pegfilgrastim subcutaneous: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing

Aching or pain in the bones and muscles may occur. Taking a non-aspirin pain reliever such as acetaminophen may help relieve pain. Ask your doctor or pharmacist for more details. Redness, swelling, itching, or bruising at the injection site may also occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: pink/bloody urine, easy bleeding/bruising, fever, fast heartbeat, purple or red spots on your skin, back pain.

Get medical help right away if you have any very serious side effects, including: breathing problems (such as trouble breathing, shortness of breath, fast breathing), unusual decrease in urination, unusual tiredness, swelling/puffiness of the body.

Rarely, serious (possibly fatal) damage to the spleen may occur. Get medical help right away if you develop stomach/abdominal pain or shoulder pain.

Rarely, this medication may increase the risk of developing a certain bone marrow disorder (myelodysplastic syndrome-MDS) or blood cancer (acute myeloid leukemia-AML) in people with breast or lung cancer who are receiving chemotherapy/radiation. Ask your doctor for more details.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US –

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.

In Canada – Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Pegfilgrastim – an overview | ScienceDirect Topics

17.6.1 Polymeric Nanoparticles

Polymeric NPs are widely employed across the majority of nanomedicine applications. As their synthesis process is relatively simple they are considered the simplest forms of NPs. In 2013, in the United States, two of the drugs within the top 10 bestsellers were polymeric drugs (Neulasta and Copaxone) (Duncan, 2014). Polymeric nanomedicines are mainly classified into two categories, that is, degradable polymeric systems and polymer–drug conjugates.

Polymer–drug conjugates are mostly designed for different purposes other than degradable polymers. As these conjugates increase the drug’s bioavailability and half-life along with their degradability, they are most beneficial in controlled release applications. The applications of polymers in nanomaterials are wide and various depending on the desired therapeutic outcomes. The simplest polymeric nanomedicine is the use of single polymer chains as they work as therapeutic agents or modifying agents for diagnostic agents and drugs. Copaxone (glatiramer acetate) is an example of a copolymer composed of l-alanine, l-glutamic acid, l-tyrosine, and l-lysine (Johnson et al., 1998; Tarhini et al., 2017).

Copaxone was approved in 1996 as an immunomodulatory agent for multiple sclerosis patients. In general, hydrophilic polymers are attached to drug molecules to improve solubility, biocompatibility, and increase their circulation (Alconcel et al., 2011). For instance, poly(ethylene glycol) is one of the most popular polymers, and has been applied to several drugs such as Neulasta, which got FDA approval in 2002.

Neulasta is considered a very successful drug for the treatment of chemotherapy-induced neutropenia. PEGylation of granulocyte colony stimulating factor has increased the biological half-life of Neulasta by almost fivefold (Benbrook, 2015).

In 2014, Plegridy, a PEGylated interferon gamma beta-1a, received FDA approval and has been used for multiple sclerosis treatment. Proteins attached to PEG have shown both better exposure and biological half-life as compared with therapeutic proteins alone (Hu et al., 2012). As compared with other INF-based treatments of multiple sclerosis, Plegridy has the advantage of having a much longer half-life. Thus, making the treatment less frequently administered, that is, only once every 2–4 weeks.

Another example is Adynovate, a PEGylated factor VIII, was approved in 2015 for treating bleeding and to prevent the occurrence of bleeding episodes for patients with hemophilia A. Less frequent administration of factor VIII by using the PEGylated form may decrease the possibility of generating the formation of antifactor VIII antibody, which occurs in almost 30% of patients leading to decreased drug efficacy (Ing et al., 2016).

Aside from the advantages mentioned previously, polymer NPs can be helpful in improving the controlled release of drugs by using hydrophobic materials. The main concept is using the slow degradability of these materials to achieve kinetically driven release. For example, Eligard, a well-established polymeric NPs-based drug, is formed by incorporating leuprolide into PLGA NPs. It is considered an effective treatment in reducing prostate cancer symptoms (Berges, 2005; Weissig et al., 2014). PLGA slowly decomposes into a degradable polymer that provides the ability to control decomposition time. Camptothecin, a chemotherapeutic agent, has been encapsulated inside cyclodextrin-PEG copolymers. The resultant NPs (CRLX101) are administered by i.v. injection to promote the EPR effect and enhance targeting. CRLX101 shows promising results as it passed phase I and II clinical trials in patients suffering from peritoneal, ovarian, tubal, and rectal cancers (Clark et al., 2016; Svenson et al., 2011).

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Important Safety Information

Do not take Neulasta^® if you have had a serious allergic reaction to pegfilgrastim or filgrastim.

Before you receive Neulasta

^®, tell your healthcare provider about all of your healthcare conditions, including if you:

• Have a sickle cell disorder
• Have had severe skin reactions to acrylic adhesives
• Are allergic to latex – The needle cap on the prefilled syringe contains dry natural rubber (derived from latex).
• Have kidney problems
• Are pregnant or plan to become pregnant. It is not known if Neulasta^® may harm your unborn baby.
• Are breastfeeding or plan to breastfeed. It is not known if Neulasta^® passes into your breast milk.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

What are the possible serious side effects of Neulasta

^®?

• Spleen Rupture. Your spleen may become enlarged and can rupture while taking Neulasta^®. A ruptured spleen can cause death. Call your healthcare provider right away if you have pain in the left upper stomach area or left shoulder tip area.
• A serious lung problem called Acute Respiratory Distress Syndrome (ARDS). Call your healthcare provider or get emergency medical help right away if you have shortness of breath with or without a fever, trouble breathing, or a fast rate of breathing.
• Serious Allergic Reactions. Neulasta^® can cause serious allergic reactions. These reactions can cause a rash over your whole body, shortness of breath, wheezing, dizziness, swelling around your mouth or eyes, fast heart rate and sweating.

If you have an allergic reaction during the delivery of Neulasta^®, remove the on-body injector for Neulasta^® by grabbing the edge of the adhesive pad and peeling off the on-body injector. Get emergency medical help right away.

• Sickle Cell Crises. You may have a serious sickle cell crisis, which could lead to death, if you have a sickle cell disorder and receive Neulasta^®.
• Kidney injury (glomerulonephritis). Neulasta^® can cause kidney injury. Call your healthcare provider right away if you develop any of the following symptoms: swelling of your face or ankles, blood in your urine or dark colored urine, or you urinate less than usual.
• Increased white blood cell count (leukocytosis). Your healthcare provider will check your blood during treatment with Neulasta^®.
• Decreased platelet count (thrombocytopenia). Your healthcare provider will check your blood during treatment with Neulasta^®. Tell your healthcare provider if you have unusual bleeding or bruising during treatment with Neulasta^®. This could be a sign of decreased platelet counts, which may reduce the ability of your blood to clot.
• Capillary Leak Syndrome. Neulasta^® can cause fluid to leak from blood vessels into your body’s tissues. This condition is called “Capillary Leak Syndrome” (CLS). CLS can quickly cause you to have symptoms that may become life-threatening. Get emergency medical help right away if you develop any of the following symptoms:
• Swelling or puffiness and are urinating less than usual
• Trouble breathing
• Swelling of your stomach area (abdomen) and feeling of fullness
• Dizziness or feeling faint
• A general feeling of tiredness
• Myelodysplastic syndrome and acute myeloid leukemia. If you have breast cancer or lung cancer, when Neulasta^® is used with chemotherapy and radiation therapy, or with radiation therapy alone, you may have an increased risk of developing a precancerous blood condition called myelodysplastic syndrome (MDS) or a blood cancer called acute myeloid leukemia (AML). Symptoms may include tiredness, fever, and easy bruising or bleeding. Call your healthcare provider if you develop these symptoms during treatment with Neulasta^®.
• Inflammation of the aorta (aortitis). Inflammation of the aorta (the large blood vessel which transports blood from the heart to the body) has been reported in patients who received Neulasta^®. Symptoms may include fever, abdominal pain, feeling tired, and back pain. Call your healthcare provider if you experience these symptoms.

The most common side effect of Neulasta^® is pain in your bones and in your arms and legs.

These are not all the possible side effects of Neulasta^®. Call your healthcare provider for medical advice about side effects. You may report negative side effects to the FDA at 1-800-FDA-1088.

Please see Neulasta^® Patient Information.

Neulasta^® Injection: 6 mg/0.6 mL in a single-dose prefilled syringe for manual use only.

Neulasta^® Injection: 6 mg/0.6 mL in a single-dose prefilled syringe co-packaged with the on-body injector (OBI) for Neulasta^® (Neulasta^® Onpro^® kit).

Pegfilgrastim injection

What is this medicine?

PEGFILGRASTIM (PEG fil gra stim) is a long-acting granulocyte colony-stimulating factor that stimulates the growth of neutrophils, a type of white blood cell important in the body’s fight against infection. It is used to reduce the incidence of fever and infection in patients with certain types of cancer who are receiving chemotherapy that affects the bone marrow, and to increase survival after being exposed to high doses of radiation.

How should I use this medicine?

This medicine is for injection under the skin. If you get this medicine at home, you will be taught how to prepare and give the pre-filled syringe or how to use the On-body Injector. Refer to the patient Instructions for Use for detailed instructions. Use exactly as directed. Tell your healthcare provider immediately if you suspect that the On-body Injector may not have performed as intended or if you suspect the use of the On-body Injector resulted in a missed or partial dose.

It is important that you put your used needles and syringes in a special sharps container. Do not put them in a trash can. If you do not have a sharps container, call your pharmacist or healthcare provider to get one.

Talk to your pediatrician regarding the use of this medicine in children. While this drug may be prescribed for selected conditions, precautions do apply.

What side effects may I notice from receiving this medicine?

Side effects that you should report to your doctor or health care professional as soon as possible:

• allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue

• back pain

• dizziness

• fever

• pain, redness, or irritation at site where injected

• pinpoint red spots on the skin

• red or dark-brown urine

• shortness of breath or breathing problems

• stomach or side pain, or pain at the shoulder

• swelling

• tiredness

• trouble passing urine or change in the amount of urine

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):

What may interact with this medicine?

Interactions have not been studied.

Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

What if I miss a dose?

It is important not to miss your dose. Call your doctor or health care professional if you miss your dose. If you miss a dose due to an On-body Injector failure or leakage, a new dose should be administered as soon as possible using a single prefilled syringe for manual use.

Where should I keep my medicine?

Keep out of the reach of children.

If you are using this medicine at home, you will be instructed on how to store it. Throw away any unused medicine after the expiration date on the label.

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:

• kidney disease

• latex allergy

• ongoing radiation therapy

• sickle cell disease

• skin reactions to acrylic adhesives (On-Body Injector only)

• an unusual or allergic reaction to pegfilgrastim, filgrastim, other medicines, foods, dyes, or preservatives

• pregnant or trying to get pregnant

• breast-feeding

What should I watch for while using this medicine?

You may need blood work done while you are taking this medicine.

If you are going to need a MRI, CT scan, or other procedure, tell your doctor that you are using this medicine (On-Body Injector only).

Home – UDENYCA®

UDENYCA^®, a biosimilar treatment, is a man-made form of granulocyte colony-stimulating factor (G-CSF). G-CSF is a substance produced by the body. It stimulates the growth of neutrophils, a type of white blood cell important in the body’s fight against infection.

Source: UDENYCA^® (pegfilgrastim-cbqv) package insert. Redwood City, CA: Coherus BioSciences, Inc.; 2019.

Biosimilars are FDA-approved biologic medications that are as safe and effective as the original biologics (known as the reference product). Biosimilars have no clinically meaningful differences from the reference product. This means that there is no compromise in safety and effectiveness of the biosimilar when compared to the reference product. Biosimilars introduce competition into the marketplace and can lower the cost of cancer-related treatment.

Source: Biosimilar and interchangeable products. US Food and Drug Administration. Updated October 23, 2017. Accessed May 12, 2020. https://www.fda.gov/drugs/biosimilars/biosimilar-and-interchangeable-products#nodiff

Chemotherapy works by targeting cancerous cells. It can also affect and lower healthy cell counts, including the white blood cells that fight infections.

Source: Tai E, Guy GP, Dunbar A, Richardson LC. Cost of cancer-related neutropenia or fever hospitalizations, United States, 2012. J Oncol Pract. 2017;13(6):e552-e561.

Do not take UDENYCA^® if you have had a serious allergic reaction to human G-CSFs such as pegfilgrastim or filgrastim products.

Source: UDENYCA^® (pegfilgrastim-cbqv) package insert. Redwood City, CA: Coherus BioSciences, Inc.; 2019.

Before you receive UDENYCA^®, tell your healthcare provider about all of your medical conditions, including if you have a sickle cell disorder, have kidney problems, are pregnant or plan to become pregnant (it is not known if UDENYCA^® will harm your unborn baby), are breastfeeding or plan to breastfeed (it is not known if UDENYCA^® passes into your breast milk).

Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Source: UDENYCA^® (pegfilgrastim-cbqv) package insert. Redwood City, CA: Coherus BioSciences, Inc.; 2019.

The most common side effects of UDENYCA^® are pain in the bones, arms, and legs. These are not all the possible side effects of UDENYCA^®. Talk with your doctor about managing bone pain and any other side effects. Be sure to review the Patient Information for more side effect information.

Source: UDENYCA^® (pegfilgrastim-cbqv) package insert. Redwood City, CA: Coherus BioSciences, Inc.; 2019.

UDENYCA^® is given as an injection under your skin (subcutaneous injection) by a healthcare provider the day after chemotherapy treatment.

Source: UDENYCA^® (pegfilgrastim-cbqv) package insert. Redwood City, CA: Coherus BioSciences, Inc.; 2019.

You will need to return to your healthcare provider the day after chemotherapy to receive UDENYCA^®. It’s important to not miss this appointment, so discuss any transportation questions you may have with your healthcare team prior to treatment.

Side effects, dosage, uses, and more

Neulasta is a brand-name prescription medication. It’s FDA-approved for the following*:

• Reducing the risk of infection due to a condition called febrile neutropenia in people with non-myeloid cancers. To use Neulasta, you must be taking an anti-cancer drug that could cause febrile neutropenia (low level of white blood cells called neutrophils).
• Treating radiation sickness. The type of radiation sickness that Neulasta is used for is called hematopoietic subsyndrome.

Neulasta drug class and forms

Neulasta contains one active drug ingredient: pegfilgrastim. Neulasta belongs to a drug class called leukocyte growth factors. A drug class is a group of medications that work in a similar way.

Neulasta comes in two forms. One is a single-dose prefilled syringe. This form is given the day after you have chemotherapy as a subcutaneous injection (an injection directly under your skin).

A healthcare provider will give you the Neulasta injection, or you may be able to give yourself the injection at home after being trained. The syringe is available in one strength: 6 mg/0.6 mL.

The second form is called Neulasta Onpro, which is an on-body injector (OBI). A healthcare provider will apply it to your stomach or the back of your arm the same day you receive chemotherapy.

Neulasta Onpro delivers a dose of the drug about a day after the OBI is applied. This means you don’t have to return to your doctor’s office for an injection. Neulasta Onpro is available in one strength: 6 mg/0.6 mL.

Note: While the Neulasta syringe can be used to treat both conditions listed above, Neulasta Onpro isn’t used to treat radiation sickness.

*For detailed information on these conditions, see the “Neulasta uses” section.

Effectiveness

For information on the effectiveness of Neulasta, see the “Neulasta uses” section below.

Neulasta is available as a brand-name medication. Neulasta has three biosimilar versions: Fulphila, Udenyca, and Ziextenzo.

A biosimilar is a drug that’s similar to a brand-name medication. A generic drug, on the other hand, is an exact copy of the active ingredient in a brand-name medication.

Biosimilars are based on biologic drugs, which are created from parts of living organisms. Generics are based on regular medications made from chemicals. Biosimilars and generics also tend to cost less than brand-name drugs.

Neulasta contains one active drug ingredient: pegfilgrastim. This means pegfilgrastim is the ingredient that makes Neulasta work.

Neulasta can cause mild or serious side effects. The following lists contain some of the key side effects that may occur while taking Neulasta. These lists don’t include all possible side effects.

For more information on the possible side effects of Neulasta, talk with your doctor or pharmacist. They can give you tips on how to deal with any side effects that may be bothersome.

Note: The Food and Drug Administration (FDA) tracks side effects of drugs they have approved. If you would like to report to the FDA a side effect you’ve had with Neulasta, you can do so through MedWatch.

Mild side effects

The mild side effects of Neulasta can include:

• bone pain (more information in “Side effect details” below)
• pain in your arms or legs

Most of these side effects may go away within a few days or a couple of weeks. But if they become more severe or don’t go away, talk with your doctor or pharmacist.

Serious side effects

Serious side effects from Neulasta aren’t common, but they can occur. Call your doctor right away if you have serious side effects. Call 911 if your symptoms feel life threatening or if you think you’re having a medical emergency.

Serious side effects and their symptoms can include:

• Aortitis (inflammation of the aorta, the main artery of the heart). Symptoms can include:
  • malaise (feelings of discomfort or uneasiness)

Other serious side effects, explained in more detail below in “Side effect details,” include:

Side effect details

You may wonder how often certain side effects occur with this drug. Here’s some detail on some of the side effects that may occur with either the Neulasta shot or patch.

Allergic reaction

As with most drugs, some people can have an allergic reaction after taking Neulasta. It’s not known how many people had an allergic reaction to Neulasta in clinical trials. But most reactions occurred in people who received a dose of Neulasta for the first time.

And in some people, the reaction occurred again days later, after the treatment for the allergic reaction was stopped. An acrylic adhesive is used with the Neulasta on-body injector (OBI) and can cause an allergic reaction if someone has an allergy to adhesives.

Symptoms of a mild allergic reaction can include:

• skin rash
• itchiness
• flushing (warmth and redness in your skin)

A more severe allergic reaction is rare but possible. Symptoms of a severe allergic reaction can include:

• swelling under your skin, typically in your eyelids, lips, hands, or feet
• swelling of your tongue, mouth, or throat
• trouble breathing

Call your doctor right away if you have a severe allergic reaction to Neulasta. Call 911 if your symptoms feel life threatening or if you think you’re having a medical emergency.

Bone pain

Bone pain is a common side effect of Neulasta. In clinical studies, 31% of people who took Neulasta reported bone pain compared with 26% of people who took a placebo (treatment with no active drug).

It’s not known exactly why Neulasta causes bone pain in some people. One theory involves histamine, a protein that your immune system makes to help fight infections.

Neulasta stimulates your immune system into producing more white blood cells, which also leads to more histamine being created. And the release of histamine has been linked to bone marrow swelling and pain. But more research is needed before it’s known for sure why Neulasta causes bone pain.

If you have bone pain while using Neulasta, tell your doctor. They may prescribe a medication for the pain, such as ibuprofen or naproxen. Or they may switch you to a medication other than Neulasta.

Acute respiratory distress syndrome (ARDS)

Acute respiratory distress syndrome (ARDS) is a possible side effect of Neulasta, but it rarely occurs. ARDS wasn’t reported during clinical trials of the drug, but the condition has been reported in a few people taking Neulasta since it came on the market.

With ARDS, your lungs become filled with fluid and can’t deliver enough oxygen to the rest of your body. This could lead to other lung problems such as pneumonia or infections.

Symptoms of ARDS can include:

ARDS is a potentially life-threatening condition that requires prompt medical care. If you’re taking Neulasta and you have trouble breathing, a fast rate of breathing, or shortness of breath, call 911 or go to the emergency room.

Capillary leak syndrome

Capillary leak syndrome is a rare but serious potential side effect of Neulasta. It’s not known for sure how often it occurred in clinical studies.

Capillaries are tiny blood vessels. Capillary leak syndrome occurs when fluids and proteins manage to leak out of capillaries and into surrounding body tissue. This can cause low blood pressure and hypoalbuminemia (low levels of an important protein called albumin).

Symptoms of capillary leak syndrome can include:

As mentioned above, capillary leak syndrome is rare, but it can be fatal. So if you think you have symptoms of capillary leak syndrome while taking Neulasta, call 911 or go to the emergency room.

Glomerulonephritis

Although glomerulonephritis wasn’t reported in clinical studies of Neulasta, it’s been reported in people who took the drug since it came on the market.

Glomerulonephritis refers to inflammation (swelling) of the glomeruli, which are clusters of blood vessels in your kidneys. Glomeruli help filter waste products from your blood and pass them into urine.

Symptoms of glomerulonephritis can include:

• bloating and swelling due to fluid retention, especially in the face, feet, hands, or stomach
• high blood pressure
• urine that’s pink or dark brown in color
• urine that looks foamy

If you think you have glomerulonephritis while taking Neulasta, tell your doctor. They may reduce your dose, which usually clears up glomerulonephritis. But if that doesn’t work, your doctor will likely have you stop taking Neulasta. They may have you try a different medication instead.

Leukocytosis

Leukocytosis is a rare but potentially serious side effect of Neulasta.

In clinical studies, leukocytosis occurred in less than 1% of people who took the drug. Neulasta was compared with a placebo, but it’s not known whether or how often leukocytosis occurred in people who took placebo. No complications related to leukocytosis were reported in these studies.

Leukocytosis is a condition in which the level of white blood cells called leukocytes is higher than normal. This is usually a sign that your body is trying to fight an infection. However, leukocytosis can also be a sign of leukemia (a cancer that affects the bone marrow or blood).

Symptoms of leukocytosis can include:

• bleeding or bruising
• breathing problems such as wheezing
• fever

Because you’re at an increased risk for infection while taking Neulasta, tell your doctor right away if you develop a fever or other symptoms of leukocytosis. They’ll help determine the cause and what treatment is right for you.

Ruptured spleen

An enlarged spleen and a ruptured spleen weren’t reported in clinical trials of Neulasta. However, these conditions have been reported in people who took Neulasta since the drug came on the market.

The spleen is an organ that’s in the upper left of your belly, under your ribs. It works to filter blood and fight infection.

Symptoms of a ruptured spleen can include:

• confusion
• feeling anxious or restless
• lightheadedness
• nausea
• pain in the upper left area of the belly
• pale skin
• shoulder pain

A ruptured spleen is a life threatening condition requiring prompt medical care. If you’re taking Neulasta and have pain in your left shoulder or upper left belly area, tell your doctor right away.

Fever (not a side effect)

Fever isn’t an expected side effect of taking Neulasta.

Developing a fever during your Neulasta treatment may mean you have an infection. Fever can also be a symptom of rare but serious side effects of Neulasta, such as acute respiratory distress syndrome (ARDS), aortitis, or leukocytosis. (For more about ARDS and leukocytosis, see those sections below.)

If you develop a fever while taking Neulasta, tell your doctor right away. They can help determine what’s causing your fever and the best way to treat it.

The Neulasta dosage your doctor prescribes will depend on several factors. These include:

• the type and severity of the condition you’re using Neulasta to treat
• your age
• the form of Neulasta you take
• other medical conditions you may have

Typically, your doctor will start you on a low dosage. Then they’ll adjust it over time to reach the amount that’s right for you. Your doctor will ultimately prescribe the smallest dosage that provides the desired effect.

The following information describes dosages that are commonly used or recommended. However, be sure to take the dosage your doctor prescribes for you. Your doctor will determine the best dosage to fit your needs.

Drug forms and strengths

Neulasta comes in two forms. One is a single-dose prefilled syringe. This form is given the day after you have chemotherapy as a subcutaneous injection (an injection directly under your skin).

A healthcare provider will give you the Neulasta injection, or you may be able to give yourself the injection at home after being trained. The syringe is available in one strength: 6 mg/0.6 mL.

The second form is called Neulasta Onpro, which is an on-body injector (OBI). A healthcare provider will apply it to your stomach or the back of your arm the same day you receive chemotherapy.

Neulasta Onpro delivers a dose of the drug about a day after the OBI is applied. This means you don’t have to return to your doctor’s office for an injection. Neulasta Onpro is available in one strength: 6 mg/0.6 mL.

It’s important to note that Neulasta Onpro isn’t used to treat radiation sickness.

Dosage for preventing infections during chemotherapy

For preventing infection during chemotherapy, Neulasta is given as a single dose once each chemotherapy cycle. A single dose is either one injection with the syringe or the use of one Neulasta Onpro.

You shouldn’t use Neulasta either 14 days before or 24 hours after having chemotherapy.

Dosage for radiation sickness

For treating hematopoietic subsyndrome of acute radiation syndrome (radiation sickness), Neulasta is given as two doses. You’ll have them 1 week apart. A single dose is one injection with the syringe.

Pediatric dosage

Neulasta is approved to help prevent infections in children receiving chemotherapy. The drug is also approved for use in children with radiation sickness. There are no age-based restrictions for using Neulasta.

For Neulasta dosages in children who weigh more 99 pounds (45 kg), see the dosage sections above.

Dosages for children who weigh less than 99 pounds (45 kg) are based on weight. Your child’s doctor will determine what Neulasta dosage is right for your child.

What if I miss a dose?

If you miss giving yourself an injection of Neulasta with a syringe, call your doctor as soon as you realize this. They can advise you on when you take your dose.

If you miss an appointment for a Neulasta injection, call your doctor’s office. The staff can reschedule you and adjust the timing of future visits, if necessary.

It’s also possible to miss a dose while using Neulasta Onpro. This is because the on-body injector can sometimes fail to work or leak. If this happens, call your doctor’s office right away. The staff will schedule a time for you to come in for a Neulasta injection so that you receive your full dose.

To help make sure that you don’t miss a dose, try setting a reminder on your phone. You can also write your treatment schedule in a calendar.

Will I need to use this drug long term?

Neulasta is meant to be used as a long-term treatment, so long as you’re receiving chemotherapy. If you and your doctor determine that Neulasta is safe and effective for you, you’ll likely take it long term.

