Nerlynx (Neratinib) - Oral

What Is Nerlynx?

Nerlynx (neratinib) is a kinase—a type of protein—inhibitor used in people with human epidermal growth factor receptor 2 positive (HER2+) breast cancer. This orally administered prescription medication works by binding to epidermal growth factor (EGFR), which is a type of protein. Nerlynx is Food and Drug Administration (FDA) approved for adults 18 and older and is often supplemented with loperamide or Xeloda (capecitabine).

The EGFR family includes HER2. High amounts of EGFR can help cancer cells quickly divide.

High amounts of HER2 are linked to abnormal changes in breast cells that may lead to aggressive cancer. As such, Nerlynx works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of dangerous cancer cells.

Nerlynx is available for consumption in oral tablet form.

What Is Nerlynx Used For?

Breast cancer is very common in people assigned female at birth. In 2021, breast cancer affected about 300,000 people assigned female at birth in the United States (U.S.). Additionally, in 2021, breast cancer was estimated to have caused more than 43,000 deaths in the U.S.

Breast cancer has many types. In conjunction, HER2+ breast cancer is positive for HER2 receptors (binding sites) on some breast cancer cells. HER2+ breast cancer makes up about 15% of all breast cancer types.

In general, Nerlynx can be used for people with HER2+ breast cancer with the following details:

• By itself: Individuals with HER2+ early breast cancer (EBC) will usually go through surgery first before receiving Herceptin (trastuzumab) chemotherapy combined with one of the following three options: Abraxane (paclitaxel), Taxotere (docetaxel), or Taxotere plus Paraplatin (carboplatin). After trastuzumab-based therapy, Nerlynx will then be taken by itself for up to one year.
• In combination with Xeloda: Nerlynx can be used with Xeloda in people with HER2+ breast cancer that has advanced or metastasized (spread) after being treated by two or more anti-HER2-based therapies.

Since we mentioned some other treatments, in addition to Nerlynx for HER2+ breast cancer, refer below for important details about them:

• Herceptin has many biosimilars. Therefore, since trastuzumab is a biologic made from living things, it isn’t referred to as a brand or generic—like chemical-based medications. Instead of brand-name, Herceptin is known as the reference product. Instead of generics, Herzuma, Kanjinti, Ogivri, Ontruzant, and Trazimera are biosimilars. Trastuzumab prevents cancer cells from growing by blocking HER2 binding sites.
• Abraxane is a microtubule inhibitor. Microtubules are made from proteins and are found inside cells. By inhibiting microtubules, Abraxane prevents cancer cells from dividing.
• Taxotere is also a microtubule inhibitor.
• Paraplatin is considered an alkylating agent, which damages the DNA in cancer cells to prevent them from multiplying.
• Xeloda is inactive until taken by mouth. Once it’s in the human body, Xeloda turns into its active version—fluorouracil. Xeloda and fluorouracil prevent cancer cells from growing by blocking the cells’ ability to process RNA and make more DNA and proteins.
  

How to Take Nerlynx

To prevent severe diarrhea, loperamide 2-milligram pills are recommended with Nerlynx therapy with the following details:

• First 14 days of Nerlynx treatment: Take two pills of loperamide by mouth three times daily. 
• On days 15 through 56 of Nerlynx therapy: Take two pills of loperamide by mouth twice daily.
• After day 56 of Nerlynx treatment: Take two pills of loperamide as needed. Take enough loperamide to achieve one to two bowel movements every day, but don’t take more than 16 milligrams per day—which is eight pills of loperamide 2-milligram in a 24-hour period.  

As for how to take Nerlynx, refer to the following details:

• If Nerlynx is used by itself: The usual Nerlynx dosage is 240 milligrams—six tablets of 40 milligrams—by mouth every day with food for one year unless the breast cancer comes back sooner.
• If Nerlynx is combined with Xeloda: The typical Nerlynx dose is 240 milligrams by mouth every day with food unless the breast cancer further spreads or side effects are intolerable. 

In general, try to take Nerlynx at the same time every day. Swallow the whole tablet. Don’t chew, crush, or split the tablet.

Storage

Nerlynx isn’t usually available at your local retail pharmacy. You and your healthcare provider may need to coordinate with a specialty pharmacy to get this medication.

After receiving this medication from the specialty pharmacy, store Nerlynx at room temperature—which is 68 to 77 degrees F with a safe short-term range of 59 to 86 degrees F. Do not store in a bathroom.

As for traveling, be familiar with the regulations of your final destination. In general, keep Nerlynx in its original container or packaging—with your name on it—from the pharmacy. Also, consider having a copy of your Nerlynx prescription.

What Are the Side Effects of Nerlynx?

This is not a complete list of side effects, and others may occur. A healthcare provider can advise you on side effects. If you experience other effects, contact your healthcare provider. You may report side effects to the FDA at fda.gov/medwatch or 1-800-FDA-1088.

Common Side Effects

After surgery and trastuzumab-based therapy, people with HER2+ EBC experience the following common side effects with Nerlynx treatment by itself:

• Abnormal liver function tests (LFTs)
• Appetite changes
• Bloating
• Diarrhea
• Dry mouth
• Dry skin
• Indigestion
• Muscle spasms
• Nail changes
• Nausea and vomiting
• Nose bleeds
• Rash
• Stomach pain
• Tiredness
• Urinary tract infections (UTIs)
• Weight loss

Common side effects for a combination of Nerlynx and Xeloda treatment may include:

• Appetite changes
• Back pain
• Bloating
• Constipation
• Diarrhea
• Dizziness
• Joint stiffness or pain
• Kidney impairment
• Limited energy and strength
• Muscle spasms
• Nausea and vomiting
• Tiredness
• Upper respiratory tract infections (URTIs)
• Urinary tract infections (UTIs)
• Weight loss

Severe Side Effects

This is not a complete list of side effects, and others may occur. A healthcare provider can advise you on side effects. If you experience other effects, contact your healthcare provider. You may report side effects to the FDA at fda.gov/medwatch or 1-800-FDA-1088.

Although diarrhea is a common side effect, it can be severe in some cases—even with loperamide treatment. If loperamide isn’t lessening your number of loose stools, drink more fluids. Also, immediately notify your healthcare provider to discuss any next steps.

Slightly abnormal LFTs are also common with Nerlynx.

However, contact your healthcare provider and seek medical attention if you notice the following symptoms of liver damage:

• Dark urine
• Nausea and vomiting
• Jaundice (yellowing of eyes and skin)
• Stomach pain

Long-Term Side Effects

Nerlynx isn’t linked with a higher risk of developing other cancers. Nerlynx is also not connected with toxicity to the blood cells, heart, and lungs.

Dosage: How Much Nerlynx Should I Take?

Modifications

Users should be aware of the following before beginning Nerlynx:

• People experiencing diarrhea and other side effects: If you are concerned about your diarrhea or other side effects, immediately talk with your healthcare provider, who will adjust the Nerlynx dose to lessen the severity of your side effects.
• People with liver concerns: If you have severe liver impairment, your healthcare provider may start you at a lower Nerlynx dose of 80 milligrams—two of the 40-milligram tablets—daily. Your healthcare provider will continue to closely monitor your LFTs to adjust the dose or completely stop Nerlynx accordingly.
• Pregnant or nursing parents: Nerlynx may have serious negative effects on unborn or nursing babies. Therefore, while taking Nerlynx, use an effective form of birth control. Potential users should consult a healthcare provider about starting Nerlynx if they plan on becoming or are currently pregnant. As for breastfeeding, the manufacturer—Puma Biotechnology—doesn’t recommend it.
• Children: The safety and efficacy of Nerlynx in pediatric patients have not been established. Nerlynx is only recommended for people 18 and older.
• Older adults: Per the results of the ExteNET trial and the NALA trial, no meaningful differences in effectiveness were observed between people older than 65 and those younger than 65. However, the serious negative reactions most frequently reported in the older than 65 cohort per the ExteNET trial were vomiting (2.3%), diarrhea (1.7%), renal failure (1.7%), and dehydration (1.2%). Additionally, per the NALA trial, serious negative reactions most frequently reported in the 65 and older cohort were diarrhea (16%), acute kidney injury (8%), and dehydration (7%).
• Hepatic impairment: No dose modifications are recommended for patients with mild to moderate hepatic impairment.
  

Missed Dose

If you missed a dose of Nerlynx, don’t try to double up to take more than one dose at a time. Users should wait to take the following dose at the next scheduled time.

Overdose: What Happens If I Take Too Much Nerlynx?

