Olaparib: Dosage, Benefits, and Side Effects

What Is Olaparib?

Olaparib is a prescription drug. Your doctor will prescribe this drug if you are dealing with advanced ovarian, fallopian tube, prostate, or peritoneal cancer.

The FDA (the Food and Drug Administration) gave it the green light back in December 2014.

What Are the Available Dosage Forms and Strengths?

Olaparib is available as tablets. You can get Olaparib as tablets that come with a special coating.

You will find them in two different strengths: a 100 mg option (yellow to dark yellow) and a 150 mg option (green to green/grey).

For Patients:

How Does Olaparib Work?

Olaparib is a PARP (Poly (ADP-ribose) polymerase) inhibitor. It blocks this enzyme called PARP from doing its job. Now, if you have a BRCA1 (breast cancer) or BRCA2 mutation, you are unfortunately at a higher risk for certain cancers that are different from regular cancer types. These cancers don't respond well to your typical treatment approaches.

Cancer cells depend on that PARP enzyme to repair their DNA and survive. Olaparib comes in by blocking PARP, so we can essentially stop these cancer cells from repairing themselves. It is like cutting off their survival lifeline. That is why Olaparib plays such an essential role in treating these specific types of cancer.

What Is Olaparib Used for?

Olaparib is useful in the following situations.

• If you have already been through chemotherapy and you are at high risk of your cancer coming back, Olaparib could help, especially if you have early-stage, HER2-negative (human epidermal growth factor) breast cancer with a BRCA1 or BRCA2 mutation.

• If you have metastatic breast cancer with those same BRCA mutations and if you are HER2-negative and other treatments are not working anymore, this medication might be your next step.

• For those of you dealing with ovarian, fallopian tube, or peritoneal cancer, and if you have had a good response to chemotherapy (whether complete or partial), Olaparib can help you maintain that progress.

• If you are facing metastatic prostate cancer that has spread and is not responding to hormone therapy anymore, or if it has gotten worse after trying Enzalutamide or Abiraterone, your doctor might suggest Olaparib. Sometimes you will take it with other medicines too.

• And finally, if you have pancreatic cancer that has not spread or gotten worse after your first round of chemotherapy, Olaparib can help keep things stable.

How Is Olaparib Given?

• Your doctor will likely prescribe 300 mg.

• You will take these tablets by mouth twice a day.

• You can take them with or without food, whatever works for you.

• Make sure you swallow the tablet whole. Don't chew, crush, dissolve, or break it up.

• If you are being treated for metastatic castration-resistant prostate cancer (mCRPC ), which is the advanced stage of prostate cancer, you will need to take this along with a GnRH (gonadotropin-releasing hormone) analog to keep testosterone levels low, unless you have had both testicles surgically removed.

• If you have moderate kidney problems (your creatinine clearance is between 31 and 50 mL per minute), your doctor will probably lower your dose to 200 mg, still taken by mouth twice daily.

What Are the Important Warnings and Precautions?

The warnings and precautions associated with Olaparib are as follows:

Blood Disorders:

If you have blood disorders like myelodysplastic syndrome (MDS) (a group of blood cancers), where your blood cells get stuck in an immature state inside your bone marrow. They just won't grow up into the healthy cells your body needs. Acute myeloid leukemia (AML) is similar; it affects your white blood cells when they are still immature.

Studies show that about 1.5 % of people taking Olaparib develop MDS or AML. Unfortunately, some of these cases have been fatal. That is why your doctor will want to check your blood thoroughly before you start taking Olaparib. Once you are on it, you will need regular blood tests to keep tabs on how you are doing.

Lung Inflammation (Pneumonitis)

About 0.8 % of people on Olaparib develop pneumonitis (inflammation in your lung tissue). Some cases have been fatal. Watch for new symptoms such as coughing, trouble breathing, or fever. If you notice these, tell your doctor right away. They will probably want to do a chest X-ray to see what is going on.

Risks During Pregnancy

If you are pregnant or thinking about getting pregnant, Olaparib can seriously harm a developing baby. Animal studies have shown that it can damage organs as they are forming. So if you are trying to conceive, you will need to use reliable birth control and wait at least six months after your last dose before trying to get pregnant.

Blood Clot Risks

Olaparib can cause blood clots that might block blood flow to essential organs, especially your lungs (which is called a pulmonary embolism). This happens more often if you have metastatic castration-resistant prostate cancer and you are also getting androgen deprivation therapy along with Olaparib.

