 177 dotatate, some people may experience a drop in their blood cell counts, which can lead to conditions like anemia, low platelet levels, and reduced white blood cell count.
This happened more often in patients receiving this treatment compared to long-acting octreotide.
In a study, the lowest point in platelet levels occurred about 5.1 weeks after the first dose of lutetium Lu 177 dotatate.
Fortunately, most patients who developed low platelet levels got better, with their platelet levels returning to normal within about 2 months.
It's important to regularly check your blood counts while on this treatment and your doctor may need to adjust the therapy, pause it, or even stop it if necessary.

Gastrointestinal toxicity:

When taking lutetium Lu 177 dotatate, you might experience gastrointestinal issues like nausea, vomiting, diarrhea, and abdominal pain, which are often not very severe (grade 1 or 2).

Hepatotoxicity:

While using lutetium Lu 177 dotatate, some people may experience liver-related problems.
These can include rare conditions like liver tumor bleeding, swelling, or tissue damage, as well as congestion and bile flow issues in the liver.
If you have liver metastases, there may be a higher risk of liver problems because of the radiation from this treatment.

The neuroendocrine hormonal crisis

In rare cases, after taking lutetium Lu 177 dotatate, some people may experience a neuroendocrine hormonal crisis.
This can cause symptoms like flushing, diarrhea, difficulty breathing, and low blood pressure.
These reactions usually happen during or within a day after the first dose.
Some patients might also experience high levels of calcium in the blood (hypercalcemia).

Toxicity in the renal system:

Using lutetium Lu 177 dotatate can sometimes lead to kidney problems, including kidney failure.
In one study, kidney failure occurred anywhere from 3 to 36 months after receiving the treatment.
Some patients who developed kidney issues had existing kidney problems or other risk factors like diabetes or high blood pressure.
To help protect the kidneys, a specific amino acid solution is given alongside the lutetium Lu 177 dotatate treatment before, during, and after.
It's important not to lower the dose of this amino acid solution even if the lutetium Lu 177 dotatate dose is reduced.
Patients should also be encouraged to urinate regularly during and after the treatment.

Secondary malignancies

In some clinical trials, a small number of patients who received lutetium Lu 177 dotatate developed myelodysplastic syndrome (MDS) and leukemia, which are both types of blood-related cancers.
The time it took for these conditions to develop varied, with a median of about 28 months for MDS and 55 months for leukemia.
It's important to be aware that long-term exposure to radiation, like that from this treatment, can increase the risk of developing cancer.

Renal impairment

If you already have mild or moderate kidney problems before taking lutetium Lu 177 dotatate, you may have a higher risk of kidney issues with this treatment.
To keep a close eye on your kidney function, your healthcare provider will monitor your renal health more frequently.
They'll do this by checking your serum creatinine levels and calculated creatinine clearance.
It's important to note that lutetium Lu 177 dotatate hasn't been studied in patients with severe kidney impairment, so its safety and effectiveness in this group are uncertain.

Lutetium Lu-177 dotatate: Drug Interaction

Risk Factor D (Consider therapy modification)

Somatostatin Analogs

May diminish the therapeutic effect of Lutetium Lu 177 Dotatate. Specifically, the therapeutic effect of Lutetium Lu 177 Dotatate may be diminished if the timing of Somatostatin Analog administration is not carried out as recommended. Management: Discontinue long-acting somatostatin analogs at least 4 weeks and short-acting octreotide at least 24 hours prior to each lutetium Lu 177 dotatate dose. Administer short- and long-acting octreotide during treatment as recommended. See full monograph.

Monitoring parameters:

Blood Cell Counts:

Keep track of your blood cell levels.
Pay attention to any signs of anemia, low platelets, or low white blood cells.

Kidney Function:

Monitor your kidney health.
Regularly check your serum creatinine and creatinine clearance.
Be more vigilant if you already have kidney issues.

Liver Health:

Keep an eye on your liver function.
Check levels of transaminases, bilirubin, and albumin.

Pregnancy Status:

Verify if female patients of childbearing age are pregnant before starting the treatment.

Neuroendocrine Hormonal Crisis:

Watch for signs like flushing, diarrhea, difficulty breathing, and low blood pressure.
These symptoms can indicate a hormonal crisis.

Secondary Malignancies:

Be aware that myelodysplastic syndrome and leukemia (blood-related cancers) have been reported in some patients.

How to administer Lutathera (Lutetium Lu-177 dotatate)?

IV Infusion:

Administer it as an IV infusion over a period of 30 to 40 minutes.
Do not give it as an IV bolus (rapid injection).

Needle Insertion and Connection:

Insert a 2.5 cm, 20-gauge needle (short needle) into the lutetium Lu 177 dotatate vial.
Connect this short needle to a catheter leading to a 500 mL sterile normal saline (NS) solution.
Make sure the short needle does not touch the lutetium Lu 177 dotatate solution in the vial and is not connected to the patient.
Do not allow NS to flow into the lutetium Lu 177 dotatate vial before the infusion begins, and don't mix the lutetium Lu 177 dotatate directly into the NS solution.

Long Needle Insertion:

Insert a separate 9 cm, 18-gauge (long needle) into the lutetium Lu 177 dotatate vial.
Ensure that the long needle touches and is secured to the bottom of the vial during the entire infusion.
Connect the long needle to the patient through an IV catheter prefilled with sterile NS solution meant for the lutetium Lu 177 dotatate infusion.

Flow Regulation:

Use a clamp or pump to control the flow of the NS solution via the short needle into the lutetium Lu 177 dotatate vial.
The flow rate should be 50 to 100 mL/hour for 5 to 10 minutes, then increased to 200 to 300 mL/hour for an additional 25 to 30 minutes.
The NS solution, entering the vial through the short needle, will carry the lutetium Lu 177 dotatate from the vial to the patient, completing the infusion in 30 to 40 minutes.

Monitoring:

Keep an eye on the vial's solution level during the infusion.
Once the radioactivity level is stable for at least 5 minutes, disconnect the vial from the long needle line and clamp the saline line.
After the infusion is done, flush the line with 25 mL of normal saline (NS).

Antiemetics:

Give antiemetic (anti-nausea) medications to the patient 30 minutes before the amino acid solution.

Amino Acid Solution:

Use a three-way valve to administer the amino acid solution using the same venous access as the lutetium Lu 177 dotatate infusion.
Alternatively, administer the amino acid solution through a separate venous access in the patient's other arm.
Continue the amino acid infusion during the lutetium Lu 177 dotatate infusion and for at least 3 hours after it's completed.

Mechanism of action of Lutathera (Lutetium Lu-177 dotatate):

Lutetium Lu 177 dotatate is a radioactive substance that gives off beta and gamma radiation.
It has the ability to attach to specific receptors called somatostatin receptors, with the highest affinity for subtype 2 receptors (SSRT2).
When it binds to cells that express somatostatin, the lutetium Lu 177 dotatate is taken inside these cells.
The beta radiation it emits can cause damage to these somatostatin receptor-positive cells and the nearby cells by creating harmful free radicals.

Distribution:

Lutetium Lu 177 dotatate is distributed throughout the body, with a total distribution volume of 460 liters.
Within four hours after administration, it moves into the kidneys, tumor sites, liver, spleen, and in some patients, the pituitary gland and thyroid.
Its ability to penetrate tissues is limited, with a maximum depth of 2.2 mm (average penetration: 0.67 mm).

Protein Binding:

The non-radioactive form of lutetium dotatate binds to plasma proteins at a rate of 43%.

Half-life Elimination:

The average time it takes for lutetium Lu 177 dotatate to be eliminated from the bloodstream is approximately 71 hours, with some variation (± 28 hours).

Excretion:

Most of lutetium Lu 177 dotatate is removed from the body through the urine.
Although elimination in the urine may take some time, more than 99% of the lutetium Lu 177 dotatate is expected to be eliminated within 14 days after it's administered.

International Brand Names of Lutetium Lu-177 dotatate:

Lutathera

Lutetium Lu-177 dotatate Brand Names in Pakistan:

No Brands Available in Pakistan.