Metreleptin is a recombinant analog of human leptin, a hormone produced by adipocytes (fat cells) that plays a role in regulating food intake, energy expenditure, and body weight. Leptin acts primarily in the brain, particularly in the hypothalamus, to reduce hunger and promote satiety.

A synthetic analog of leptin called metreleptin (Myalept) is primarily used to treat individuals with lipodystrophy.

Metreleptin (Myalept) Uses:

• Lipodystrophy:
  • In addition to nutrition, it is used as a replacement treatment in individuals with congenital or acquired lipodystrophy to alleviate the side effects of leptin deficit.
• Limitations of use:
  • Not recommended for people with lipodystrophy linked to HIV
  • Patients with metabolic disorders (such as diabetes mellitus or hypertriglyceridemia) who do not also have congenital or acquired widespread lipodystrophy are not supposed to take it.

Metreleptin Dose in Adults: 

Metreleptin (Myalept) Dose in Lipodystrophy:

• Baseline Weight ≤40 kg (for people who weigh 40 kilograms or less):
  • Start with an initial dose of 0.06 mg of Metreleptin per kilogram of body weight once a day.
  • Depending on how well it works and whether there are any side effects, you can increase or decrease the dose by 0.02 mg per kilogram each day.
  • The maximum dose you can take in a day is 0.13 mg per kilogram of body weight.
• Baseline Weight >40 kg (for people who weigh more than 40 kilograms):
  • For males, start with an initial dose of 2.5 mg of Metreleptin once a day.
  • For females, start with an initial dose of 5 mg of Metreleptin once a day.
  • Like before, you can adjust the dose based on how well it's working and any side effects. You can increase or decrease it by 1.25 to 2.5 mg each day.
  • The highest daily dose allowed is 10 mg.
• Discontinuation:
  • If you need to stop taking Metreleptin and you have a higher risk of pancreatitis (inflammation of the pancreas) or very high triglyceride levels, you should gradually reduce the dose over a period of one week.
  • During this time, your doctor will keep an eye on your triglyceride levels and may also adjust your other medications for managing high lipids (fats in your blood) as needed.

These dosing instructions are flexible and can be adjusted based on how well the treatment is working for you and any side effects you might experience.

Metreleptin Dose in Children:

Metreleptin (Myalept) Dose in Lipodystrophy:

Age Consideration:

• Even though the manufacturer says Metreleptin can be used in infants, in most studies, patients were at least 6 months old. The youngest patients in some trials were at least 1 year old.

Dosage Based on Weight and Gender:

• For those weighing 40 kg or less (both boys and girls):
  • Start with a dose of 0.06 mg for every kilogram they weigh, given once a day.
  • If needed, adjust the dose up or down by 0.02 mg for every kilogram based on how they react or if they experience side effects.
  • The highest dose they can take in a day is 0.13 mg for every kilogram they weigh.
• For those weighing more than 40 kg:
  • For girls: Start with 5 mg once a day. Depending on how they react, you can change the dose by 1.25 to 2.5 mg. The most they can take in a day is 10 mg.
  • For boys: Start with 2.5 mg once a day. Like girls, depending on their reaction, adjust the dose by 1.25 to 2.5 mg. The maximum daily dose is also 10 mg.

If you need to stop the medication:

• If the patient has a higher chance of getting pancreatitis (a condition where the pancreas becomes inflamed) or has very high fat levels in their blood (triglycerides), you should gradually lower the dose over a week. During this time, monitor the fat levels in their blood. You might also need to adjust or start other medications to manage these fat levels.

Pregnancy Risk Factor C

• There aren't many reports about using metreleptin during pregnancy.
• Pregnant women with lipodystrophy can face challenges like high blood pressure during pregnancy, diabetes, slowed baby growth, loss of the baby before birth, a larger than normal baby, or miscarriage.
• Studies in the lab suggest that metreleptin might affect how the uterus contracts during childbirth.
• Metreleptin can also help some women who didn't have their periods before to start having them again, which means they could get pregnant.
• There's a program to monitor women who take metreleptin while they're pregnant.

Use of metreleptin during lactation

• We don't know if metreleptin gets into breast milk, but the natural version of this medicine does.
• Because there's a chance it could harm a breastfeeding baby, the maker of the medicine suggests moms choose between stopping breastfeeding or stopping the medicine, based on how important the treatment is for the mom.

Dose in Kidney Disease:

The company that makes the medicine hasn't provided any special dosing instructions for people with kidney problems, because they haven't studied it in that situation.

Dose in Liver disease:

The manufacturer of the medicine hasn't given any specific dose changes for people with liver problems because they haven't studied it in that situation.

Side effects of Metreleptin (Myalept)

• Central Nervous System:
  • Exhaustion
  • Headache
  • Dizziness
  • Paresthesia
• Miscellaneous:
  • Fever
• Endocrine & Metabolic:
  • Weight Gain
  • Ovarian Cyst
  • Decreased Glucose Tolerance
  • Diabetes Mellitus
  • Hypoglycemia
  • Weight Loss
  • Increased Serum Triglycerides
• Gastrointestinal:
  • Pancreatitis
  • Nausea
  • Abdominal Pain
  • Diarrhea
• Dermatologic:
  • Urticaria
• Genitourinary:
  • Proteinuria
• Immunologic:
  • Immunogenicity
• Infection:
  • Severe Infection
• Hematologic & Oncologic:
  • Anemia
  • Elevated Glycosylated Hemoglobin
• Local:
  • Erythema At Injection Site
• Otic:
  • Otic Infection
• Neuromuscular & Skeletal:
  • Arthralgia
  • Back Pain
•  
• Respiratory:
  • Upper Respiratory Tract Infection

Contraindications to Metreleptin (Myalept):

• Hypersensitivity to metreleptin and any formulation ingredient (such as anaphylaxis, urticaria, or widespread skin rash).
• Congenital Leptin deficiency is not linked to general obesity.

Cautions and alerts

Antibody development: [US Boxed Warning]:

• Some people who take metreleptin develop antibodies against it.
• This means their body fights the medicine like it's an invader.
• This can stop both the medicine and the body's natural leptin from working properly.
• Some people have had serious infections or their medical conditions got worse because of this.
• If a patient gets a serious infection or the medicine doesn't seem to be working, they should be tested to see if they've developed these antibodies.

Hypersensitivity reactions

• Allergic reactions: Some people have had allergic reactions, like hives or rashes, after taking metreleptin.
• If this happens, patients should quickly see a doctor and talk about possibly stopping the medicine.

Lymphomas: [US Boxed Warning]

• Some people with a condition called acquired generalized lipodystrophy have developed a type of cancer called T-cell lymphoma, whether they took metreleptin or not.
• Before giving metreleptin to patients with this condition or blood abnormalities, think about the pros and cons.
• We don't know for sure if metreleptin causes this cancer.
• But, people with lipodystrophy often have immune system problems, and those problems can increase the chance of getting certain cancers, including lymphoma.

Autoimmune disorders:

• Some people have had worsening of certain immune-related diseases, like a type of liver problem and a kidney condition, while using metreleptin.
• These conditions can lead to severe kidney issues.
• But, we don't know for sure if metreleptin caused these problems.
• People with lipodystrophy often have immune system problems to start with.
• So, when thinking about giving metreleptin to patients with immune system diseases, weigh the good and bad sides of the treatment.

Pancreatitis

• For people with a higher chance of getting pancreatitis, like those who had it before or have very high fat levels in their blood, be careful when stopping metreleptin.
• Lower the dose gradually over a week and keep an eye on their blood fat levels.
• Look out for signs of pancreatitis.
• Think about starting or changing the dose of medicines that lower blood fats.

Metreleptin: Drug Interaction

Monitoring parameters:

Testing for Antibodies

• Check for antibodies against metreleptin in patients if:
  • They get severe infections.
  • The medicine doesn't seem to be working.

Blood Glucose Monitoring

• For patients also taking insulin or medicines that increase insulin:
  • Keep a close watch on their blood sugar levels.

When Reducing Dose for Certain Patients

• For patients with a higher risk of pancreatitis:
  • Keep an eye on their blood fat (triglyceride) levels.

How to administer Metreleptin (Myalept)?

• Where to Inject:
  • Stomach, thigh, or upper arm.
• When to Inject:
  • Once a day, at the same time every day.
  • Can be given regardless of meal times.
• Important Tips:
  • Change the injection spot every day to avoid skin problems.
  • If the dose is more than 1 mL, split it into 2 equal shots.

Mechanism of action of Metreleptin (Myalept):

• Metreleptin is a man-made version of the hormone leptin.
• It works by attaching to a specific receptor in the body called the leptin receptor.
• When it attaches, it triggers a pathway called JAK/STAT, which helps treat problems caused by not having enough leptin.
• It's used to treat issues related to a lack of leptin in people with a condition called generalized lipodystrophy.

Distribution:

• The medicine spreads in an area about 4-5 times bigger than the volume of your blood.

Metabolism:

• The body doesn't seem to break down the medicine much once it's inside.

How long it lasts:

• The medicine stays in the body for about 4 hours before half of it is gone.

When it's strongest:

• The medicine reaches its highest level in the body about 4 hours after taking it, but this can vary between 2 to 8 hours.

Getting rid of the medicine:

• The kidneys mainly remove the medicine. If there are antibodies against the medicine or if the kidneys aren't working well, it might take longer to clear out of the system.

International Brand Names of Metreleptin:

• Myalept

Metreleptin Brand Names in Pakistan:

Not Available.