What Should Patients Tell the Doctor Before Treatment?

Before you start taking Olaparib, let your doctor know about any medical conditions you have. This is really important for your safety.

• Any breathing issues or lung problems you are dealing with.

• Kidney problems you might have.

• If you are pregnant or hoping to become pregnant soon.

• If you are currently breastfeeding.

• Don't forget to share your medication history too, which includes everything from prescription drugs to those daily vitamins you take or any herbal supplements you are using.

What Are the Side Effects of Olaparib?

Some of the common Olaparib side effects include:

• Nausea or vomiting.

• Dizziness.

• Loose stools.

• Reduction in blood cells (especially red blood cells).

• Taste alteration.

• Cough.

• Digestion issues.

• Heartburn.

• Lethargy.

Dietary Recommendation:

When you are taking Olaparib, you will want to pay attention to what you eat and how you take your medication. Certain fruits can mess with how the drug works in your body, so you will need to steer clear of those. You might also experience some tummy troubles as a side effect, which is totally normal, but something to keep in mind when planning your meals.

Missed Dose:

If you forget to take your Olaparib tablet when you are supposed to, don't try to make up for it by taking the missed dose when you remember. Doubling up can cause serious issues. Just skip that missed dose and take your next one at the regular time you have scheduled.

Overdose:

If you think you have taken too much Olaparib, don't wait; get yourself to a doctor or hospital right away. Your safety comes first, so reach out to a doctor immediately to prevent any serious problems. Remember, you should not take more than four Olaparib tablets in a single day. And if you are ever unsure about your dosage or how many pills you have taken, just consult your doctor.

How Should Olaparib Be Kept?

When storing your Olaparib, keep it in the container it came in. Make sure you store it at room temperature, between 68°F (Fahrenheit) and 77°F (or 20° to 25°Celsius).

Keep away from direct light, and definitely keep it out of reach of kids and pets. You need to protect your medication from any moisture, so don't transfer it into a pillbox. Just leave it in its original packaging.

For Doctors:

What Are the Pharmacological Actions of Olaparib?

1. Pharmacodynamics:

Researchers examined how your heart's electrical activity changes when you take Olaparib. They found that it does not mess with the QT interval at all. The heart rhythm stays just the way it should be.

• Chemical Taxonomy:

• • Superclass: Organic heterocyclic compounds.
  • Class: Diaz Naphthalenes.
  • Subclass: Benzodiazines.
  • Direct parent: Phthalazinones.

• Ingredients:

  • Active Ingredients: The only active ingredient present is Olaparib.
  • Inactive Ingredients: The inactive ingredients present in the tablet are:

    • Copovidone.

    • Mannitol.

    • Colloidal silicon dioxide.

    • Sodium stearyl fumarate.

The inactive ingredients present in the coating are:

• Hypromellose.

• Polyethylene glycol.

• Titanium dioxide.

• Ferric oxide yellow and ferrosoferric oxide.

2. Pharmacology:

• Absorption:

When you take Olaparib by mouth, your body absorbs it quickly. You will typically hit your peak blood levels in about an hour and a half. Your Olaparib levels go up steadily as you increase your dose from 25 mg to 450 mg. If you take it with a high-fat meal, your body absorbs it more slowly. You will reach your maximum concentration about 2.5 hours later than usual.

• Distribution:

When you take a single 300 mg dose of Olaparib, your body distributes it through about 158 liters of fluid (give or take 136 liters). As for how well it sticks to your proteins, you are looking at roughly 82 % binding efficiency.

• Metabolism:

When you take Olaparib, your body starts breaking it down through an oxidation process. After that happens, the broken-down pieces get paired up with glucuronide or sulfate. Your liver does most of the heavy lifting here. It uses special enzymes called cytochrome P450 (specifically CYP3A4 (cytochrome) or 5) to metabolize the drug. Your body changes most of the Olaparib you take. Only about 15 % leaves your body unchanged through your urine, and just 6 % exit unchanged in your stool. The rest of it is transformed into different compounds.

• Elimination:

When you take Olaparib, your body typically keeps it in your bloodstream for about 14.9 hours (give or take 8.2 hours) before half of it is gone. That is what we call the half-life.

