Olaparib

Skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

• Lynparza^®

Dosage Forms & Strengths

tablet

• 100mg
• 150mg

capsule

• 50mg

Ovarian Cancer

Do not substitute olaparib tablets with olaparib capsules on a mg-to-mg basis due to differences in the dosing and bioavailability of each formulation

Maintenance treatment of recurrent ovarian cancer

• Indicated for maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy
• Tablets: 300 mg (two 150-mg tablets) PO BID
• Continue treatment until disease progression or unacceptable toxicity

Advanced BRCA-mutated ovarian cancer

• Indicated as monotherapy for deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer in patients who have been treated with ≥3 prior lines of chemotherapy
• Tablets: 300 mg (two 150-mg tablets) PO BID
• Capsules: 400 mg (eight 50-mg capsules) PO BID
• Continue treatment until disease progression or unacceptable toxicity

Dosage Modifications

Management of adverse reactions

• Consider dose interruption or dose reduction to manage adverse reactions
• Tablets
  • Recommended dose reduction: 250 mg (one 150-mg tablet and one 100-mg tablet) PO BID
  • If a further final dose reduction is required, then reduce to 200 mg (two 100-mg tablets) PO BID
• Capsules
  • Recommended dose reduction: 200 mg (four 50-mg capsules) PO BID
  • If a further final dose reduction is required, then reduce to 100 mg (two 50-mg capsules) PO BID

Coadministration with CYP3A inhibitors

• Strong and moderate CYP3A inhibitors: Avoid use and consider other agents
• Tablets
  • If strong CYP3A inhibitors cannot be avoided: Reduce olaparib dose to 100 mg (one 100-mg tablet) PO BID
  • If moderate CYP3A inhibitors cannot be avoided: Reduce olaparib dose to 150 mg (one 150-mg tablet) PO BID
• Capsules
  • If strong CYP3A inhibitors cannot be avoided: Reduce olaparib dose to 150 mg (three 50-mg capsules) PO BID
  • If moderate CYP3A inhibitors cannot be avoided: Reduce olaparib dose to 200 mg (four 50-mg capsules) PO BID

Hepatic impairment

• Not studied
• No data in patients with baseline hepatic impairment (serum bilirubin >1.5 xULN)

Renal impairment

• Preliminary data show a 1.5-fold increase in mean exposure (AUC) with mild renal impairment (CrCl 50-80 mL/min) compared with normal renal function (CrCl >80 mL/min)
• Mild (CrCl 50-80 mL/min): No dose adjustment to the starting dose is required, but patients should be monitored closely for toxicity
• Tablets
  • Moderate (CrCl 31-50 mL/min): Reduce dose to 200 mg (two 100-mg tablets) BID
  • Severe (CrCl <30 mL/min or dialysis): Not evaluated
• Capsules
  • Moderate (CrCl 31-50 mL/min): Reduce dose to 300 mg BID
  • Severe (CrCl <30 mL/min or dialysis): Not evaluated

Dosing Considerations

Information on FDA-approved test for the detection of BRCA mutations is available at http://www.fda.gov/companiondiagnostics

Not indicated

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• wheezing, shortness of breath, new or worsening cough;
• severe or ongoing nausea or vomiting;
• blood in your urine or stools; or
• fever, weight loss, weakness, tiredness, easy bruising or bleeding, or other signs of infection.

Common side effects may include:

• signs of infection;
• feeling weak or tired;
• heartburn, indigestion, stomach pain, loss of appetite;
• nausea, vomiting, diarrhea;
• headache, back pain, muscle or joint pain;
• altered sense of taste;
• abnormal kidney function tests;
• rash; or
• cold symptoms such as stuffy or runny nose, sneezing, cough, sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Olaparib is a prescription medication used to treat women with advanced ovarian cancer associated with defective BRCA genes, as detected by an FDA-approved test.

Olaparib is a poly ADP-ribose polymerase (PARP) inhibitor that blocks enzymes involved in repairing damaged DNA. Olaparib kills cancer cells.

This drug is intended for women with heavily pretreated ovarian cancer that is associated with defective BRCA genes.

This medication comes in capsule form and is taken 2 times a day. Do not chew, divide, or break olaparib capsules. Swallow the capsules whole.

Common side effects of olaparib include nausea, fatigue, vomiting, and diarrhea.

Olaparib can also cause dizziness. Do not drive or operate heavy machinery until you know how olaparib affects you.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X - are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Olaparib falls into category D. It has been shown that use of olaparib in pregnant women caused some babies to be born with problems. However, in some serious situations, the benefit of using this medication may be greater than the risk of harm to the baby.

If you take too much olaparib, call your healthcare provider or local Poison Control Center or seek emergency medical attention right away.

If olaparib is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

• Store olaparib at room temperature.
• Keep this and all medications out of the reach of children.

Your doctor will perform a blood test to make sure olaparib is the right treatment for your condition.

Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Do not crush, chew, dissolve, or break an olaparib capsule or tablet. Swallow the pill whole.

If your doctor changes your brand, strength, or type of olaparib, your dosage needs may change. Ask your pharmacist if you have any questions about the olaparib pills you receive at the pharmacy.

Olaparib capsules must not be used as a substitute for olaparib tablets. These two pill forms are not taken in the same dosage amounts.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Olaparib can lower blood cells that help your body fight infections and help your blood to clot. You will need weekly or monthly blood tests. You may also need chest x-rays to be sure this medicine is not causing harmful effects on your lungs. Your cancer treatments may be delayed based on the results of these tests.

