PARP inhibitors: Uses, common brands, and safety info, poly-ADP ribose polymerase

PARP inhibitors are a class of drugs used for cancer treatment known as a type of targeted cancer therapy. Targeted cancer therapies are drugs that block the growth and spread of cancer. Targeted therapies do this by interfering with certain molecules that help cancer grow and spread. 

Although targeted therapies are used in cancer, they are different from standard chemotherapy. For example, one difference is that targeted therapy acts on specific targets (cancer cells), while most chemotherapies act on both normal and cancer cells. There are many targeted therapies approved by the U.S. Food and Drug Administration (FDA) for certain types of cancer. Other targeted therapies are still being studied in cancer research clinical trials.

This article will provide general information about PARP inhibitors, including uses, common brand names, and safety information. The PARP inhibitors are listed in the chart below. 

Other PARP inhibitors

Veliparib is a PARP inhibitor that is currently being investigated to treat breast cancer and ovarian cancer. It is not available yet. 

Other clinical trials related to PARP inhibitors can be found on clinicaltrials.gov.

What are PARP inhibitors?

PARP inhibitors are known as a type of treatment called targeted therapy. PARP stands for poly ADP-ribose polymerase. This is a group of enzymes that help fix DNA damage. PARP1, PARP2, and PARP3 are enzymes that work together to help repair damaged DNA. PARP inhibitors block PARP. PARP inhibition prevents cancer cells from repairing their damaged DNA. This causes death of tumor cells. 

How do PARP inhibitors work?

PARP enzymes help fix damaged DNA. BRCA genes (BRCA1 and BRCA2) also play a role in DNA repair through another pathway. When there is a BRCA mutation, the pathway to DNA repair is blocked. PARP inhibitors block the PARP pathway. This makes it hard for cancer cells with abnormal BRCA genes to fix damaged DNA. When the DNA in cancer cells cannot repair itself, these cells die. PARP inhibitors block DNA from being repaired, and as a result, the cells die. 

What are PARP inhibitors used for?

Each PARP inhibitor has specific indications. PARP inhibitors are used alone or in combination with other cancer treatments, typically after traditional chemotherapy (such as with carboplatin) has been used. 

Lynparza is used for ovarian cancer, fallopian tube cancer, peritoneal cancer, breast cancer, prostate cancer, and pancreatic cancer, more specifically:

• First-line maintenance treatment of BRCA-mutated advanced ovarian, fallopian tube, or primary peritoneal cancer

• First-line maintenance treatment of homologous recombination deficiency (HRD)-positive advanced ovarian, fallopian tube, or primary peritoneal cancer in combination with bevacizumab

• Maintenance treatment of recurrent ovarian cancer

• Advanced germline (inherited) BRCA-mutated ovarian cancer after three or more lines of chemotherapy

• Germline BRCA-mutated HER2-negative metastatic breast cancer

• First-line maintenance treatment of germline BRCA-mutated metastatic pancreatic adenocarcinoma

• HRR gene-mutated metastatic castration-resistant prostate cancer

Rubraca is used for ovarian cancer, fallopian tube cancer, peritoneal cancer, and prostate cancer, more specifically:

• Maintenance treatment of recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer

• BRCA mutation (germline and/or somatic)-associated epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who have received treatment with 2 or more chemotherapies

• Metastatic castration-resistant prostate cancer with BRCA mutations

Talzenna is used for breast cancer, more specifically:

• BRCA-mutated HER2-negative locally advanced or metastatic breast cancer

Zejula is used for ovarian cancer, fallopian tube cancer, or peritoneal cancer, more specifically:

• First-line maintenance treatment of advanced ovarian, fallopian tube, or primary peritoneal cancer

• Maintenance treatment of recurrent ovarian, fallopian tube, or primary peritoneal cancer

• Treatment of advanced ovarian, fallopian tube, or primary peritoneal cancer after treatment with 3 or more chemotherapies

Who can take PARP inhibitors?

A PARP inhibitor is not appropriate for everyone. Before taking a PARP inhibitor, talk to your doctor of oncology (oncologist) about your medical conditions and history. Some medical conditions require dosage adjustments.

Men

Men can take a PARP inhibitor, provided that they fall into one of the specific indicated categories, and that there are no contraindications to treatment. Also, a healthcare professional must determine if it will be an appropriate treatment. 

Women

Women who are not pregnant or breastfeeding can take a PARP inhibitor if they are in one of the specific indicated groups, and that there are no contraindications to treatment. The healthcare provider must also determine the appropriateness of treatment. 

Women who are pregnant or breastfeeding

PARP inhibitors carry a risk to the unborn baby and a potential for the loss of the pregnancy. Women who are pregnant or think they may be pregnant should tell their healthcare provider right away. Women of childbearing age should use effective contraception while being treated with a PARP inhibitor and for some time after the last dose. 

Discuss effective contraception with your healthcare professional. Men who take a PARP inhibitor and have a female partner of childbearing age should use effective contraception during treatment and for some time after the last dose. Men should not donate sperm during PARP inhibitor treatment and for some time after the last dose. 

Women should not breastfeed while taking a PARP inhibitor and for some time after the last dose. 

*The prescribing information specifies different time periods for each PARP inhibitor. Consult the prescribing information for more specific information.