If you take a single 300 mg dose, your body clears it from your plasma at a rate of roughly 7.4 liters per hour (plus or minus 3.9 L/hr). Your body breaks down most of the Olaparib you take into smaller metabolites before getting rid of them.

After about a week, researchers found that the body eliminates about 44% of the drug through the urine and another 42% through the stool.

• Toxicity:

There is no relevant information or evidence regarding the overdose or toxicity of Olaparib. The lethal dose (LD50 is the amount required to cause 50 % death in a given population) of Olaparib, found in rats, was 240 to 300 mg/kg.

What Are the Clinical Studies of Olaparib?

1. For Maintenance Treatment of Recurrent Ovarian Cancer:

• A double-blinded, placebo-controlled trial was undertaken in patients having gBRCAm ovarian, fallopian tube, or primary peritoneal cancer.

• The patients were randomly assigned to receive either 300 mg twice daily or a placebo.

• All the patients were treated earlier with platinum-based regimens.

• Results: The study concluded with a significant reduction in disease progression and an improvement in patient survival.

2. For Advanced gBRCA: Mutated Ovarian Cancer Treated With Prior Chemotherapy:

• 137 patients with advanced gBRCAm ovarian cancer were selected.

• All patients had received three or more prior lines of chemotherapy.

• Later, the patients were given 400 mg twice daily as a monotherapy.

• The overall response and efficacy improved significantly.

3. For Treatment of gBRCAm HER2-Negative Metastatic Breast Cancer:

• This study selected patients with gBRCAm HER2-negative metastatic breast cancer.

• All patients received a 300 mg dose of Olaparib.

• Results: There was a significant improvement in disease-free survival and overall survival in the olaparib arm compared with the chemotherapy arm.

What Are the Drug Interactions of Olaparib?

• When you are taking Olaparib along with other drugs that affect your bone marrow, you might notice more potent side effects on your blood cells.

• How does your body handle Olaparib? It is mainly broken down by something called CYP3A (cytochrome P450, family 3, subfamily A). Now, if you are taking medications that block CYP3A, they will cause Olaparib levels to build up in your system. Even everyday things like grapefruit, grapefruit juice, and Seville oranges can do this; they are strong CYP3A blockers.

• On the flip side, you will want to steer clear of drugs that boost CYP3A activity. Because they will lower the amount of Olaparib in your bloodstream, making it less effective.

How Does Olaparib Work for Different Populations?

• Olaparib During Pregnancy and Breastfeeding:

If you are pregnant or thinking about getting pregnant, you need to know that Olaparib can seriously harm your baby. It can cause birth defects (by messing with how your baby's organs develop) and even lead to miscarriage. That is why if you are taking Olaparib, you will need to use birth control during treatment and keep using it for at least six months after your last dose. And if you are breastfeeding, you will need to stop while you are on Olaparib and wait at least a month after finishing treatment before you start again.

• Olaparib in Kids:

Right now, there are no adequate clinical studies to show whether Olaparib is safe or effective in children.

• Olaparib in Older Adults:

Studies have not found any differences in the safety or effectiveness of Olaparib, whether you are younger or older.

• Olaparib if You Have Kidney Problems:

If you have mild kidney issues, you won't need to change your starting dose of Olaparib for breast cancer treatment. But if your kidney problems are moderate, your doctor will likely reduce your dose to 200 mg. Unfortunately, we don't have enough information yet about using Olaparib in case of severe kidney problems.

• Olaparib if You Have Liver Problems:

If you have mild liver issues, you can start with the regular dose of Olaparib.

Conclusion

Olaparib is a drug that your doctor gives if you are suffering from advanced types of cancer, like ovarian cancer, fallopian tube cancer and peritoneal cancer. This drug mainly kills cancer cells, but it spares your normal healthy cells. It is a personalized treatment approach, but it also has side effects, so care should be taken. This drug has increased the survival rate of cancer patients.

If you want to know more about this drug's safety and how to use this drug, you can consult a cancer specialist for proper guidance.

Key Takeaways

• Olaparib is a chemotherapy medicine for cancer treatment.

• Olaparib medication helps fight advanced cancers in your ovaries, peritoneum, fallopian tubes, and prostate by blocking an enzyme called PARP.

• You will typically take it as tablets, but you might feel tired or develop anemia as side effects.

• Severe side effects of Olaparib include lung infections, blood clotting, and acute myeloid leukemia.

• When you follow your doctor's instructions carefully, though, it can be really effective in treating these cancers.