Store at room temperature away from moisture and heat.

Do not use any olaparib capsule that has been exposed to high heat (higher than 104 degrees).

Ovarian Cancer

Single-agent therapy for the treatment of confirmed or suspected deleterious germline BRCA-mutated (as detected by an FDA-approved companion diagnostic test [BRACAnalysis CDx]) advanced ovarian cancer previously treated with ≥3 chemotherapy regimens1 2 8 (designated an orphan drug by FDA for this use).3

Accelerated approval based on objective response rate and duration of response.1 6 7 9 14 Continued approval may be contingent on verification and description of clinical benefit in confirmatory studies.1 6 9

Women with mutations that result in defective BRCA genes are more likely to develop ovarian cancer.14 Approximately 10–15% of all cases of ovarian cancer appear to be associated with these hereditary BRCA mutations.14

Storage

Oral

25°C (may be exposed to 15–30°C); avoid exposure to temperatures >40°C (see Administration under Dosage and Administration).1

In the U.S.

• Lynparza

Available Dosage Forms:

• Capsule

Medicines used to treat cancer are very strong and can have many side effects. Before using olaparib, make sure you understand all the risks and benefits. It is important for you to work closely with your doctor during your treatment.

Take olaparib exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects.

olaparib usually comes with a Medication Guide. Read and follow the instructions carefully. Ask your doctor if you have any questions.

Swallow the capsules whole. Do not crush, break, chew, open, or dissolve them. Do not take capsules if they look damaged or have a leakage. You may take olaparib with or without food.

Do not eat grapefruit or Seville oranges, or drink grapefruit juice while you are using olaparib.

Dosing

The dose of olaparib will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of olaparib. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (capsules):
  • For advanced ovarian cancer:
    • Adults—400 milligrams (mg) (eight 50 mg capsules) 2 times a day. Each dose should be taken 12 hours apart. Your doctor may adjust your dose as needed.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of olaparib, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

• It is used to treat ovarian cancer.
• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Back pain.
• Hard stools (constipation).
• Not hungry.
• Dizziness.
• Headache.
• Heartburn.
• Muscle or joint pain.
• Nose or throat irritation.
• Change in taste.
• Feeling tired or weak.
• Mouth irritation or mouth sores.
• Signs of a common cold.
• Flu-like signs.
• It is common to have diarrhea, upset stomach, throwing up, or stomach pain with olaparib. Call your doctor if any of these side effects get very bad, bother you, or do not go away.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• AZD2281
• KU-0059436
• PARP Inhibitor AZD2281

Capsules: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Do not expose capsules to temperatures >40°C (104°F).

Tablets: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture.

Applies to olaparib: oral capsule, oral tablet

Oncologic

Uncommon (0.1% to 1%): Myelodysplastic syndrome/Acute Myeloid Leukemia[Ref]

Hematologic

Very common (10% or more): Decreased hemoglobin (up to 90%), elevated mean corpuscular volume (up to 85%), decreased lymphocytes (up to 56%), anemia (up to 34%), decreased absolute neutrophil count (up to 32%), decreased platelets (up to 30%)
Common (1% to 10%): Leukopenia[Ref]

Respiratory

Very common (10% or more): Nasopharyngitis/pharyngitis/upper respiratory infection (up to 43%), cough (up to 21%), dyspnea
Common (1% to 10%): Pulmonary embolism
Uncommon (0.1% to 1%): Pneumonitis[Ref]

Gastrointestinal

Very common (10% or more): Nausea (up to 75%), abdominal pain/discomfort (up to 47%), vomiting (up to 43%), diarrhea (up to 31%), dyspepsia (up to 25%), constipation
Common (1% to 10%): Stomatitis[Ref]

Other

Very common (10% or more): Fatigue/asthenia/lethargy (up to 68%), peripheral edema
Common (1% to 10%): Pyrexia[Ref]

Renal

Very common (10% or more): Increased creatinine (up to 30%)[Ref]

Musculoskeletal

Very common (10% or more): Arthralgia/musculoskeletal pain (up to 32%), myalgia (up to 25%), back pain (up to 25%)[Ref]

Cardiovascular

Common (1% to 10%): Hypertension, hot flush, venous thrombosis[Ref]

Dermatologic

Very common (10% or more): Dermatitis/rash (up to 25%)
Common (1% to 10%): Dry skin, eczema, pruritus[Ref]

Genitourinary

Very common (10% or more): Urinary tract infection
Common (1% to 10%): Dysuria, urinary incontinence, vulvovaginal disorder[Ref]

Metabolic

Very common (10% or more): Decreased appetite (up to 25%)
Common (1% to 10%): Hypomagnesemia, hyperglycemia[Ref]

Nervous system

Very common (10% or more): Headache (up to 25%), dysgeusia (up to 21%), dizziness
Common (1% to 10%): Peripheral neuropathy[Ref]

Psychiatric

Common (1% to 10%): Anxiety, depression, insomnia[Ref]

Some side effects of olaparib may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Initial dose: 400 mg (eight 50 mg capsules) orally twice a day
Duration of therapy: Continue treatment until disease progression or unacceptable toxicity

Comments: Patients should be selected based on the presence of deleterious or suspected deleterious germline BRCA-mutations, as detected by an approved test.

Use: Monotherapy in patients with deleterious or suspected deleterious germline BRCA mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy