Fulphila

Pegfilgrastim-jmdb is a covalent conjugate of recombinant methionyl human G-CSF and monomethoxypolyethylene glycol. Recombinant methionyl human G-CSF is a water-soluble 175 amino acid protein with a molecular weight of approximately 19 kilodaltons (kD). Recombinant methionyl human G-CSF is obtained from the bacterial fermentation of a strain of E coli transformed with a genetically engineered plasmid containing the human G-CSF gene. To produce pegfilgrastim-jmdb a 20 kD monomethoxypolyethylene glycol molecule is covalently bound to the N-terminal methionyl residue of recombinant methionyl human G-CSF. The average molecular weight of pegfilgrastim-jmdb is approximately 39 kD.

Fulphila (pegfilgrastim-jmdb) injection is intended for subcutaneous use only and is supplied in a single-dose prefilled syringe with a 29 gauge needle, with UltraSafe Passive Plus ™ Needle Guard. The prefilled syringe does not bear graduation marks and is designed to deliver the entire contents of the syringe (6 mg/0.6 mL).

The delivered 0.6 mL dose from the prefilled syringe contains 6 mg pegfilgrastim-jmdb (based on protein mass only) in a sterile, clear, colorless, preservative-free solution (pH 4.0) containing acetate (0.7 mg), D-sorbitol (30 mg), polysorbate 20 (0.024 mg) and sodium (0.01 mg) in Water for Injection, USP.

The following serious adverse reactions are discussed in greater detail in other sections of the labeling:

• Splenic Rupture [See WARNINGS AND PRECAUTIONS]
• Acute Respiratory Distress Syndrome [See WARNINGS AND PRECAUTIONS]
• Serious Allergic Reactions [See WARNINGS AND PRECAUTIONS]
• Use in Patients with Sickle Cell Disorders [See WARNINGS AND PRECAUTIONS]
• Glomerulonephritis [See WARNINGS AND PRECAUTIONS]
• Leukocytosis [See WARNINGS AND PRECAUTIONS]
• Capillary Leak Syndrome [See WARNINGS AND PRECAUTIONS]
• Potential for Tumor Growth Stimulatory Effects on Malignant Cells [See WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Pegfilgrastim clinical trials safety data are based upon 932 patients receiving pegfilgrastim in seven randomized clinical trials. The population was 21 to 88 years of age and 92% female. The ethnicity was 75% Caucasian, 18% Hispanic, 5% Black, and 1% Asian. Patients with breast (n = 823), lung and thoracic tumors (n = 53) and lymphoma (n = 56) received pegfilgrastim after nonmyeloablative cytotoxic chemotherapy. Most patients received a single 100 mcg/kg (n = 259) or a single 6 mg (n = 546) dose per chemotherapy cycle over 4 cycles.

The following adverse reaction data in Table 2 are from a randomized, double-blind, placebo-controlled study in patients with metastatic or non-metastatic breast cancer receiving docetaxel 100 mg/m² every 21 days (Study 3). A total of 928 patients were randomized to receive either 6 mg pegfilgrastim (n = 467) or placebo (n = 461). The patients were 21 to 88 years of age and 99% female. The ethnicity was 66% Caucasian, 31% Hispanic, 2% Black, and < 1% Asian, Native American, or other.

The most common adverse reactions occurring in ≥ 5% of patients and with a between-group difference of ≥ 5% higher in the pegfilgrastim arm in placebo-controlled clinical trials are bone pain and pain in extremity.

Table 2: Adverse Reactions with ≥ 5% Higher Incidence in Pegfilgrastim Patients Compared to Placebo in Study 3

In clinical studies, leukocytosis (WBC counts > 100 x 109/L) was observed in less than 1% of 932 patients with non-myeloid malignancies receiving pegfilgrastim. No complications attributable to leukocytosis were reported in clinical studies.

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to pegfilgrastim in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.

Binding antibodies to pegfilgrastim were detected using a BIAcore assay. The approximate limit of detection for this assay is 500 ng/mL. Pre-existing binding antibodies were detected in approximately 6% (51/849) of patients with metastatic breast cancer. Four of 521 pegfilgrastimtreated subjects who were negative at baseline developed binding antibodies to pegfilgrastim following treatment. None of these 4 patients had evidence of neutralizing antibodies detected using a cell-based bioassay.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of pegfilgrastim products. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• Splenic rupture and splenomegaly (enlarged spleen) [see WARNINGS AND PRECAUTIONS]
• Acute respiratory distress syndrome (ARDS) [see WARNINGS AND PRECAUTIONS]
• Allergic reactions/hypersensitivity, including anaphylaxis, skin rash, and urticaria, generalized erythema, and flushing [see WARNINGS AND PRECAUTIONS]
• Sickle cell crisis [see WARNINGS AND PRECAUTIONS]
• Glomerulonephritis [see WARNINGS AND PRECAUTIONS]
• Leukocytosis [see WARNINGS AND PRECAUTIONS]
• Capillary Leak Syndrome [see WARNINGS AND PRECAUTIONS]
• Injection site reactions
• Sweet's syndrome, (acute febrile neutrophilic dermatosis), cutaneous vasculitis

Fulphila™
(FULL-fil-ah)
(pegfilgrastim-jmdb) Injection Single-Dose Prefilled Syringe

What is Fulphila?

Fulphila 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.

Do not take Fulphila if you have had a serious allergic reaction to pegfilgrastim or filgrastim products.

Before you receive Fulphila, 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 Fulphila will harm your unborn baby.
• are breastfeeding or plan to breastfeed. It is not known if pegfilgrastim 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.

How will I receive Fulphila?

• Fulphila is given as an injection under your skin (subcutaneous injection) by a healthcare provider. If your healthcare provider decides that the subcutaneous injections can be given at home by you or your caregiver, follow the detailed “Instructions for Use” that comes with your Fulphila for information on how to prepare and inject a dose of Fulphila.
• You and your caregiver will be shown how to prepare and inject Fulphila before you use it.
• You should not inject a dose of Fulphila to children weighing less than 45 kg from a Fulphila prefilled syringe. A dose less than 0.6 mL (6 mg) cannot be accurately measured using the Fulphila prefilled syringe.
• If you are receiving Fulphila because you are also receiving chemotherapy, the last dose of Fulphila should be injected at least 14 days before and 24 hours after your dose of chemotherapy.
• If you miss a dose of Fulphila, talk to your healthcare provider about when you should give your next dose.

What are possible side effects of Fulphila?

Fulphila may cause serious side effects, including:

• Spleen rupture. Your spleen may become enlarged and can rupture. A ruptured spleen can cause death. Call your healthcare provider right away if you have pain in the left upper stomach area or your left shoulder.
• A serious lung problem called Acute Respiratory Distress Syndrome (ARDS). Call your healthcare provider or get emergency care right away if you have shortness of breath with or without a fever, trouble breathing, or a fast rate of breathing.
• Serious allergic reactions. Fulphila 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 any of these symptoms, stop using Fulphila and call your healthcare provider or get emergency medical help right away.
• Sickle cell crises. You may have a serious sickle cell crisis if you have a sickle cell disorder and receive Fulphila. Serious sickle cell crises have happened in people with sickle cell disorders receiving Fulphila that has sometimes led to death. Call your healthcare provider right away if you have symptoms of sickle cell crisis such as pain or difficulty breathing.
• Kidney injury (glomerulonephritis). Fulphila 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
  • you urinate less than usual
• Increased white blood cell count (leukocytosis). Your healthcare provider will check your blood during treatment with Fulphila.
• Capillary Leak Syndrome. Fulphila 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

The most common side effects of Fulphila are pain in the bones, arms, and legs.

These are not all the possible side effects of Fulphila.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Fulphila?

• Store Fulphila in the refrigerator between 36°F to 46°F (2°C to 8°C).
• Do not freeze. If Fulphila is accidently frozen, allow the prefilled syringe to thaw in the refrigerator before injecting.
• Do not use a Fulphila prefilled syringe that has been frozen more than 1 time. Use a new Fulphila prefilled syringe.
• Throw away (dispose of) any Fulphila that has been left at room temperature, 68°F to 77°F (20°C to 25°C) for more than 72 hours or frozen more than 1 time.
• Keep the prefilled syringe in the original carton to protect from light.
• Do not shake the prefilled syringe.
• Take Fulphila out of the refrigerator 30 minutes before use and allow it to reach room temperature before preparing an injection.

Keep the Fulphila prefilled syringe out of the reach of children.

General information about the safe and effective use of Fulphila.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Fulphila for a condition for which it was not prescribed. Do not give Fulphila to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about Fulphila that is written for health professionals.

What are the ingredients in Fulphila?

Active ingredient: pegfilgrastim-jmdb

Inactive ingredients: acetate, D-sorbitol, polysorbate 20, and sodium in Water for Injection.

This Patient Information has been approved by the U.S. Food and Drug Administration.

Instructions for Use

FULPHILA™
(FULL-fil-ah)
(pegfilgrastim-jmdb) injection, for subcutaneous use

Single-Dose Prefilled Syringe

Guide to Parts

Important Information

Read the Patient Information for important information you need to know about Fulphila before using these Instructions for Use.

Storing the Fulphila prefilled syringe

• Store Fulphila in the refrigerator between 36°F to 46°F (2°C to 8°C).
• Do not freeze. If Fulphila is accidentally frozen, allow the prefilled syringe to thaw in the refrigerator before injecting.
• Do not use a Fulphila prefilled syringe that has been frozen more than 1 time. Use a new Fulphila prefilled syringe.
• Throw away (dispose of) any Fulphila that has been left at room temperature, 68°F to 77°F (20°C to 25°C) for more than 72 hours or frozen more than 1 time. See Step 4: Disposing of used prefilled syringes.
• Keep the prefilled syringe in the original carton to protect from light.
• For questions about storage, contact your healthcare provider or pharmacist.
• Keep the Fulphila prefilled syringe out of the reach of children.

Before you use a Fulphila prefilled syringe, read this important information:

• It is important that you do not try to give yourself the injection unless you have received training from your healthcare provider.
• The prefilled syringe has a needle safety guard that will be activated to cover the needle after the injection is given. The needle guard will help prevent needlestick injuries to anyone who handles the prefilled syringe after the injection has been given.
• Make sure that the name Fulphila appears on the carton and prefilled syringe label.
• Fulphila is given as an injection into the tissue just under the skin (subcutaneous injection).
• You should not inject a dose of Fulphila to children weighing less than 45 kg from a Fulphila prefilled syringe. A dose less than 0.6 mL (6 mg) cannot be accurately measured using the Fulphila prefilled syringe.
• Do not use a prefilled syringe after the expiration date on the label.
• Do not shake the prefilled syringe.
• Do not use the prefilled syringe if the carton is open or damaged.
• Do not remove the gray needle cap from the prefilled syringe until you are ready to inject.
• Do not use the prefilled syringe if it has been dropped on a hard surface. The syringe may be broken even if you cannot see the break. Use a new prefilled syringe.
• Do not attempt to activate the prefilled syringe prior to injection.
• Do not attempt to remove the needle safety guard from the prefilled syringe.
• Do not attempt to remove the label from the prefilled syringe barrel before injecting your dose of Fulphila.

Call your healthcare provider if you have any questions.

Step 1: Gather supplies

A -Find a clean, well-lit and flat work surface, such as a table.

B -Take the prefilled syringe carton out of the refrigerator and place it on your clean work surface. Allow it to reach room temperature for 30 minutes before giving an injection.

C Remove the prefilled syringe tray from the carton.

D - Wash your hands thoroughly with soap and water.

E - Gather the supplies for the injection:

• 1 alcohol wipe
• 1 cotton ball or gauze pad
• 1 adhesive bandage
• an FDA-cleared sharps disposal container

Step 2: Prepare for injection

F - Open the tray by peeling away the cover. Grab the needle safety guard to remove the prefilled syringe from the tray.

For safety reasons:

• Do not grab the plunger rod.
• Do not grasp the gray needle cap.

G - Inspect the medicine and prefilled syringe.

Make sure the medicine in the prefilled syringe is clear and colorless.

Do not use the prefilled syringe if:

• The medicine is cloudy or discolored, or contains flakes or particles.
• The prefilled syringe has been dropped.
• Any part appears cracked or broken.
• The gray needle cap is missing or not securely attached.
• The expiration date printed on the label has passed.

In all cases, use a new prefilled syringe and call your healthcare provider.

H - Prepare and clean the injection site.

There are 4 injection sites that you can use:

• thigh
• stomach area (abdomen), except for a 2-inch area right around the navel (belly button)
• upper outer area of the buttocks (only if someone else is giving you the injection), and
• the outer area of the upper arm (only if someone else is giving you the injection).

Clean the injection site with an alcohol wipe. Let the skin dry.

• Do not touch this area again before injecting.
• Do not inject into areas where the skin is tender, bruised, red, or hard. Avoid injecting into areas with scars or stretch marks.
• If you want to use the same injection site, make sure it is not the same spot on the injection site you used for a previous injection.

I - Hold the prefilled syringe by the needle safety guard. When ready, carefully pull the gray needle cap straight off and away from the body.

• Do not twist or bend the gray needle cap.
• Do not hold the prefilled syringe by the plunger rod.
• Do not put the gray needle cap back onto the prefilled syringe. Dispose of (throw away) the gray needle cap in your household trash.

Step 3: Inject the dose

J - Pinch the cleaned injection site to create a firm surface.

!  Keep skin pinched while injecting.

K - Hold the pinch. Insert the needle into the skin between 45 to 90 degrees.

• Do not touch the cleaned area of the skin

L - Using slow and constant pressure, push the plunger rod until it reaches the bottom.

! The plunger must be pushed fully in order to inject the full dose.

M - Once the entire dose has been injected, the needle safety guard will be triggered. You can do either of the following:

• Release the plunger until the entire needle is covered and then remove the needle from the injection site.
  or
• Gently remove the needle from the injection site and release the plunger until the entire needle is covered by the needle safety guard.

After releasing the plunger, the needle safety guard will safely cover the injection needle.

• Once the needle has been removed from the injection site, dispose of the syringe and needle in your sharps disposal container right away. See “Step 4: Disposing of used prefilled syringes”.
  • If the needle safety guard is not activated or only partially activated, discard the product (without replacing the needle cap). See “Step 4: Disposing of used prefilled syringes”.
  • If your injection is given by another person, they should also be careful when removing the needle from your skin in order to prevent accidental needlestick injury and possible infections.
  • When you remove the syringe, if it looks like the medicine is still in the syringe barrel, this means you have not received the full dose. Call your healthcare provider right away.

N -Examine the injection site. If there is blood, press a cotton ball or gauze pad on the injection site. Do not rub the injection site. Apply an adhesive bandage if needed.

Step 4: Disposing of used prefilled syringes

• Put the used prefilled syringe in an FDA-cleared sharps disposal container right away after use. Do not throw away the syringe in the household trash.
• If you do not have an FDA-cleared sharps disposal container, you may use a household container that is:
  • made of heavy-duty plastic
  • can be closed with a tight-fitting, puncture-resistant lid without sharps being able to come out
  • upright and stable during use
  • leak-resistant
  • properly labeled to warn of hazardous waste inside the container
• When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at http://www.fda.gov/safesharpsdisposal.

Important: Keep the sharps disposal container out of the reach of children.

• Do not reuse the prefilled syringe.
• Do not recycle prefilled syringes or throw them into household waste.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

The following serious adverse reactions are discussed in greater detail in other sections of the labeling:

• Splenic Rupture [See WARNINGS AND PRECAUTIONS]
• Acute Respiratory Distress Syndrome [See WARNINGS AND PRECAUTIONS]
• Serious Allergic Reactions [See WARNINGS AND PRECAUTIONS]
• Use in Patients with Sickle Cell Disorders [See WARNINGS AND PRECAUTIONS]
• Glomerulonephritis [See WARNINGS AND PRECAUTIONS]
• Leukocytosis [See WARNINGS AND PRECAUTIONS]
• Capillary Leak Syndrome [See WARNINGS AND PRECAUTIONS]
• Potential for Tumor Growth Stimulatory Effects on Malignant Cells [See WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Pegfilgrastim clinical trials safety data are based upon 932 patients receiving pegfilgrastim in seven randomized clinical trials. The population was 21 to 88 years of age and 92% female. The ethnicity was 75% Caucasian, 18% Hispanic, 5% Black, and 1% Asian. Patients with breast (n = 823), lung and thoracic tumors (n = 53) and lymphoma (n = 56) received pegfilgrastim after nonmyeloablative cytotoxic chemotherapy. Most patients received a single 100 mcg/kg (n = 259) or a single 6 mg (n = 546) dose per chemotherapy cycle over 4 cycles.

The following adverse reaction data in Table 2 are from a randomized, double-blind, placebo-controlled study in patients with metastatic or non-metastatic breast cancer receiving docetaxel 100 mg/m² every 21 days (Study 3). A total of 928 patients were randomized to receive either 6 mg pegfilgrastim (n = 467) or placebo (n = 461). The patients were 21 to 88 years of age and 99% female. The ethnicity was 66% Caucasian, 31% Hispanic, 2% Black, and < 1% Asian, Native American, or other.

The most common adverse reactions occurring in ≥ 5% of patients and with a between-group difference of ≥ 5% higher in the pegfilgrastim arm in placebo-controlled clinical trials are bone pain and pain in extremity.

Table 2: Adverse Reactions with ≥ 5% Higher Incidence in Pegfilgrastim Patients Compared to Placebo in Study 3

In clinical studies, leukocytosis (WBC counts > 100 x 109/L) was observed in less than 1% of 932 patients with non-myeloid malignancies receiving pegfilgrastim. No complications attributable to leukocytosis were reported in clinical studies.

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to pegfilgrastim in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.

Binding antibodies to pegfilgrastim were detected using a BIAcore assay. The approximate limit of detection for this assay is 500 ng/mL. Pre-existing binding antibodies were detected in approximately 6% (51/849) of patients with metastatic breast cancer. Four of 521 pegfilgrastimtreated subjects who were negative at baseline developed binding antibodies to pegfilgrastim following treatment. None of these 4 patients had evidence of neutralizing antibodies detected using a cell-based bioassay.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of pegfilgrastim products. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• Splenic rupture and splenomegaly (enlarged spleen) [see WARNINGS AND PRECAUTIONS]
• Acute respiratory distress syndrome (ARDS) [see WARNINGS AND PRECAUTIONS]
• Allergic reactions/hypersensitivity, including anaphylaxis, skin rash, and urticaria, generalized erythema, and flushing [see WARNINGS AND PRECAUTIONS]
• Sickle cell crisis [see WARNINGS AND PRECAUTIONS]
• Glomerulonephritis [see WARNINGS AND PRECAUTIONS]
• Leukocytosis [see WARNINGS AND PRECAUTIONS]
• Capillary Leak Syndrome [see WARNINGS AND PRECAUTIONS]
• Injection site reactions
• Sweet's syndrome, (acute febrile neutrophilic dermatosis), cutaneous vasculitis

Read the entire FDA prescribing information for Fulphila (Pegfilgrastim-jmdb Injection, for Subcutaneous Use)

You should not use Fulphila if you are allergic to Fulphila or filgrastim (Neupogen).

Tell your doctor if you have ever had:

• sickle cell disorder;

• kidney disease;

• chronic myeloid leukemia;

• radiation treatment;

• myelodysplasia (also called "preleukemia"); or

• a latex allergy.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant. If you are pregnant, your name may be listed on a pregnancy registry to track the effects of pegfilgrastim on the baby.

It may not be safe to breast-feed while using this medicine. Ask your doctor about any risk.

Fulphila is injected under the skin, usually once per chemotherapy cycle. A healthcare provider may teach you how to properly use the medication by yourself.

Fulphila should not be given within 14 days before or 24 hours after you receive chemotherapy.

Read and carefully follow any Instructions for Use provided with your medicine. Do not use Fulphila if you don't understand all instructions for proper use. Ask your doctor or pharmacist if you have questions.

Prepare your injection only when you are ready to give it. Do not use if the medicine looks cloudy, has changed colors, or has particles in it. Call your pharmacist for new medicine.

Do not shake the prefilled syringe or you may ruin the medicine.

The Neulasta Onpro Injector is a special device placed on the skin that delivers your Fulphila dose at a specific time. You will need to wear the device for 27 hours before the dose begins. The timed dose will then be released from the device slowly over a 45-minute period.

While wearing Neulasta Onpro, you or a caregiver will need to check the device to make sure it is working properly.

Each prefilled syringe or Onpro Injector is for one use only. Throw it away after one use, even if there is still medicine left inside.

You may need frequent medical tests to help your doctor determine how long to treat you with Fulphila.

Store Fulphila in its original package in the refrigerator, protected from light. Do not freeze.

Take a prefilled syringe out of the refrigerator and let it reach room temperature for 30 minutes before injecting your dose.

Throw away any unused Fulphila syringe that has been left at room temperature for longer than 72 hours, or any Neulasta syringe that has been left at room temperature for longer than 48 hours.

Keep Neulasta Onpro refrigerated until you are ready to wear it. Do not use an Onpro device that has been left out of a refrigerator for longer than 12 hours.

Use a needle and syringe only once and then place them in a puncture-proof "sharps" container. Follow state or local laws about how to dispose of this container. Keep it out of the reach of children and pets.