If you accidentally took too much Nerlynx, your symptoms will depend on the amount that you took. Although the following symptoms are very similar to Nerlynx’s common side effects, they might be more severe:

• Dehydration
• Diarrhea
• Nausea and vomiting
• Stomach pain

If you took too many Nerlynx tablets, seek immediate medical attention.

Precautions

What Are Reasons I Shouldn't Take Nerlynx?

There are no contraindications to taking Nerlynx. A contraindication is anything (including a symptom or medical condition) that is a reason for a person to not receive a particular treatment or procedure because it may be harmful.

Depending on liver function and the severity of your symptoms—like diarrhea, however, your healthcare provider may consider completely stopping Nerlynx.

Additionally, this medication is not recommended during pregnancy due to potential harm to the unborn baby.

What Medications May Interact With Nerlynx?

If you take the following medications, the manufacturer might recommend either avoiding or adjusting Nerlynx:

• Antacids: Antacids—like Tums (calcium carbonate) are used for quick relief of mild heartburn symptoms. Puma Biotechnology recommends taking Nerlynx three hours after antacids.
• H2-receptor antagonists: H2-receptor antagonists are also known as H2-blockers. They are typically used to relieve occasional heartburn. An example of an H2-blocker is Pepcid AC (famotidine). The manufacturer recommends taking Nerlynx two hours before or 10 hours after H2-blockers.
• Medications that are P-glycoprotein (P-gp) substrates: P-gp is a type of transporter that moves some medications around in the body. If you take medication—like digoxin—that uses P-gp, there is a higher risk for side effects, such as toxicity to the heart. So, close monitoring is recommended.
• Medications that are strong inhibitors of CYP3A4: CYP3A4 is a type of protein in the liver that helps break down Nerlynx. If you take medications that prevent CYP3A4 from working, then there will be higher amounts of Nerlynx in the body. This will also worsen the risk of side effects. Therefore, Puma Biotechnology recommends against using Nerlynx with strong CYP3A4-inhibiting medications.
• Medications that moderately block CYP3A4 and P-gp: Medications that block both CYP3A4 and P-gp will lead to higher amounts of Nerlynx in the body and affect how Nerlynx moves in the body. The manufacturer recommends avoiding taking Nerlynx with medications that block both CYP3A4 and P-gp.
• Strong or moderate CYP3A4-inducing medications: If you take a medication that encourages CYP3A4 to break down Nerlynx quickly, then the medication will not be as effective. So, the manufacturer recommends against combining Nerlynx with strong or moderate CYP3A4-inducing medications.
• Proton pump inhibitors (PPIs): PPIs are commonly used to treat persistent heartburn. Puma Biotechnology recommends avoiding Nerlynx with PPIs. Examples of PPIs include Nexium (esomeprazole) and Prilosec (omeprazole).

If you have any questions or concerns about these drug interactions, talk with your healthcare provider.

What Medications Are Similar?

There are many treatment options for breast cancer. Out of all the available choices, Nerlynx belongs to the kinase inhibitor medication class.

Kinase inhibitors that are also used to treat HER2+ breast cancer include:

• Tukysa (tucatinib)
• Tykerb (lapatinib)

Tukysa and Tykerb are only used in people with HER2+ breast cancer that has advanced or spread. Nerlynx, on the other hand, can be used in HER2+ EBC or advanced HER2+ breast cancer.

In fact, per a 2020 study, the data suggested that the Nerlynx and Xeloda combination is better than the Tykerb plus Xeloda combination at preventing the worsening of metastatic HER2+ breast cancer.

Additionally, compared to Tukysa, Nerlynx is conveniently taken by mouth once a day. Tukysa is taken by mouth twice daily.

Since all of these meds are kinase inhibitors used to treat HER2+ breast cancer, they are not usually taken together. If you have any questions, please discuss them with your healthcare provider.

How Can I Stay Healthy While Taking Nerlynx?

After receiving a diagnosis of breast cancer from your healthcare provider, you might experience a variety of emotions.

Breast cancer treatments may also take a toll on your mind and body. A strong social support network—including family, friends, and support groups—may help. Also, consider a mental health professional.

Healthy lifestyle choices—including a healthy diet and exercise—may help improve self-esteem and body image.

A healthy lifestyle may also lower the risk of cancer coming back after treatment.