Here are answers to some frequently asked questions about Neulasta.

Can Claritin help me manage side effects of Neulasta?

Possibly. Neulasta works by triggering your immune system to make more white blood cells.

Certain proteins called histamines are also released by this process. It’s not exactly known why the release of histamines leads to side effects such as bone pain. But research has shown that histamine is involved in inflammation, which can cause pain.

Claritin is an antihistamine medication. It works by blocking the action of histamine. By doing so, Claritin may help reduce bone pain in people taking Neulasta, but more research is needed.

If you’re taking Neulasta and having bone pain, talk with your doctor. They can review available treatments and help determine which one is best for you.

How long do side effects of the Neulasta shot last?

It’s not known because there isn’t enough data on how long side effects of the Neulasta shot last.

In clinical studies, some people reported bone pain or pain in their arms or legs after receiving Neulasta. But the researchers didn’t record how long the side effects lasted.

For more details on potential side effects of Neulasta, please refer to the “Neulasta side effects” section above. You can also reach out to your doctor.

How long does Neulasta stay in your system?

The timing can vary. Clinical studies showed that clearing Neulasta from the body is affected by your body weight and the number of neutrophils (a type of white blood cell) present in your blood.

In general, after one injection, Neulasta is completely eliminated from your system within 14 days.

When I fly, do I need to tell airport security that I have Neulasta Onpro?

Yes. The manufacturer of Neulasta has a Transportation Security Administration (TSA) notification card that you can print and present to security personnel at the airport. Click here to access the card.

However, it’s recommended that you avoid traveling (including driving) during the 26- to 29-hour window after you receive Neulasta Onpro. The device is dispensing the drug into your body during this time. And traveling may increase the risk of Neulasta Onpro getting knocked off your body.

If you have questions about your Neulasta treatment while traveling, talk with your doctor.

Why do I have to keep Neulasta Onpro away from cellphones and other electrical devices?

The signals from these electrical devices may interfere with Neulasta Onpro and keep it from providing your dose.

It’s recommended that you keep Neulasta Onpro at least 4 inches away from electrical devices, including cell phones and microwaves.

If you have questions about using Neulasta Onpro, ask your doctor.

How should I dispose of Neulasta Onpro?

After you’ve received your full dose of Neulasta by using Neulasta Onpro, you should dispose of the device by putting it in a Sharps container.

The manufacturer of Neulasta has a Sharps Disposal Container Program to help you safely dispose of Neulasta Onpro. This is offered at no additional cost to you. You can click here to sign up for the program (see the “Injector Disposal Program” section), or call 1-844-696-3852.

The Food and Drug Administration (FDA) approves prescription drugs such as Neulasta to treat certain conditions. Neulasta may also be used off-label for other conditions. Off-label use is when a drug that’s approved to treat one condition is used to treat a different condition.

Neulasta for preventing infections during chemotherapy

Chemotherapy is a type of cancer treatment that uses medications to kill dividing cancer cells. This helps prevent cancer from growing and spreading.

However, chemotherapy isn’t specific for cancer cells. Chemotherapy also destroys other dividing cells in the body, including helpful cells such as white blood cells.

Neutropenia is a blood condition in which neutrophil levels become low. Neutrophils are a type of white blood cell that protect your body from infection. If your neutrophil levels are low, your body won’t be able to properly fight off bacteria. So having neutropenia increases your risk for infection.

Febrile neutropenia occurs when you have neutropenia and develop a fever, which can be a sign of an infection. And having neutropenia means that you can’t fight infections as well as usual. So febrile neutropenia is a serious condition that a doctor should check out right away.

What Neulasta does

Neulasta is used to help prevent infection in people with certain cancers who are receiving chemotherapy. The cancers are called non-myeloid cancers, which don’t involve bone marrow (the tissue inside bones that makes blood cells). An example of a non-myeloid cancer is breast cancer.

Neulasta aids you in creating more neutrophils and other white blood cells. This helps your body be more prepared to fight infections, help prevent febrile neutropenia, and shorten how long you have neutropenia.

Effectiveness

In clinical studies, Neulasta has been shown to decrease both the risk of febrile neutropenia and how long the condition lasts in people who do develop it.

One study compared Neulasta with filgrastim (Neupogen), which is another drug proven to help prevent and treat febrile neutropenia. Researchers wanted to see if Neulasta was as effective as filgrastim at shortening how long febrile neutropenia lasts.

In this study, people received a chemotherapy regimen (treatment plan) consisting of doxorubicin and docetaxel every 21 days. Similar regimens have been linked to severe neutropenia that occurred in all cases.

The condition lasted around 5 to 7 days on average, and about 30% to 40% of people developed febrile neutropenia.

The people were randomly assigned to receive either Neulasta or filgrastim. The researchers found that Neulasta was similarly effective as filgrastim.

People who received Neulasta and developed severe neutropenia had the condition for an average of 1.8 days. People who received filgrastim and developed severe neutropenia had the condition for an average of 1.7 days.

A second study with an identical setup also found similar results. People who received Neulasta and developed severe neutropenia had the condition for an average of 1.7 days. This was compared with an average of 1.6 days in people who received filgrastim.

Neulasta for radiation sickness

Neulasta is also approved by the FDA to treat radiation sickness. The condition may also be referred to as acute radiation syndrome or radiation toxicity.

The type of radiation sickness that Neulasta is used for is called hematopoietic subsyndrome. The amounts of radiation exposure that cause this syndrome are described as myelosuppressive, meaning they lead your bone marrow to make fewer blood cells.

Radiation sickness occurs when a person is exposed to high doses of radiation over a very short period of time (typically only a few minutes). High doses of radiation can kill the cells in your body. Radiation sickness can be fatal if the radiation exposure is severe enough.

For ethical reasons, researchers weren’t able to test Neulasta’s ability to treat radiation sickness in people. Instead, the drug was approved to treat radiation sickness based on animal studies, in addition to the data mentioned in the “Neulasta for preventing infections during chemotherapy” section above.

Note: Neulasta Onpro (the Neulasta on-body injector) shouldn’t be used to treat radiation sickness.

Off-label uses for Neulasta

In addition to the uses listed above, Neulasta may be used off-label in certain cases. Off-label drug use is when a drug that’s approved for one use is used for a different one that’s not approved.

Post-hematopoietic cell transplants

Neulasta isn’t FDA-approved for use post-hematopoietic cell transplant (HCT). However, the drug may be used off-label for this purpose.

An HCT is a procedure that’s performed after you’ve had chemotherapy. Once chemotherapy is used to kill cancer cells, stem cells are transplanted to you during an HCT. This is done because chemotherapy doesn’t just attack cancer cells. It can also kill stem cells made by your bone marrow.

Stem cells normally become platelets (blood cells that help your blood clot), red blood cells, and white blood cells, which are all vital in keeping you alive.

When an HCT is given to people with blood cancers, an infection can occur. This is because the new cells aren’t fully effective right after the transplant.

Using Neulasta after an HCT helps your body make new white blood cells, including neutrophils. A healthy level of neutrophils helps your body fight off infection better.

Effectiveness

Although Neulasta isn’t FDA-approved for use after an HCT, clinical studies have shown the drug is effective for this use.

One study compared Neulasta with a similar drug, filgrastim (Neupogen), which is FDA-approved to be used after an HCT. Neulasta is given as just a single injection, while filgrastim is given as multiple injections on several days.

In the study, 14 people with non-Hodgkin lymphoma, multiple myeloma, or amyloidosis received Neulasta after having an HCT.

The researchers compared the results of these people with the results of people who received filgrastim in the past. This means that there wasn’t a placebo group (treatment with no active drug).

The researchers found that it took an average of about 11 days for neutrophils to return to safe levels in people who received Neulasta. In comparison, it took an average of 14 days for people who took filgrastim in the past.

If you have questions about taking Neulasta after an HCT, talk with your doctor.

Neulasta and children

Neulasta is approved to help prevent infections in children receiving chemotherapy. The drug is also approved for use in children with radiation sickness. There are no age-based restrictions for using Neulasta.

Neulasta is typically used with other drugs. This is because Neulasta is only one part of a cancer treatment regimen (plan).

Neulasta is commonly used with chemotherapy because Neulasta helps prevent or treat side effects of chemotherapy.

Commonly used chemotherapy drugs include:

• bleomycin
• carboplatin
• cyclophosphamide
• docetaxel (Taxotere)
• doxorubicin (Doxil)
• gemcitabine (Gemzar)
• paclitaxel

Keep in mind that this is not a full list of chemotherapy medications. Talk with your doctor if you have questions about any chemotherapy drugs and whether Neulasta might benefit you.

Other drugs are available that can treat your condition. Some may be a better fit for you than others. If you’re interested in finding an alternative to Neulasta, talk with your doctor. They can tell you about other medications that may work well for you.

Note: Some of the drugs listed below are used off-label to treat these specific conditions. Off-label use is when a drug that’s approved to treat one condition is used to treat a different condition.

Alternatives for preventing infections during chemotherapy

Examples of other drugs that may be used to help prevent infections during chemotherapy include:

• tbo-filgrastim (Granix)
• pegfilgrastim (Fulphila)
• sargramostim (Leukine)
• filgrastim (Neupogen)
• filgrastim-aafi (Nivestym)
• pegfilgrastim-cbqv (Udenyca)
• filgrastim-sndz (Zarxio)
• pegfilgrastim-bmez (Ziextenzo)

Alternatives for radiation sickness

Examples of other drugs that may be used to treat radiation sickness include:

• tbo-filgrastim (Granix)
• potassium iodide
• Prussian blue
• pegfilgrastim (Fulphila)
• filgrastim (Neupogen)
• filgrastim-aafi (Nivestym)
• pegfilgrastim-cbqv (Udenyca)
• filgrastim-sndz (Zarxio)
• pegfilgrastim-bmez (Ziextenzo)

You may wonder how Neulasta compares with other medications that are prescribed for similar uses. Here we look at how Neulasta and Granix are alike and different.

Ingredients

Neulasta contains the active drug pegfilgrastim. Granix contains the active drug tbo-filgrastim.

Both pegfilgrastim and tbo-filgrastim belong to a class of medications known as granulocyte-colony stimulating factors (G-CSFs). A medication class is a group of drugs that work in a similar way.

A G-CSF is a medication that causes neutrophils (a type of white blood cell) to grow in your bone marrow. Bone marrow is the tissue inside bones that makes blood cells. G-CSFs are man-made copies of the G-CSF hormone your body makes naturally.

Uses

Both Neulasta and Granix are approved by the Food and Drug Administration (FDA) to reduce the risk of infection due to a condition called febrile neutropenia in people with non-myeloid cancers.* To use these medications, you must be taking an anti-cancer drug that could cause febrile neutropenia.

Neulasta is also FDA-approved to treat radiation sickness. * The type of radiation sickness that Neulasta is used for is called hematopoietic subsyndrome.

*For detailed information on these conditions, see the “Neulasta uses” section.

Drug forms and administration

Here’s some information about the forms of Neulasta and Granix and how they’re given.

Neulasta forms

Neulasta comes in two forms. One is a single-dose prefilled syringe. This form is given the day after you have chemotherapy as a subcutaneous injection (an injection directly under your skin).

A healthcare provider will give you the Neulasta injection, or you may be able to give yourself the injection at home after being trained.

The second form is called Neulasta Onpro, which is an on-body injector (OBI). A healthcare provider will apply it to your stomach or the back of your arm the same day you receive chemotherapy.

Neulasta Onpro delivers a dose of the drug about a day after the OBI is applied. This means you don’t have to return to your doctor’s office for an injection.

Note: Neulasta Onpro isn’t used to treat radiation sickness.

Granix forms

Granix also comes in two forms: a single-dose prefilled syringe and a single-dose vial of liquid solution. Both forms can be given by a healthcare provider as an injection subcutaneously, directly under your skin. But with some training, you may be able to give yourself injections at home.

Dosage frequency

One important difference between Neulasta and Granix is how often the drugs are given to reduce the risk of infection during chemotherapy.

Neulasta is given only once during each chemotherapy cycle. Granix, on the other hand, is given every day until the levels of neutrophils in your blood return to normal.

Side effects and risks

Neulasta and Granix are both used to help prevent infections during chemotherapy. Therefore, these medications can cause some similar side effects, but some different ones as well. Below are examples of these side effects.

Mild side effects

These lists contain examples of mild side effects that can occur with Neulasta, with Granix, or with both drugs (when taken individually).

• Can occur with Neulasta:
• Can occur with Granix:
• Can occur with both Neulasta and Granix:

Serious side effects

These lists contain examples of serious side effects that can occur with Neulasta, with Granix, or with both drugs (when taken individually).

• Can occur with Neulasta:
• Can occur with Granix:
• Can occur with both Neulasta and Granix:
  • capillary leak syndrome (a condition in which tiny blood vessels leak)

Effectiveness

The only use both Neulasta and Granix are approved for is reducing the risk of infection due to a condition called febrile neutropenia in people with non-myeloid cancers.