Children

PARP inhibitors are not indicated for use in children. Safety and efficacy have not been determined in this age group. 

Older adults

PARP inhibitors have similar results in safety and efficacy in older adults and younger adults. However, the manufacturer information states that some older adults may have greater sensitivity to these medications. Consult your healthcare provider for medical advice. 

Are PARP inhibitors safe?

Recalls

There have been no recalls on PARP inhibitors.

Restrictions

Certain people cannot take PARP inhibitors. Before taking a PARP inhibitor, talk to your doctor. Tell your doctor about all of your medical conditions and medical history. PARP inhibitors interact with certain medications. Review your medications, including prescription and over-the-counter medicines and any vitamins or supplements you take. This will help your healthcare provider determine if a PARP inhibitor will be an appropriate drug for you. Your doctor will also perform a test to make sure the medication is right for you. 

People who are allergic to a PARP inhibitor or any of its ingredients should not take a PARP inhibitor. 

Other PARP inhibitor warnings include:

Patients should be frequently monitored for Myelodysplastic Syndrome (MDS; bone marrow disorder) and Acute Myeloid Leukemia (AML; a type of blood cancer). MDS and AML are rare but can be fatal. Symptoms include weakness, weight loss, fever, shortness of breath, fatigue, and easy bruising and bleeding. Bloodwork will be monitored before and drug treatment with a PARP inhibitor.

Pneumonitis (lung inflammation) is also rare and can be fatal. Tell your doctor if you have a fever, shortness of breath, coughing, or wheezing. If pneumonitis is suspected, PARP inhibitor treatment should be held. If pneumonitis is confirmed, treatment should be stopped. 

PARP inhibitors may cause fetal harm. Effective contraception should be used. (See section “Women who are pregnant or breastfeeding” for more information.)

Some cancer patients with metastatic castration-resistant prostate cancer have developed blood clots, including clots in the lung. Patients should be monitored for blood clots. Get medical treatment right away if you have pain or swelling in an extremity, shortness of breath, chest pain, or faster heart rate or breathing.

Additional warnings:

• Lynparza: Avoid grapefruit and Seville oranges as well as their juices (grapefruit juice and Seville orange juice) while taking Lynparza

• Rubraca: Use sun protection (wear sunscreen, a hat, and clothing to cover as much skin as possible) while taking Rubraca. Taking Rubraca increases the risk of sunburn 

• Talzenna: Talzenna may cause fertility problems in men

• Zejula: Zejula may increase heart rate and blood pressure. Your doctor will monitor your heart rate and blood pressure during treatment with Zejula. 

Posterior Reversible Encephalopathy Syndrome (PRES) has occurred in people who take Zejula. If you have headaches, confusion, seizure (may be accompanied by high blood pressure), or changes in vision, contact your doctor right away. Stop taking Zejula if PRES is confirmed. 

Zejula contains the color additive FD & C Yellow No. 5 (tartrazine). Tartrazine may cause allergic reactions in certain patients. 

Are PARP inhibitors controlled substances?

No, PARP inhibitors are not controlled substances.

Common PARP inhibitors side effects

Before taking a PARP inhibitor, talk to your doctor about potential side effects and how to address them. The most common side effects of PARP inhibitors are:

• Stomach problems

  • Nausea

  • Vomiting 

  • Diarrhea

  • Constipation

  • Indigestion

  • Stomach pain

• Tiredness

• Decreased red blood cells (anemia)

• Appetite loss

• Mouth sores 

• Altered taste

• Cough or respiratory infection

• Headache

• Dizziness

• Shortness of breath 

• Muscle or joint pain

• Swelling

• Rash

• Urinary tract infection

• Back pain

• Fever 

• Low magnesium levels

• Low white blood cell counts (lymphopenia, neutropenia, leukopenia)

• Low platelet count (thrombocytopenia)

• Blood clots in the veins (venous thromboembolism)

More serious side effects may occur. Some side effects can be both common and severe. Serious side effects of PARP inhibitors include:

• Thrombocytopenia 

• Leukopenia, lymphopenia, neutropenia (febrile neutropeniacan occur)

• Disruption of blood cell production (myelodysplastic syndrome)

• Anemia 

• Venous thromboembolism

• A blood clot that travels to the lungs (pulmonary embolism) 

• Blood infection (sepsis)

• Acute myelogenous leukemia (AML)

• Lung inflammation (pneumonitis)

• Shortness of breath

• Painful bumps under the skin, often on the shins (erythema nodosum)

Allergic reactions are rare but can be severe or life-threatening. If you are taking a PARP inhibitor and have signs of an allergic reaction such as hives, shortness of breath, difficulty breathing, or swelling of the lips, face, tongue, or throat, get emergency medical help immediately. 

Other side effects may occur. Consult your healthcare professional for a complete list of side effects. Report side effects to your doctor. 

How much do PARP inhibitors cost?

The price of PARP inhibitors varies by insurance plan. PARP inhibitors are usually filled at a specialty pharmacy. One study determined PARP inhibitor therapy to cost over $13,000, but with an average out-of-pocket cost of only $44. As insurance plans can change, contact your insurance provider to obtain pricing information or check SingleCare for PARP inhibitor coupons.