Separate studies of the two drugs were compared in a larger review of studies called a systemic review. Researchers looked at data from 18 studies.

People had received pegfilgrastim (the active drug in Neulasta), filgrastim, or a similar drug, including Granix. The pegfilgrastim group was less likely to develop febrile neutropenia and less likely to require a hospital stay as a result of febrile neutropenia. This was compared with the other drug groups.

Costs

Neulasta and Granix are both brand-name drugs.

Neulasta has three biosimilar versions: Fulphila, Udenyca, and Ziextenzo.

Granix isn’t technically considered to be a biosimilar, according to the FDA.

A biosimilar is a drug that’s similar to a brand-name medication. A generic drug, on the other hand, is an exact copy of the active ingredient in a brand-name medication.

Biosimilars are based on biologic drugs, which are created from parts of living organisms. Generics are based on regular medications made from chemicals. Biosimilars and generics also tend to cost less than brand-name drugs.

According to estimates on GoodRx.com, Neulasta and Granix prices will vary depending on your prescribed dose. The actual price you’ll pay for either drug will depend on your insurance plan, your location, and the pharmacy you use.

Like Granix (discussed above), the drug Fulphila has uses similar to those of Neulasta. Here’s a comparison of how Neulasta and Fulphila are alike and different.

Ingredients

Neulasta and Fulphila contain the same active drug, pegfilgrastim.

Technically, Fulphila contains the active ingredient pegfilgrastim-jmdb. This is because Fulphila is a type of drug known as a biosimilar. A biosimilar is a drug that’s similar to a brand-name medication. Biosimilars are based on biologic drugs, which are created from parts of living organisms.

In this case, Neulasta is the biologic drug, and Fulphila is the biosimilar of it. Pegfilgrastim and pegfilgrastim-jmdb both work in the same way.

Pegfilgrastim belongs to a class of medications known as granulocyte-colony stimulating factors (G-CSFs). A class of medications is a group of drugs that work in a similar way.

A G-CSF is a medication that causes neutrophils (a type of white blood cell) to grow in your bone marrow. Bone marrow is the tissue inside bones that makes blood cells. And G-CSFs are man-made copies of the G-CSF hormone your body makes naturally.

Uses

Both Neulasta and Fulphila are approved by the Food and Drug Administration (FDA) to reduce the risk of infection due to a condition called febrile neutropenia in people with non-myeloid cancers.* To use these medications, you must be taking an anti-cancer drug that could cause febrile neutropenia.

Neulasta is also FDA-approved to treat radiation sickness.* The type of radiation sickness that Neulasta is used for is called hematopoietic subsyndrome.

Fulphila isn’t approved to help move blood cells from bone marrow into the blood for a hematopoietic cell transplant (HCT).

*For detailed information on these conditions, see the “Neulasta uses” section.

Drug forms and administration

Both Neulasta and Fulphila come as a single-dose prefilled syringe. This form is given the day after you have chemotherapy as a subcutaneous injection (an injection directly under your skin).

A healthcare provider will give you the Neulasta injection, or you may be able to give yourself the injection at home after being trained.

Neulasta also comes in another form called Neulasta Onpro, which is an on-body injector (OBI). A healthcare provider will apply it to your stomach or the back of your arm the same day you receive chemotherapy.

Neulasta Onpro delivers a dose of the drug about a day after the OBI is applied. This means you don’t have to return to your doctor’s office for an injection.

Note: Neulasta Onpro isn’t used to treat radiation sickness.

Side effects and risks

Neulasta and Fulphila both contain pegfilgrastim. Therefore, these medications can cause very similar side effects. Below are examples of these side effects.

Mild side effects

This list contains examples of mild side effects that can occur with Neulasta and Fulphila (when taken individually):

Serious side effects

This list contains examples of serious side effects that can occur with Neulasta and Fulphila (when taken individually):

Effectiveness

The only use both Neulasta and Fulphila are approved for is reducing the risk of infection due to a condition called febrile neutropenia in people with non-myeloid cancers.

These drugs haven’t been directly compared in clinical studies, but studies have found both Neulasta and Fulphila to be effective for reducing the risk of infection due to a condition called febrile neutropenia in people with non-myeloid cancers.

Costs

According to estimates on GoodRx.com, Neulasta costs significantly more than Fulphila. The actual price you’ll pay for either drug will depend on your insurance plan, your location, and the pharmacy you use.

Generics or biosimilars

Many typical drugs that are made from chemicals have generic versions. A generic drug is an exact copy of the active ingredient in a brand-name medication. It often costs less than the brand-name version.

However, Neulasta and Fulphila are both brand-name biologic drugs, which are created from parts of living organisms. Instead of generics, biologic drugs have biosimilars. A biosimilar is a drug that’s similar to a biologic drug.

Like generics, biosimilars often cost less than the brand-name biologic they’re based on.

Neulasta has three biosimilar versions: Fulphila, Udenyca, and Ziextenzo. So Fulphila is a biosimilar of Neulasta. If you’d like to learn more about biosimilar versions of Neulasta, including Fulphila, talk with your doctor or pharmacist.

Here’s some information about what Neulasta treats and how the drug works.

Febrile neutropenia

Neulasta helps reduce the risk of infection due to a condition called febrile neutropenia in people with non-myeloid cancers.

Neutropenia is a blood condition in which neutrophil levels become low. Neutrophils are a type of white blood cell that protect your body from infection. If your neutrophil levels are low, your body won’t be able to properly fight off bacteria. So having neutropenia increases your risk for infection.

Febrile neutropenia occurs when you have neutropenia and develop a fever, which can be a sign of an infection. And having neutropenia means that you can’t fight infections as well as usual. So febrile neutropenia is a serious condition that a doctor should check out right away.

Non-myeloid cancers are cancers that don’t involve bone marrow, which is the tissue inside bones that makes blood cells. An example of a non-myeloid cancer is breast cancer.

Radiation sickness

Neulasta is also used to treat radiation sickness, a condition that occurs when you’re exposed to high levels of radiation. It may also be referred to as acute radiation syndrome.

The type of radiation sickness that Neulasta is used for is called hematopoietic subsyndrome. The amounts of radiation exposure that cause this syndrome are described as myelosuppressive, meaning they lead your bone marrow to make fewer blood cells.

How Neulasta works

Granulocyte-colony stimulating factor (G-CSF) is a hormone that causes neutrophils to grow in your bone marrow.

The active drug in Neulasta, pegfilgrastim, is a man-made copy of the G-CSF hormone your body makes naturally. Pegfilgrastim works in the same exact way that natural G-CSF does.

Neulasta aids you in creating more neutrophils and other white blood cells. This helps your body be more prepared to fight infections, prevent febrile neutropenia, and shorten how long you have neutropenia.

For hematopoietic subsyndrome due to radiation sickness, Neulasta helps your body replace white blood cells that were destroyed in the bone marrow by radiation exposure.

How long does it take to work?

Neulasta begins to work shortly after it’s injected into your body. However, clinical studies show that it may take 1 to 2 weeks for neutrophil levels to return to normal after you receive a dose of Neulasta following a round of chemotherapy.

Currently, there are no known interactions between Neulasta and alcohol.

However, alcohol may interfere with some chemotherapy drugs or make their side effects worse.

Talk with your doctor about whether alcohol is safe for you to drink during your chemotherapy treatment. (Neulasta is given after a dose of chemotherapy.)

There aren’t any known interactions between Neulasta and other medications, herbs and supplements, and foods.

Neulasta and other medications

It isn’t known whether there are any drug interactions between Neulasta and other medications. This is because no formal studies have been done to detect drug interactions. Based on how the drug works, interactions with other medications are unlikely.

If you have questions about drug interactions that may affect you, ask your doctor or pharmacist.

Neulasta and herbs and supplements

There aren’t any herbs or supplements that have been specifically reported to interact with Neulasta. However, you should still check with your doctor or pharmacist before using any of these products while taking Neulasta.

Neulasta and foods

There aren’t any foods that have been specifically reported to interact with Neulasta. If you have any questions about eating certain foods while taking Neulasta, talk with your doctor.

As with all medications, the cost of Neulasta can vary.

The actual price you’ll pay will depend on your insurance plan, your location, and the pharmacy you use.

It’s important to note that you’ll have to get Neulasta at a specialty pharmacy. This type of pharmacy is authorized to carry specialty medications. These are drugs that may be expensive or may require help from healthcare professionals to be used safely and effectively.

Your insurance plan may require you to get prior authorization before they approve coverage for Neulasta. This means that your doctor and insurance company will need to communicate about your prescription before the insurance company will cover the drug. The insurance company will review the request and let you and your doctor know if your plan will cover Neulasta.

If you’re not sure if you’ll need to get prior authorization for Neulasta, contact your insurance plan.

Financial and insurance assistance

If you need financial support to pay for Neulasta, or if you need help understanding your insurance coverage, help is available.

Amgen Inc., the manufacturer of Neulasta, offers programs called Amgen FIRST STEP and Amgen Assist 360. For more information and to find out if you’re eligible for support, call 888-657-8371 or visit the program website.

Biosimilar version

Neulasta is available in three biosimilar versions: Fulphila, Udenyca, and Ziextenzo.

A biosimilar is a drug that’s similar to a brand-name medication. A generic drug, on the other hand, is an exact copy of the active ingredient in a brand-name medication.

Biosimilars are based on biologic drugs, which are created from parts of living organisms. Generics are based on regular medications that are made from chemicals. Biosimilars and generics also tend to cost less than brand-name drugs.

To find out how the costs of Fulphila, Udenyca, and Ziextenzo compare with the cost of Neulasta, visit GoodRx.com. Again, the cost you find on GoodRx.com is what you may pay without insurance. The actual price you’ll pay will depend on your insurance plan, your location, and the pharmacy you use.

If your doctor has prescribed Neulasta and you’re interested in using Fulphila, Udenyca, and Ziextenzo instead, talk with your doctor. They may have a preference for one version or the other. You’ll also need to check your insurance plan, as it may only cover one or the other.

You should take Neulasta according to your doctor or healthcare provider’s instructions.

When to take

Neulasta comes in two forms. One is a single-dose prefilled syringe. This form is given the day after you have chemotherapy as a subcutaneous injection (an injection directly under your skin). A healthcare provider will give you the Neulasta injection, or you may be able to give yourself the injection at home after being trained.

The second form is called Neulasta Onpro. It’s an on-body injector (OBI) that a healthcare provider will apply to your stomach or the back of your arm. They’ll do this on the same day you receive chemotherapy.

Then the OBI will automatically deliver your Neulasta dose about 27 hours after being attached. This means you don’t need to return to your doctor’s office for an injection.

It’s important to note that Neulasta Onpro isn’t used to treat radiation sickness.

It isn’t known if Neulasta is safe to take during pregnancy.

Studies have been done in pregnant animals who were given filgrastim (a drug similar to Neulasta). Researchers found no increased risk of birth defects, miscarriage, or health problems for the baby or mother.

However, animal studies don’t always reflect what happens in humans. More research on Neulasta and pregnancy is needed.

If you’re pregnant or planning to become pregnant, talk with your doctor before using Neulasta. They can explain the risks and benefits of the drug as well as other treatment options.

It’s not known if Neulasta is safe to take during pregnancy. (See the “Neulasta and pregnancy” section above to learn more.) If you’re sexually active and you or your partner can become pregnant, talk with your doctor about your birth control needs while you’re using Neulasta.

It isn’t known whether it’s safe to take Neulasta while breastfeeding.

We don’t know if the active drug in Neulasta, pegfilgrastim, is present in human breast milk.

If you’re taking Neulasta and considering breastfeeding, talk with your doctor.

This drug comes with several precautions. Before taking Neulasta, talk with your doctor about your health history. Neulasta may not be right for you if you have certain medical conditions or other factors affecting your health. These include:

• Certain blood cancers. If you have a myeloid cancer (a cancer that involves bone marrow), you shouldn’t use Neulasta. The drug may cause tumor growth in people with certain blood cancers, specifically myeloid cancers. Tumors are masses of cancerous tissue. Ask your doctor what other treatments might be better choices for you.
• Sickle cell disorders. Taking Neulasta when you have a sickle cell disorder may cause a sickle cell crisis, which can be fatal. (This disorder affects hemoglobin, which is found in red blood cells.) If you have a sickle cell disorder, talk with your doctor before using Neulasta. They can recommend the best treatment options for you.
• Allergy to acrylics. If you’re allergic to acrylic adhesives, you shouldn’t use Neulasta Onpro, the Neulasta on-body injector. The device uses an acrylic adhesive. Ask your doctor if the Neulasta prefilled syringe is a good choice for you.
• Allergy to latex. If you have a latex allergy, you shouldn’t use Neulasta prefilled syringes. The needle cap on the syringes contains a natural rubber derived from latex. Ask your doctor if the Neulasta Onpro on-body injector is a good choice for you.
• Allergy to Neulasta. If you’re allergic to Neulasta or any of its ingredients, you shouldn’t use the drug. Ask your doctor about other treatment options.
• Pregnancy. It isn’t known whether Neulasta is safe to use during pregnancy. For more information, please see the “Neulasta and pregnancy” section above.
• Breastfeeding. It isn’t known whether it’s safe to take Neulasta while breastfeeding. For more information, please see the “Neulasta and breastfeeding” section above.

Note: For more information about the potential negative effects of Neulasta, see the “Neulasta side effects” section above.

Using more than the recommended dosage of Neulasta can lead to serious side effects.

Overdose symptoms

Symptoms of an overdose can include:

What to do in case of overdose

If you think you’ve taken too much of this drug, call your doctor. You can also call the American Association of Poison Control Centers at 800-222-1222 or use their online tool. But if your symptoms are severe, call 911 or go to the nearest emergency room right away.

When you get Neulasta from the pharmacy, the pharmacist will add an expiration date to the label on the box or carton. This date is typically 1 year from the date they dispensed the medication.

The expiration date helps guarantee that the medication is effective during this time. The current stance of the Food and Drug Administration (FDA) is to avoid using expired medications.

If you have unused medication that has gone past the expiration date, talk to your pharmacist about whether you might still be able to use it.

Storage

How long a medication remains good can depend on many factors, including how and where you store the medication.

You should store Neulasta prefilled syringes in a refrigerator (36°F to 46°F / 2°C to 8°C). Don’t freeze them. But if they do become frozen, let the syringes defrost in the refrigerator before you use them. If a syringe is frozen more than one time, dispose of it.

You should also dispose of any syringes that you’ve kept at room temperature for longer than 48 hours. Finally, never shake Neulasta syringes.

Disposal

Here’s some information on how to dispose of Neulasta prefilled syringes and Neulasta Onpro.

Neulasta prefilled syringes

Right after you’ve used a Neulasta prefilled syringe, dispose of it in an FDA-approved sharps disposal container. This helps prevent others, including children and pets, from taking the drug by accident or harming themselves with the needle.

You can buy a sharps container online, or ask your doctor, pharmacist, or health insurance company where to get one.

This article provides several useful tips on medication disposal. You can also ask your pharmacist for information on how to dispose of your syringes.

Neulasta Onpro

If you use Neulasta Onpro, there are special disposal instructions. After you receive your full dose, you should put Neulasta Onpro in a sharps container.

The manufacturer of Neulasta Onpro has a Sharps Disposal Container Program to help you safely dispose of Neulasta Onpro. This is offered at no additional cost to you. You can click here to sign up for the program, or call 844-696-3852.

The following information is provided for clinicians and other healthcare professionals.

Indications

Neulasta is indicated for reducing infection risk in patients with non-myeloid malignancies being treated with myelosuppressive anti-cancer treatment that causes febrile neutropenia.

Neulasta is also approved for increasing survival in people with hematopoietic subsyndrome of acute radiation syndrome (radiation sickness).

Mechanism of action

The active ingredient in Neulasta, pegfilgrastim, is a synthetic colony-stimulating factor. It binds to receptors on the cell surface of hematopoietic cells, triggering their proliferation, differentiation, and activation. This results in an increase in absolute neutrophil count (ANC).

Pharmacokinetics and metabolism

The serum half-life of Neulasta after subcutaneous administration ranges from 15 to 80 hours.

Patients with a higher body weight experienced higher systemic exposure to Neulasta in clinical trials, highlighting the importance of following weight-based dosing recommendations provided by the manufacturer.

Although the manufacturer doesn’t offer specific pharmacokinetic information with regard to duration of effect, clinical studies have shown that ANC takes approximately 10 to 14 days from the date of chemotherapy administration to recover to normal levels when Neulasta is administered the day following chemotherapy.

Neulasta peak concentration

After subcutaneous administration, peak Neulasta concentrations occur around 16 to 120 hours post-dose.

Contraindications

Neulasta is contraindicated in patients with history of serious allergic reaction to either pegfilgrastim or filgrastim.

Storage

Neulasta prefilled syringes should be refrigerated between 36°F and 46°F (2°C and 8°C). The syringes should be kept in the original carton to protect from light. Syringes left at room temperature for longer than 48 hours should be disposed of.

Do not freeze the syringes. But if the syringes become frozen, defrost them in a refrigerator before using. Dispose of any syringes that have been frozen more than one time.

Neulasta Onpro kits should be refrigerated between 36°F and 46°F (2°C and 8°C) until 30 minutes before using them. Don’t keep the kits at room temperature for more than 12 hours before using them. If the kits are kept at room temperature for longer than 12 hours, dispose of them.

Disclaimer: Medical News Today has made every effort to make certain that all information is factually correct, comprehensive, and up-to-date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or other healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.

Difference Between Filgrastim and Pegfilgrastim

The key difference between filgrastim and pegfilgrastim is that filgrastim is a medication used to treat neutropenia, which is a condition of low neutrophil count in the blood, while pegfilgrastim is a pegylated form of recombinant human colony-stimulating factor which is man-made

Filgrastim and pegfilgrastim are two types of medications. Filgrastim is a synthetic drug which is similar to the naturally produced colony-stimulating factor. It comes as an injection to treat patients having neutropenia, which is a condition of low white blood cells. Also, filgrastim stimulates the production of new white blood cells in the bone marrow, decreasing the chance of infections in patients who have cancers and undergo chemotherapy. Pegfilgrastim is an analog of filgrastim which is known as a PEGylated form of the recombinant human granulocyte colony-stimulating factor. It is also used to treat low white blood counts in the blood.

CONTENTS

1. Overview and Key Difference
2. What is Filgrastim 
3. What is Pegfilgrastim
4. Similarities Between Filgrastim and Pegfilgrastim
5. Side by Side Comparison – Filgrastim vs Pegfilgrastim in Tabular Form
6. Summary

What is Filgrastim?

Filgrastim is a medicine used to treat low neutrophil count. It is a type of biologic response modifier produced using recombinant DNA technology. It is a protein which has a molecular weight of 18‚800 daltons. Moreover, it is a type of a colony-stimulating factor and a hematopoietic agent. There are several trade names used to refer to this medication. They are Neupogen, Granix, Zarxio and Granulocyte – colony-stimulating factor. In fact, filgrastim is a support medication which stimulates the production of granulocytes in patients that have low white blood cell counts. Filgrastim not only helps to produce neutrophils, but it also helps to mature and activate neutrophils. Moreover, it stimulates the release of neutrophils from the bone marrow. Especially in patients receiving chemotherapy, filgrastim accelerates the recovery of neutrophils by reducing the neutropenic phase.

Figure 01: Filgrastim

Filgrastim can be injected or infused into a vein. Generally, this medicine should be kept inside a fridge and should be removed from it 30 minutes prior to the injection. Most importantly, it should not be shaken and kept under sunlight. The amount of filgrastim prescribed is different among individuals based on the height, weight, general health or other health problems, type of cancer or condition being treated.

What is Pegfilgrastim?

Pegfilgrastim is a PEGylated or pegylated form of recombinant human granulocyte colony-stimulating factor. It is an analog of filgrastim. The trade name of pegfilgrastim is Neulasta. Similar to filgrastim, pegfilgrastim is also a man-made drug used to treat neutropenia or the condition of low while blood cells in the blood. Pegfilgrastim stimulates the production of neutrophils in patients undergoing chemotherapy. By increasing the white blood cell production, pegfilgrastim decreases the chance of infections. Most importantly, pegfilgrastim stimulates the bone marrow to produce more white blood cells to fight against infections. Similar to filgrastim, pegfilgrastim is also injected under the skin.

What are the Similarities Between Filgrastim and Pegfilgrastim?

• Filgrastim and pegfilgrastim are two medications which are proteins.
• Pegfilgrastim is an analog of filgrastim.
• In fact, it is a longer-acting form of filgrastim.
• Both drugs are used to treat neutropenia.
• Both drugs are synthetic drugs.
• They work as biologic response modifiers.
• Both drugs mainly stimulate the production of white blood cells and decrease the chance of infections in patients who are receiving chemotherapy.
• If you have allergies, you should not take filgrastim or pegfilgrastim.
• Both filgrastim and pegfilgrastim are given as injections.

What is the Difference Between Filgrastim and Pegfilgrastim?

Filgrastim is a drug used to treat a condition called neutropenia, which causes low white blood cells in the blood due to some cancers and chemotherapy. On the other hand, pegfilgrastim is a pegylated form of recombinant human colony-stimulating factor which is man-made. So, this is the key difference between filgrastim and pegfilgrastim. Neupogen, Granix, Zarxio and Granulocyte – colony-stimulating factor are trade names of filgrastim, while Neulasta is the trade name of pegfilgrastim.

Summary – Filgrastim vs Pegfilgrastim

Filgrastim and pegfilgrastim are two drugs that are proteins. They are synthetic drugs (man-made). Both types of drugs are used to stimulate white blood cell production in patients who are undergoing chemotherapy. Both drugs stimulate the bone marrow to produce more white blood cells to fight against infections. Pegfilgrastim is a pegylated form of recombinant human colony-stimulating factor. It is a type of a longer-acting form of filgrastim. Both drugs are given as injections injected mainly under the skin. So, this summarizes the difference between filgrastim and pegfilgrastim.

Reference:

1. “Filgrastim – Drug Information – Chemocare”. Chemocare.Com, 2020, Available here.
2. “Pegfilgrastim Injection: Medlineplus Drug Information”. Medlineplus.Gov, 2020, Available here.

Image Courtesy:

1. “Filgrastim” By European Bioinformatics Institute – www.ebi.ac.uk (Public Domain) via Commons Wikimedia

PEG-FILSTIM instructions for use, price in pharmacies in Ukraine, analogues, composition, indications | PEG-FILSTIM solution for injection of the company “Biopharma”

pharmacodynamics . Pegfilgrastim is a covalent conjugate of filgrastim (recombinant human granulocyte colony-stimulating factor – G-CSF) with one molecule of polyethylene glycol (PEG) with a molecular weight of 20 kDa. Human G-CSF is a glycoprotein that regulates the production and release of neutrophils from the bone marrow.Pegfilgrastim has a prolonged effect as a result of low renal clearance.

Pegfilgrastim and filgrastim have the same mechanism of action: they significantly increase the number of neutrophils in the peripheral blood within 24 hours and slightly increase the number of monocytes and / or lymphocytes. As with filgrastim, neutrophils formed in response to pegfilgrastim therapy exhibit normal or increased functional activity (chemotaxis and phagocytosis).

Similar to other hematopoietic growth factors, G-CSF can stimulate endothelial cells in vitro . G-CSF is able to stimulate the growth of myeloid cells, including malignant cells in vitro . Similar effects are possible for some non-myeloid cells in vitro .

A single injection of PEG-Filstim after each cycle of myelosuppressive cytostatic therapy reduces the duration of neutropenia and the incidence of febrile neutropenia similar to the daily administration of filgrastim (an average of 11 daily injections).

Pharmacokinetics . After a single subcutaneous injection of pegfilgrastim, its Cmax in blood plasma is reached after 16–120 hours.

The achieved concentration of pegfilgrastim in blood plasma is maintained during the period of neutropenia after myelosuppressive chemotherapy.

The excretion of pegfilgrastim is nonlinear, dose-dependent. Excretion of pegfilgrastim from blood plasma decreases with increasing dose. The clearance of pegfilgrastim is mainly carried out by neutrophils and decreases with increasing dose of pegfilgrastim.

In accordance with the self-regulating mechanism of clearance, the concentration of pegfilgrastim in the blood plasma decreases rapidly with the beginning of the restoration of the number of neutrophils.

to reduce the duration of neutropenia and the incidence of febrile neutropenia in patients receiving chemotherapy with cytotoxic drugs for malignant diseases (with the exception of chronic myeloid leukemia and myelodysplastic syndrome).

treatment with the drug should be carried out only under the supervision of an oncologist and / or hematologist with experience in the use of G-CSF.

The vial / pre-filled syringe with the drug is intended for single use only. The drug is a sterile solution without preservatives. Before the introduction of the solution, it should be examined for the presence of foreign visible impurities. Only transparent and colorless solution is allowed. Excessive shaking can cause pegfilgrastim to aggregate, rendering it biologically inactive. Before injection, the solution in the vial / pre-filled syringe must reach room temperature.

Any unused drug or its remains should be disposed of.

PEG-Filstim is injected subcutaneously into the thigh, abdomen or shoulder in the amount of 6 mg (one vial / pre-filled syringe) at least 24 hours after each cycle of cytotoxic chemotherapy. PEG-Filstim should not be used less than 14 days before and earlier than 24 hours after cytotoxic chemotherapy.

Special groups of patients .

Renal impairment: Dose adjustment in patients with impaired renal function, including end-stage renal failure, is not recommended.

hypersensitivity to the active substance or to any auxiliary component of the drug; neutropenia in chronic myeloid leukemia and myelodysplastic syndrome.

Most adverse reactions can be caused by malignant tumors or cytotoxic chemotherapy. By the frequency of occurrence, adverse reactions registered in clinical trials are divided into: very frequent (> 10%), frequent (from> 1% to ≤ 10%) and infrequent (≤1%):

from the musculoskeletal system: very often – bone pain; often – arthralgia, myalgia, pain in the back, limbs and neck.

The body as a whole : often – chest pain (non-cardiac), pain, pain at the injection site.

From the nervous system: often – headache.

Allergic reactions: anaphylaxis, rash, urticaria, angioedema, shortness of breath, hypotension, reactions at the injection site were detected at the beginning of drug administration or during subsequent administration. If serious allergic reactions occur, appropriate treatment should be prescribed and therapy with PEG-Filstim should be discontinued.

Reactions at the injection site , including erythema at the injection site (infrequently (≥1 / 1000 to 1/100)) and pain at the injection site (often (≥1 / 100 to 1/10)), arising from primary or further treatment with pegfilgrastim.

Respiratory system disorders: rarely – interstitial pneumonia, pulmonary edema, pulmonary infiltrates and pulmonary fibrosis, some of which can lead to respiratory failure or respiratory distress syndrome, the consequences of which can be fatal.

Splenomegaly is an uncommon asymptomatic adverse event.

Very rare cases of rupture of the spleen after administration of pegfilgrastim have been reported, some with fatal outcome (see SPECIAL INSTRUCTIONS).

Acute febrile dermatosis (Sweet’s syndrome) was rarely noted (with a frequency of ≥ 0.01% to <0.1%). However, in some cases, an underlying blood disorder may be important for the development of Sweet's syndrome.

Very rare cases of skin vasculitis have been reported (0.0038%).The mechanism of vasculitis in patients receiving pegfilgrastim is unknown.

Sickle cell crisis has been reported in some patients with sickle cell disease (see SPECIAL INSTRUCTIONS).

A transient increase in the level of liver function tests is possible in patients receiving pegfilgrastim after cytotoxic chemotherapy. Liver function tests returned to baseline.

Glomerulonephritis has been reported in patients treated with pegfilgrastim.Symptoms disappeared after reduction or withdrawal of the drug. Monitoring of urine parameters is recommended.

Frequent (≥1 / 100 to 1/10)) cases of leukocytosis (100 × 10 ⁹ / L) (see SPECIAL INSTRUCTIONS) and thrombocytopenia have been reported.

Reversible mild to moderate increases in uric acid and alkaline phosphatase levels without associated clinical effects were rare; a reversible, mild to moderate increase in LDH levels without clinical effects associated with it was rare in patients receiving pegfilgrastim after cytotoxic chemotherapy.

Cases of capillary leak syndrome have been reported with the use of G-CSF in the post-marketing period. Cases of capillary leak, as a rule, occurred in patients with malignant formations, sepsis; in patients taking multiple chemotherapy drugs or undergoing apheresis (see SPECIAL INSTRUCTIONS).

Children .

The experience of using the drug in children is limited. There was a higher incidence of serious adverse reactions in children aged 0–5 years (92%) compared with that in children 6–11 years old and children ≥12 years old, respectively (80% and 67%) and adults.The most common adverse reaction was bone pain (see Pharmacodynamics and Pharmacokinetics).

Limited evidence suggests that pegfilgrastim and filgrastim are equally effective in terms of recovery time in severe neutropenia in patients with acute myeloid leukemia de novo . However, caution should be exercised when treating patients with acute myeloid leukemia de novo with pegfilgrastim, since the long-term effects of such therapy have not been established.

G-CSF can promote the growth of myeloid and some non-myeloid cells de novo .

The drug should not be used for myelodysplastic syndromes, chronic myeloid leukemia, secondary acute myeloid leukemia, since the safety and efficacy of the drug under such conditions have not been studied. The differential diagnosis of blast transformation in chronic and acute myeloid leukemia should be especially carefully carried out.

The safety and efficacy of pegfilgrastim in patients receiving high-dose chemotherapy have not been studied.

In rare cases (> 0.01% to <0.1%) after administration of G-CSF, pulmonary side effects, in particular interstitial pneumonia, have been reported. Patients with a history of pulmonary infiltrates or pneumonia are at increased risk of developing pulmonary side effects.

Cough, fever and shortness of breath in combination with radiographic infiltrative changes, deterioration of lung function and an increase in the number of neutrophils can be signs of respiratory distress syndrome (RDS) in adults.In such cases, at the discretion of the doctor, the drug should be canceled and appropriate treatment should be prescribed.

Asymptomatic cases of splenomegaly and isolated cases of rupture of the spleen after pegfilgrastim were frequently reported, some of which were fatal. The size of the spleen should be carefully monitored (using ultrasound). A diagnosis of ruptured spleen should be suspected in donors and / or patients with complaints of pain in the upper left abdomen or upper left shoulder.

Treatment with pegfilgrastim does not prevent thrombocytopenia and anemia during full dose myelosuppressive chemotherapy, so regular platelet counts and hematocrit are recommended.

The development of sickle cell crisis is associated with pegfilgrastim therapy in patients with sickle cell anemia. Physicians should carefully monitor patients with sickle cell disease when using PEG-Filstim, monitor the relevant clinical parameters and laboratory parameters, and be aware of the possible relationship between the use of PEG-Filstim, splenomegaly and vaso-occlusive crisis.

Leukocytosis 100 × 10 ⁹ / L or higher was observed in less than 1% of patients receiving pegfilgrastim.There were no reported side effects directly related to such leukocytosis. This increase in the number of leukocytes is temporary and, as a rule, is fixed 24–48 hours after the administration of pegfilgrastim and coincides with its pharmacodynamic effects. However, given the clinical effect and the possible appearance of leukocytosis during treatment, it is necessary to regularly determine the number of leukocytes. If the number of leukocytes exceeds 50 × 10 ⁹ / l, it is recommended to cancel pegfilgrastim immediately.

The safety and efficacy of pegfilgrastim in mobilizing blood stem cells in sick or healthy donors has not been adequately evaluated.

Increased hematopoietic activity of the bone marrow in response to therapy with growth factors leads to transient positive changes in bone imaging, which should be taken into account when interpreting the results.

Hypersensitivity .

In patients who received pegfilgrastim for the first time or systematically, hypersensitivity reactions, including anaphylactoid reactions, were detected.It is necessary to permanently discontinue the use of pegfilgrastim in patients with clinically significant hypersensitivity.

PEG-Filstim should not be used in patients with a history of hypersensitivity to filgrastim or pegfilgrastim. If a serious allergic reaction occurs, appropriate therapy should be started with strict monitoring of the patient’s condition for several days.

Immunogenicity .

As with all therapeutic proteins, immunogenicity is likely to develop.The development of antibodies to pegfilgrastim is usually weak. Antibody binding is expected to occur with all biological products, however, antibodies have not been associated with neutralizing activity at present.

The needle cap of the prefilled syringe may contain dry natural rubber (latex derivative), which may cause allergic reactions.

PEG-Filstim contains sorbitol. Patients with hereditary fructose intolerance should not take this drug.

PEG-Filstim contains less than 1 mmol (23 mg) of sodium in 1 dose of 6 mg, that is, the preparation practically does not contain sodium.

In order to better track the efficacy and tolerability of G-CSF, the trade name of the drug should be clearly written on the patient’s medical record.

Renal dysfunction .

Glomerulonephritis was observed in patients treated with filgrastim and pegfilgrastim. As a rule, cases of glomerulonephritis disappear after dose reduction or discontinuation of filgrastim and pegfilgrastim.Urinalysis is recommended.

The syndrome of capillary leakage was observed after administration of G-GFR and was characterized by hypotension, hypoalbuminemia, edema and blood clotting. Patients who develop symptoms of capillary leakage syndrome should be closely monitored and receive standard symptomatic treatment, including intensive care if necessary (see SIDE EFFECTS).

Disposal of an unused product and a product that has expired: It is necessary to minimize the release of the product into the environment; the drug should not be disposed of in waste water and household waste.

Application during pregnancy and lactation . There are no data on the use of pegfilgrastim in pregnant women. Reproductive toxicity has been shown in animal studies. The potential risk to humans is unknown. Pegfilgrastim should not be used in pregnant women unless clearly needed. There is no clinical experience with the drug during lactation. Therefore, it is not recommended to use pegfilgrastim during breastfeeding.

Fertility .Pegfilgrastim does not affect reproductive function or fertility in animals at a cumulative dose 6–9 times the recommended dose for humans.

The ability to influence the reaction rate when driving vehicles or other mechanisms .

Clinical studies of the effect of the drug on the ability to drive vehicles or other mechanisms have not been conducted.

PEG-Filstim should be administered 24 hours after administration of cytotoxic chemotherapeutic agents due to the sensitivity of rapidly dividing myeloid cells to cytotoxic therapy.In clinical trials, the drug was used safely 14 days before the administration of cytotoxic chemotherapeutic agents. The concomitant use of pegfilgrastim with chemotherapeutic agents in humans has not been studied. In animal studies, when pegfilgrastim was used together with 5-fluorouracil (5-FU) or other antimetabolites, an increase in myelosuppression was noted.

Possible interactions with other hematopoietic growth factors and cytokines have not been studied in clinical trials.

The possibility of interaction with lithium, which also promotes the release of neutrophils, has not been specifically investigated, so there is no confirmation that such an interaction could be harmful. The safety and efficacy of pegfilgrastim have not been studied in patients receiving chemotherapy associated with delayed myelosuppression, such as nitrosourea drugs.

Specific studies of interaction and effect on metabolism have not been carried out, however, according to clinical studies, the interaction of pegfilgrastim with other drugs has not been noted at the present time.

Incompatibility . The drug is incompatible with sodium chloride solution.

cases of overdose in humans have not been described. The maximum safe dose of pegfilgrastim that can be given as a single or multiple dose has not been determined. With the subcutaneous administration of single doses of 300 μg / kg of body weight to a small number of healthy volunteers and patients with non-small cell lung cancer, no serious side effects were noted.

In case of overdose, it is recommended to consider leukocytapheresis.

in its original packaging for protection from light at 2-8 ° C.

Do not freeze. A single accidental exposure to temperatures below 0 ° C for less than 24 hours does not adversely affect the stability of pegfilgrastim once.

The drug can be stored at room temperature (no higher than 30 ° C) once for no more than 72 hours. The drug, which has been under the influence of room temperature for more than 72 hours, should not be used.

Date added: 12.06.2021

Pegfilgrastim – instructions for use

Treatment with pegfilgrastim should be carried out only under the supervision of an oncologist or hematologist with experience in the use of G-CSF.

Limited evidence suggests that the efficacy of pegfilgrastim and filgrastim is the same in terms of the time to relieve severe neutropenia in patients with acute myeloid leukemia de novo . However, caution should be exercised when treating pegfilgrastim in patients with acute myeloid leukemia de novo , since the long-term results of such therapy have not been established.

G-CSF stimulates endothelial cells and can accelerate the growth of myeloid cells, including malignant cells, and some non-myeloid cells in vitro .

Neulastim should not be used for myelodysplastic syndromes, chronic myeloid leukemia, secondary acute myeloid leukemia, since the safety and efficacy of the drug in these groups of patients have not been evaluated. The differential diagnosis between blastotransformation in chronic myeloid leukemia and acute myeloid leukemia should be especially carefully carried out.

The safety and efficacy of pegfilgrastim in patients with acute myeloid leukemia de novo under 55 years of age with t (15; 17) translocation have not been studied.

The safety and efficacy of pegfilgrastim in patients receiving high-dose chemotherapy have not been studied.

Cough, fever and shortness of breath in combination with radiographic infiltrative changes, deterioration of lung function and an increase in the number of neutrophils can serve as signs of respiratory distress syndrome (RDS) in adults.In this case, at the discretion of the physician, pegfilgrastim should be discontinued and appropriate treatment prescribed.

There have been very rare cases of rupture of the spleen after pegfilgrastim use, some with fatal outcome. The size of the spleen should be carefully monitored. Consideration should be given to the possibility of splenomegaly or rupture of the spleen in patients with complaints of pain in the upper left abdomen and / or upper left shoulder.

Monotherapy with pegfilgrastim does not exclude the development of thrombocytopenia and anemia with continued myelosuppressive chemotherapy at full dose.It is recommended to regularly determine the number of platelets and hematocrit.

Pegfilgrastim should not be used to increase doses of cytotoxic chemotherapy above those established in the dosage regimens.

The development of sickle cell crisis was associated with pegfilgrastim therapy in patients with sickle cell anemia. Therapy with pegfilgrastim in patients with sickle cell disease should be undertaken with caution only after the potential risks and benefits have been carefully determined.

Leukocytosis 100 × 10 ⁹ / L or more is observed in less than 1% of patients receiving pegfilgrastim, is temporary and usually occurs 24–48 hours after drug administration in accordance with its pharmacodynamic effects. No side effects directly related to such leukocytosis have been described. The safety and effectiveness of pegfilgrastim in the mobilization of peripheral blood stem cells in patients have not been adequately evaluated.

Increased hematopoietic activity of the bone marrow in response to therapy with growth factors leads to transient positive changes in bone imaging, which should be taken into account when interpreting the results.

instructions for use, analogs, composition, indications

Immunostimulants, colony-stimulating factor. Code ATX : L03AA13.

Pharmacological properties

Pharmacodynamics

Human Granulocyte Colony Stimulating Factor (G-CSF) is a glycoprotein that regulates the production and release of neutrophils from the bone marrow.Pegfilgrastim is a covalent conjugate of recombinant human granulocyte colony stimulating factor G-CSF (r-metHuG-CSF) with one 20 kDa polyethylene glycol (PEG) molecule. Pegfilgrastim is a long-acting form of filgrastim due to decreased renal clearance. Pegfilgrastim and filgrastim have been shown to have the same mechanism of action, causing a significant increase in the number of neutrophils in the peripheral blood within 24 hours and a slight increase in monocytes and / or lymphocytes.Similar to filgrastim, neutrophils formed in response to pegfilgrastim show normal or increased functional activity, which is confirmed by the phagocytic chemotaxis test. Like other hematopoietic growth factors, G-CSF can stimulate human endothelial cells in vitro . G-CSF can promote the growth of myeloid cells, including malignant cells in vitro Similar effects to can be observed in vitro for some non-myelonomic cells.

In two randomized, double-blind studies in patients with high-risk stage II-IV breast cancer who received myelosuppressive chemotherapy consisting of doxorubicin and docetaxel, the use of pegfilgrastim as a single dose per cycle reduced the duration of neutropenia and the incidence of febrile neutropenia, similarly to which was observed with daily injections of filgrastim (median 11 daily injections). In the absence of the use of granulocyte colony-stimulating factor, in the case of this regimen, the average duration of grade 4 neutropenia ranged from 5 to 7 days, cases of febrile neutropenia were observed with a frequency of 30-40%.In one study (n = 157) using a fixed dose of 6 mg pegfilgrastim, the median duration of grade 4 neutropenia for the pegfilgrastim group was 1.8 days versus 1.6 days for the filgrastim group (0.23 days difference, 95% CI -0.15, 0.63). Throughout the study, the incidence of febrile neutropenia was 13% in patients treated with pegfilgrastim versus 20% in patients treated with filgrastim (difference 7%, 95% CI -19%, 5%). In the second study (n = 310), which used a weight-based dose (100 mcg / kg), the median duration of grade 4 neutropenia for the pegfilgrastim group was 1.7 days versus 1.8 days for the filgrastim group (difference 0.03 days, 95% CI -0.36, 0.30).The overall incidence of febrile neutropenia was 9% in patients receiving pegfilgrastim and 18% in patients receiving filgrastim (difference 9%, 95% CI -16.8%, -1.1%).

In a placebo-controlled, double-blind study in patients with breast cancer, the effect of pegfilgrastim on the incidence of febrile neutropenia was assessed after using a chemotherapy regimen in which the risk of developing febrile neutropenia was 10-20% (docetaxel 100 mg / m2 every 3 weeks for 4 cycles ).Nine hundred and twenty-eight patients were randomized to receive either a single dose of pegfilgrastim or placebo 24 hours (second day) after chemotherapy in each cycle. The incidence of febrile neutropenia was lower for patients receiving pegfilgrastim compared with placebo (1% versus 17%, p

A small (n = 83), randomized, double-blind, phase II trial of patients receiving chemotherapy for new-onset acute myeloid leukemia compared pegfilgrastim (6 mg single dose) with filgrastim given during induction chemotherapy.The median recovery time from severe neutropenia was estimated as 22 days in both treatment groups. Long-term results have not been studied (see PRECAUTIONS section).

In a phase II (n = 37) multicenter, randomized, open-label study of children with sarcoma treated with 100 μg / kg pegfilgrastim after the 1st cycle of therapy with vincristine, doxorubicin, and cyclophosphamide (VAdriaC / IE), a longer duration of severe neutropenia (neutrophils) was observed

Pharmacokinetics

After a single subcutaneous dose of pegfilgrastim, the peak concentration of pegfilgrastim in serum is observed in the period from 16 to 120 hours after administration, the concentration of pegfilgrastim in serum is maintained during the period of neutropenia after myelosuppressive chemotherapy.Elimination of pegfilgrastim is not linear with respect to dose; serum clearance of pegfilgrastim decreases with increasing dose. Clearance is mainly carried out by neutrophils and decreases with increasing dose of pegfilgrastim. Consistent with a self-regulating clearance mechanism, serum pegfilgrastim concentration decreases rapidly with the onset of neutrophil recovery (see Figure 1).

Figure 1. Graph of changes in the median concentration of pegfilgrastim in serum and the median of the absolute neutrophil count (ANC) in patients receiving chemotherapy after a single injection of 6 mg of pegfilgrastim

Given the neutrophil-mediated clearance mechanism, it is likely that the pharmacokinetics of pegfilgrastim are not altered in renal or hepatic impairment.In an open-label, single-dose study (n = 31), various stages of renal impairment, including end-stage renal failure, did not affect the pharmacokinetics of pegfilgrastim.

Elderly patients

The limited data available indicate that the pharmacokinetics of pegfilgrastim in elderly patients (> 65 years) are similar to those in adults.

Children’s population

The pharmacokinetics of pegfilgrastim was studied in 37 children with sarcoma who received 100 μg / kg of pegfilgrastim after completion of chemotherapy with VAdriaC / IE.The youngest age group (0-5 years) had a higher mean pegfilgrastim exposure (AUC) (± standard deviation) (47.9 ± 22.5 μgh / ml) than children aged 6-11 and 12-21 years (22.0 ± 13.1 μgh / ml and 29.3 ± 23.2 μgh / ml, respectively) (see section “Pharmacodynamics”). With the exception of the youngest age group (0-5 years), the mean AUC in children was similar to that in adult patients with high-risk stage II-IV breast cancer with 100 mcg / kg pegfilgrastim after doxorubicin / docetaxel treatment was completed (see …sections “Side effects” and “Pharmacodynamics”).

Non-clinical safety data sheet

Preclinical data from conventional multiple dose toxicity studies have revealed the expected pharmacological effects, including increased leukocyte count, myeloid hyperplasia in the bone marrow, extramedullary hematopoiesis, and enlarged spleen.

No side effects were noted in the offspring of pregnant rats treated with pegfilgrastim subcutaneously, while in rabbits, pegfilgrastim had embryo / fetal toxicity (embryo loss) at cumulative doses that were approximately 4 times the recommended human dose , toxic effects were not observed in pregnant rabbits that were exposed to the recommended human dose.In studies on rats, it has been shown that pegfilgrastim can cross the placenta. Studies in rats showed that reproductive performance, fertility, extra-cycle, days between mating and coitus, and intrauterine survival were not affected by pegfilgrastim given subcutaneously. The relevance of this data to humans is unknown.

Colony-stimulating factors in oncology | Kononenko I.B., Manzyuk L.V., Snegovoy A.V., Selchuk V.Yu.

Abstract. Febrile neutropenia during chemotherapy is a dangerous complication that leads to an increase in the absolute risk of death due to a decrease in the anti-infective response. Colony-stimulating factors (G-CSF and GM-CSF) increase the number of neutrophils and macrophages in the peripheral blood and enhance their anti-infective properties. Colony-stimulating factors are assigned according to the EORTC 2010 algorithm.

Key words: febrile neutropenia, G – CSF, GM-CSF, colony-stimulating factors.

Infections resulting from prolonged neutropenia are extremely dangerous. According to J. Klastersky, mortality from them is about 10% [1]. At John Hopkins University Hospital, an assessment was made of the absolute risk of death associated with febrile neutropenia (FN) during chemotherapy (CT). Among the 41,779 patients hospitalized for this reason, the risk of death was 9.5% (95% [CI]: 9.2%, 9.8%) [2]. CT-induced neutropenia is the most frequent dose-limiting factor in most cytostatic regimens.In clinical practice, this leads to a reduction in the planned doses of chemotherapy drugs and an increase in the interval between courses.
Previous studies have shown that underperformance of the treatment program leads to a decrease in the effectiveness of therapy and an increase in cancer mortality [3–7]. G. Bonadonna et al. demonstrated this fact in a retrospective analysis of 4 large studies that were devoted to assessing the long-term results of adjuvant chemotherapy according to the CMF scheme in patients with resectable breast cancer (BC).The median follow-up was 25.4–28.5 years. These studies retrospectively evaluated the effect of dose reduction on long-term outcomes. The overall survival rate for patients who received at least 85% of the planned dose was 40% (95% CI: 26%, 55%). In the case when the dose was <85% of the planned, the same indicator was only 21% (95% CI: 14%, 26%), and in patients with a dose of <65%, relapse-free and overall survival did not differ from that of untreated patients [eight]. Myelotoxicity remains relevant for elderly patients, in whom chemotherapy is often accompanied by an increase in the incidence of more prolonged neutropenia with severe clinical consequences and a high risk of developing FN [9–12].
In recent years, chemotherapy with a high dose load has become more often used in the treatment of solid tumors. Patients receiving this treatment are at high risk of developing FN. TAC (docetaxel / doxorubicin / cyclophosphamide) adjuvant therapy is considered the standard for patients at high risk of breast cancer recurrence [13]. As demonstrated in the GEPAR TRIO study, the administration of this regimen in neoadjuvant mode to patients with T2 – T4 breast cancer stages was accompanied by high efficiency (complete remissions – 42%, partial remissions – 46%, disease stabilization – 8%) [14] and at the same time of high toxicity [15, 16].In the BCIRG study (Breast Cancer International Research Group), chemotherapy according to the TAC scheme was performed in an adjuvant mode. Grade III – IV neutropenia in this case was observed in 66% of patients, and FN – in 25% of patients [15]. The modes of adjuvant chemotherapy of breast cancer with the inclusion of taxanes and trastuzumab also have a pronounced myelosuppressive effect in comparison with the traditional CAF and AC regimens. In the work of R.L. Bretzel et al. it was shown that chemotherapy according to the docetaxel / cyclophosphamide / trastuzumab and AC-paclitaxel / trastuzumab regimen, as well as regimens with shortened intervals between injections (AC with an interval of 14 days, AC-paclitaxel) is associated with a higher incidence of grade III-IV neutropenia and FN.The authors pointed out that this was the most common reason for lower doses of drugs and longer intervals between courses. A significant decrease in dose intensity in the study was noted in every eighth patient [17].
An important aspect of this problem is that most patients with FN require hospitalization for empiric therapy with broad-spectrum antibiotics to reduce mortality from serious infections. The results of an assessment of 60 thousand cancer patients in the United States who are hospitalized annually with FN showed that mortality from this complication in the hospital varies from 7 to 11% [18, 19].The cost of hospitalization for FN increases the overall cost of treating cancer patients. In the United States, the direct medical costs associated with hospitalization for FN have been calculated. One hospitalization for a patient with FN costs $ 10,000–20,000, and these costs do not include the salaries of medical workers and non-medical direct costs of sick leave and nurses [19–22].
The introduction into clinical practice since 1990 of recombinant forms of the natural protein granulocyte colony-stimulating factor (G-CSF) has made it possible to solve a number of important problems in this direction [23].The mechanism of G-CSF stimulation of the granulocyte link is shown in Figure 1 [24].
To date, there are publications of the results of numerous studies on the use of G-CSF in a wide range of malignant tumors and various modes of myelosuppressive chemotherapy. A meta-analysis of the first 8 randomized clinical trials using G-CSF in 1144 patients confirmed a significant reduction in the risk of developing FN (RR = 0.38, p <0.0001) and infections (RR = 0.51, p <0.001), a reduction in the recovery period the number of neutrophils (RR 0.32; 95% CI 0.23-0.46; p <0.00001) and the time of hospital stay (RR 0.63; 95% CI 0.49-0.82; p = 0 , 0006) [25, 26].The feasibility of prophylactic administration of G-CSF was demonstrated in elderly patients receiving chemotherapy, which significantly increased the chances of fulfilling the planned treatment program without reducing the doses of cytostatics [27, 28]. Side effects in the appointment of G-CSF are rare, usually bone pain, local reactions, a transient increase in the level of lactate dehydrogenase, alkaline phosphatase and uric acid [29].
In clinical practice, there are three drugs: filgrastim (non-glycosylated G-CSF), lenograstim (glycosylated G-CSF), pegfilgrastim (filgrastim combined with polyethylene glycol).
Studies have shown that, on average, 11 injections per chemotherapy cycle are sufficient to achieve normal neutrophil counts [30–33]. The need for daily administration of these drugs is due to the rather rapid excretion of G-CSF by the kidneys. Pegfilgrastim is a long-acting G-CSF that is administered once per chemotherapy cycle. The prolonged action of pegfilgrastim is due to the fact that this drug is practically not excreted in the urine, which allows it to circulate in the blood longer.Clearance (removal) of pegfilgrastim occurs when it binds to neutrophil receptors, which makes this process self-regulating: during the period of neutropenia, high concentrations of pegfilgrastim in the blood remain in the blood, providing its therapeutic effect, and as the number of neutrophils increases, its concentration rapidly decreases [34, 35].
The efficacy of all three drugs was confirmed in a large meta-analysis including a review of studies published up to 2009 [36–38]. We compared groups of patients who underwent different regimens of chemotherapy for solid tumors and lymphomas with and without primary prophylaxis of G-CSF.A number of trials have also compared different G-CSF preparations with each other. A total of 25 studies were analyzed, 5 of which evaluated the prophylactic use of pegfilgrastim [39–42]. 10 studies were carried out with filgrastim [43-51] and 5 with lenograstim [52-56]. The studied drugs demonstrated a significant reduction in the risk of developing FN. For pegfilgrastim, the relative risk was 0.30 (95% CI: 0.14-0.65), for filgrastim – 0.57 (95% CI: 0.48-0.69), for lenograstim – 0.62 (95 % CI: 0.44-0.88).A meta-analysis demonstrated significant efficacy of all three drugs (pegfilgrastim, filgrastim, and lenograstim) in relation to the risk of developing FN and the feasibility of primary prophylaxis with various chemotherapy regimens in patients with both solid tumors and lymphomas, the relative risk compared with placebo was 0.51 ( 95% CI: 0.41-0.62). A number of studies have presented data suggesting that pegfilgrastim is at least as effective and even superior to previous drugs from this group.The largest study evaluated the efficacy of pegfilgrastim administration for the primary prevention of neutropenia in a regimen with a lower risk of this complication. This randomized, double-blind, placebo-controlled study included 928 breast cancer patients who received docetaxel therapy at a dose of 100 mg / m2 every 3 weeks. This mode of chemotherapy is associated with a frequency of FN from 10 to 2% [57, 58]. Patients in one group (463 patients) received pegfilgrastim, and the comparison group (465 patients) received placebo.The use of pegfilgrastim made it possible to significantly reduce the incidence of FN – 1% compared with the placebo group – 17%. There was also a smaller number of hospitalizations – 1 and 14%, respectively, and the use of intravenous antibiotics (2% versus 10%). All differences reached statistical significance (p <0.001). Comparison of pegfilgrastim and filgrastim was carried out in 5 studies [59–63]. The authors noted that an advantage in reducing the relative risk of FN with a significant difference was associated with the use of pegfilgrastim - RR 0.66 (95% CI: 0.44–0.98) [64].Similar results were obtained in another retrospective study, which included 186 patients with various solid tumors and nonmyeloid hematological neoplasms. There was a decrease in the frequency of FN from 24% in the group of non-pegylated G-CSF to 11% in the group of pegfilgrastim [65]. It should be noted that long-acting G-CSF preparations are very convenient for outpatient use.
In clinical practice, the widespread use of G-CSF preparations for the prevention of neutropenia and infection is limited by their high cost.But in some randomized trials, the cost-effectiveness of the use of G-CSF has been demonstrated, tk. the high cost of these drugs is partially offset by a decrease in the number of hospitalizations for FN and treatment of the consequences of this complication. Back in 1993, using a cost minimization model in a key randomized study performed by J. Crawford et al. [66], it was calculated that the use of G-CSF by 20–25% reduced the total costs of treatment of patients in whom the risk of developing FN exceeded 40% [67].
To address the issue of rational use of G-CSF, including the economic aspect, an adapted strategy for the use of this group of drugs was needed. A number of leading expert committees (EORTC, ASCO, NCCN) have decided to conduct a balanced clinical assessment of the potential risk / benefit, taking into account the expected neutropenic complications and the risk of developing FN for each specific chemotherapy regimen. The basis for this approach was the results of clinical studies. In one of these trials, G-CSF was prescribed to breast cancer patients during adjuvant chemotherapy if, during the first course (AC, CAF, CMF), a decrease in the number of blood neutrophils of less than 0.5 × 109 / L was noted.For patients not included in the high-risk group (without a deep decrease in neutrophils during the first course), G-CSF was prescribed only in case of infection or delay in the administration of cytostatics due to neutropenia. This allowed a 50% increase in the proportion of patients who received treatment with an intensity of more than 85%, compared with the control data of large population studies. Hospitalization due to FN was required in 7.1% of control cases and only 2.7% in the filgrastim group (0.9% – low risk and 3.9% – high risk) [68].When making recommendations for the appointment of G-CSF, experts also took into account the characteristics of the patient (age, functional status, comorbidities), the goal of treatment, and a balanced assessment of the expected benefit of chemotherapy [69, 70].
Key Recommendations
by appointment G-KSF:
1. With the development of FN, it is mandatory to prescribe systemic antibiotic therapy with broad-spectrum drugs parenterally or enterally in patients with a low risk of severe infections.G-CSF is not a substitute for systemic antibiotics.
2. Before each course of chemotherapy, individual factors that may increase the risk of FN should be assessed (Fig. 2).
3. The use of G-CSF should be prescribed at an increased risk of FN and / or when using certain regimens of chemotherapy.
4. Assessment of risk factors is carried out immediately before the start of the chemotherapy course.
5. The use of targeted drugs (cetuximab, bevacizumab, retuximab) in combination with cytostatics increases the incidence of FN.
6. Prophylactic use of G-CSF is recommended if the risk of FN during chemotherapy is ≥20%. If the probability of FN is 10–20%, individual risk factors should be assessed.
7. If chemotherapy is palliative, the choice of a less myelosuppressive combination should be discussed or the dosage / regimen of drugs should be changed to prevent the risk of developing FN.
8. Mandatory appointment of G-CSF in intensive regimens of chemotherapy.
9. Treatment with G-CSF drugs should be carried out in the presence of FN and ineffectiveness of adequate antimicrobial therapy.This can reduce the likelihood of developing infectious complications and death from them in patients with an extremely high risk of life-threatening infections associated with FN, such as sepsis or septic shock. The general assignment algorithm is shown in Figure 2 [71].
Despite the proven feasibility of using G-CSF for various chemotherapy regimens, at present, most patients with solid tumors in Russia do not receive G-CSF. No more than 6-10% of potentially needy patients have the opportunity to receive preventive G-CSF support, which is 7-10 times lower than in Europe and the USA.It is obvious that in our country there is a high need for the most rational use of limited material resources aimed at providing drugs to cancer patients. This is largely due to economic reasons. In such a situation, it is interesting to develop a new direction, which will significantly reduce the cost of drugs and increase their availability for patients. We are talking about the development of biosimilars – biopharmaceutical drugs with a close, but not identical, parent molecule [72].
Tevagrastim is one of the first filgrastim biosimilars registered in Russia with proven efficacy and safety in accordance with the existing EMEA criteria. Pharmacodynamics, safety, pharmacokinetics and toxicological properties of Tevagrastim have been studied in an extensive preclinical program in vitro, as well as in animals. There were no significant differences in the pharmacodynamics of Tevagrastim and reference filgrastim. A phase 1 study in healthy subjects demonstrated the equivalence of single doses of Tevagrastim and original G-CSF in terms of pharmacokinetic characteristics and pharmacodynamic effects.This equivalence was evident at both doses (5 and 10 µg / kg), both after s.c. and i.v. use. Tevagrastim and original G-CSF were equally well tolerated. The results of two randomized, blind, single-dose crossover studies in 200 healthy volunteers provided compelling evidence for the bioequivalence of Tevagrastim and the original filgrastim. Clinical studies in breast cancer patients who received cytotoxic chemotherapy demonstrated Tevagrastim’s efficacy, equal to that of the original G-CSF, in terms of reducing the severity of severe neutropenia, the frequency of FN and no less safety.Tevagrastim has been shown to be safe and effective in preventing FN in 3 phase 3 studies in patients with breast cancer, lung cancer, and aggressive non-Hodgkin’s lymphoma. The safety profile of Tevagrastim in clinical trials was favorable and typical for G-CSF [72].
The efficacy and safety of another biosimilar XM-22, lipegfilgrastim, is being evaluated based on phase 2 results comparing the efficacy of different doses of lipegfilgrastim and pegfilgrastim.The duration of severe neutropenia 0.9 days in breast cancer patients after 1 course of chemotherapy was comparable in the group of patients receiving pegfilgrastim and lipegfilgrastim at a dose of 6 mg [73]. In a double-blind, randomized study, lipegfilgrastim 6 mg (n = 101) was compared with pegfilgrastim 6 mg (n = 101) in patients with locally advanced or metastatic breast cancer who received chemotherapy according to the docetaxel + doxorubicin regimen. The drugs were administered subcutaneously on the 2nd day of the chemotherapy cycle. Evaluation criteria were the duration of severe neutropenia (days with an absolute neutrophil count <0.5 × 109) during 1 cycle and cases of FN.The results of the study showed that the average duration of severe neutropenia in 1 cycle on lipegfilgrastim was 0.7 days and 0.8 days on pegfilgrastim. FN was observed during 1 cycle only in three patients receiving pegfilgrastim. Side effects characteristic of this group of drugs were observed in 28% of patients on lipegfilgrastim and in 26% of patients using pegfilgrastim. In this study, lipegfilgrastim did not differ in efficacy or side effects from pegfilgrastim [74].
Conclusion
Prophylactic administration of G-CSF, such as filgrastim, lenograstim, or pegfilgrastim, is necessary to reduce the risk of FN. Prescription of G-CSF is recommended for patients receiving chemotherapy with a high risk of FN (more than 20%), and when using chemotherapy with a risk of 10–20%, special attention should be paid to risk factors that can increase the likelihood of developing FN. Clinical data show that filgrastim, lenograstim, and pegfilgrastim have clinical efficacy and are recommended for use.

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First biosimilar products of filgrastim | Weekly PHARMACY

On 22 February, the European Medicines Agency (EMEA) approved biosimilar preparations of granulocyte colony-stimulating factor (G-CSF) from Teva, ratiopharm and CT Arzneimittel indicated for use in neutropenia caused by chemotherapy.While companies will have to work hard to market these products, if approved by the European Commission, they will pose a serious threat to Amgen as they compete with its Neupogen (filgrastim) and Neulasta (pegfilgrastim) in leading European markets. Filgrastim increases the number of neutrophilic granulocytes in the peripheral blood and reduces the incidence of infectious complications in neutropenia.

Biosimilar products of filgrastim (G-CSF) will be marketed by ratiopharm, Teva and CT Arzneimittel under the trade names Ratiograstim / ratiopharm filgrastim, TevaGrastim and Biograstim, respectively.The companies expect to receive approval from the European Commission within the next few months.

For Teva, this is the first biosimilar product approved in developed country markets. Until now, the company has marketed biogenerics only in Eastern Europe, Mexico and some other countries.

The high cost of the original filgrastim drug is a major obstacle to its widespread use in many European countries. The possibility of purchasing a cheaper analogue will allow more patients to receive the necessary treatment.

The approval of biosimilars filgrastim will be a new challenge for Amgen following the approval of those of erythropoietin-alpha in June 2007 (see APTEKA Weekly No. 27 (598) of 09.07.2007). Thus, Neupogen and Neulasta accounted for more than 30% of the company’s income in 2006, and in 12 months to October 2007, Neupogen’s sales in the EU amounted to 300 million dollars. USA.

Adapted from
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www1.ratiopharm.comrel = “nofollow”>

Article-03

Daptomycin as an antibiotic from the group of cyclic lipopeptides has been known to the world since 1985, when it was first obtained from the soil microorganism Streptomyces roseosporus by employees of Eli Lilly and Company.However, it took 18 difficult and not always successful years from its inception before Cubist Pharmaceuticals Inc. patented a medicine based on this antibiotic in 2003. This is how the history of the fight against infections caused by gram-positive bacteria, which pose a particular threat to public health, began.

Despite its effectiveness in combating pathogenic microflora, which is resistant to other known drugs, daptomycin-containing preparations in liquid form are very unstable.Even in the form of a lyophilisate for the preparation of solutions, this drug has very harsh storage conditions – from 2 ⁰ C to 8 ⁰ C.

Until September 2020, the only company capable of supplying a drug based on daptomycin to Russia was Pateon Italy S.p.A. On the one hand, it may seem that foreign products are manufactured strictly in accordance with the requirements of the Good Manufacturing Practice, however, on the other, less obvious side, in conditions when both production and quality control, and even packaging are completely imported, pricing is not so favorable. for suffering patients.In terms of imports, the price of products is highly dependent on the situation on the world market and on political games, which often neglect the health and well-being of us, ordinary people. World leaders are constantly frightened not only by new sanctions, but also by the cessation of supplies and trade.

The current year has revealed another latent threat of imported goods – dependence on the epidemiological situation in the manufacturing country and in the world as a whole. The closure of factories for quarantine and the transition to remote work are not the measures that a pharmaceutical company can afford, however, intermediaries – importers, distributors – are subject to general requirements that they are forced to obey regardless of their desire.