Calquence

Calquence (acalabrutinib) is a targeted cancer treatment used for chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL), in certain patients.

Calquence is a Bruton tyrosine kinase (BTK) inhibitor that works by blocking BTK, a protein that plays a key role in cancer cell growth and division. By inhibiting BTK, Calquence helps to slow the progression of cancer and helps extend patients' lives

Calquence capsules and tablets are taken twice daily.

Calquence FDA approval was granted on October 31, 2017, for treating MCL. Its approval was later expanded to include CLL and SLL. Calquence is manufactured by AstraZeneca Pharmaceuticals.

Some cancer cells get signals to grow and divide from a protein called Bruton tyrosine kinase (BTK). The Calquence mechanism of action is by blocking Bruton tyrosine kinase (BTK), which helps to stop cancer cells from growing and multiplying, to help reduce cancer growth. The Calquence class of medications is called BTK inhibitors and is a targeted therapy.

Is Calquence chemotherapy?

No, Calquence is not chemotherapy; it is a targeted therapy, specifically a Bruton's tyrosine kinase (BTK) inhibitor.

Calquence is used for adult patients with:

• chronic lymphocytic leukemia (CLL)
• small lymphocytic lymphoma (SLL)
• mantle cell lymphoma (MCL) in patients are ineligible for autologous hematopoietic stem cell transplantation (HSCT), and used in combination with bendamustine and rituximab.

Calquence directions

• Calquence tablets and capsules are usually taken twice per day (about 12 hours apart) with or without food, with a glass of water. Swallow the tablet and capsule whole, and do not crush, chew, break, open, or dissolve them.
• If you need to take an antacid medicine, take it either 2 hours before or 2 hours after you take Calquence. If you need to take certain other medicines called acid reducers (H-2 receptor blockers), take Calquence 2 hours before the acid reducer medicine.
• Your healthcare provider may tell you to decrease your dose, temporarily stop, or completely stop taking this medicine if you develop certain side effects.
• Take this medicine exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose.
• If you need surgery, tell the surgeon beforehand that you are using this medication. You may need to stop using the medicine for a short time.
• While taking this medicine, you may need frequent blood tests.
• If you've had hepatitis B, it may come back. You may need liver function tests while using this medicine.

Bleeding problems. Calquence can make it easier for you to bleed. Contact your doctor or seek emergency medical attention if you have any bleeding that will not stop.

Call your doctor at once if you have signs of bleeding inside your body, such as: dizziness, weakness, confusion, headache, speech problems, black or bloody stools, pink or brown urine, or coughing up blood or vomit that looks like coffee grounds.

Your healthcare provider may stop this medicine for any planned medical, surgical, or dental procedure

Infections: Monitor for signs and symptoms of infection and treat promptly.

Change in blood tests. It may cause low levels of red blood cells (anemia), white blood cells (leukopenia), or platelets (thrombocytopenia). You will have complete blood counts regularly.

Second Primary Cancer: Other cancers have occurred, including skin cancers and other solid tumors. Always use sun protection.

Heart rhythm changes: You will be monitored for symptoms of problems with the rate or rhythm of your heart (arrhythmias).

Severe hepatic impairment. This medicine should be avoided in patients with severe liver impairment and liver problems that have occurred in patients taking this medicine. If you have symptoms of stomach pain, dark-colored urine of dark color, or yellowing of your skin, you should contact your healthcare provider, who will monitor your liver function.

To make sure Calquence is safe for you, tell your doctor if you have ever had:

• an active or chronic infection, including hepatitis B;
• a heart rhythm disorder;
• bleeding problems;
• recent surgery or plan to have surgery, medical or dental procedure; or
• liver problems

Taking Calquence may increase your risk of developing other cancers. Ask your doctor about this risk.

Pregnancy

Tell your healthcare professional if you are pregnant or plan to become pregnant, as Calquence may harm your unborn baby and problems during childbirth (dystocia). Your healthcare provider may do a pregnancy test before you start treatment, if you are able to become pregnant.

Females who are able to become pregnant should use effective birth control (contraception) during treatment with this medicine and for at least 1 week after the last dose.

Breastfeeding

Tell your healthcare professional if you are breastfeeding or plan to breastfeed. It is not known if Calquence passes into your breast milk. Do not breastfeed during treatment with this medicine and for at least 2 weeks after your final dose.

Common Calquence side effects

Common Calquence side effects include:

• Infection (65%)
• Upper respiratory tract infection - URTI (35%)
• Lower respiratory tract infection - LRTI (18%)
• Urinary tract infection - UTI (15%)
• Headache (39%)
• Dizziness (20%)
• Diarrhea (35%)
• Nausea (22%)
• Musculoskeletal pain (32%)
• Joint pain (16%)
• Tiredness (23%)
• Bruising (21%)
• Rash (25%)
• Hemorrhage (20%).

There were also changes in blood test levels neutropenia 23% (low white blood cells), anemia 53% (low red blood cells), thrombocytopenia 32% (low platelet levels, and lymphocytosis 16% (high white blood cells).

The above common side effects occurred in patients being treated with Calquence CLL as monotherapy and occurred in 15% or more of patients.

Serious side effects

Calquence may cause serious side effects. Call your doctor at once if you have:

• unusual bleeding - nosebleeds, bleeding gums, abnormal vaginal bleeding, any bleeding that will not stop
• bleeding inside your body - weakness, dizziness, confusion; problems with speech, prolonged headache, bloody or tarry stools, pink or brown urine; coughing up blood or vomit that looks like coffee grounds
• heart rhythm disorders - dizziness, chest pain, shortness of breath, fast or irregular heart rate, or feeling light-headed. Serious cardiac arrhythmias have occurred in patients treated with Calquence
• low blood cell counts - fever, chills, tiredness, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands and feet, feeling light-headed or short of breath
• signs of infection - fever, chills, tiredness, flu-like symptoms, cough with mucus, chest pain, trouble breathing.

Get emergency medical help if you have signs of an allergic reaction to Calquence hives, difficulty breathing, or swelling of your face, lips, tongue, or throat.

This medicine may cause a brain infection that can lead to disability or death. Tell your doctor if you have problems with speech, thought, vision, or muscle movement. These symptoms can get worse quickly.

Liver toxicity, which may be severe or fatal, has been reported with Bruton tyrosine kinase inhibitors, including this medicine. Your healthcare provider will monitor your liver function tests before starting treatment with this medicine and while you are taking it. Tell your healthcare provider immediately if you experience abdominal discomfort, dark urine, or yellowing of the skin.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

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 the FDA at 1-800-FDA-1088.

Usual monotherapy adult dose of Calquence for CLL, SLL, or MCL

Dose: Calquence 100 mg capsule or tablet orally every 12 hours until the cancer progresses or there is unacceptable toxicity.

Usual adult dose in combination with obinutuzumab

For patients with previously untreated CLL or SLL. The recommended dose of Calquence 100 mg taken orally approximately every 12 hours. Start Calquence at Cycle 1 (each cycle is 28 days). Start obinutuzumab (Gazyva) at Cycle 2 for a total of 6 cycles and refer to the obinutuzumab prescribing information for recommended dosing.

Administer Calquence before obinutuzumab when given on the same day.

Usual adult Calquence dose in combination with bendamustine and rituximab

For patients with previously untreated MCL. The recommended dosage of 100 mg is taken orally approximately every 12 hours until disease progression or unacceptable toxicity

Start Calquence on Day 1 of Cycle 1 (each cycle is 28 days)

Administer bendamustine 90 mg/m2 on Days 1 and 2 and rituximab 375 mg/m2 on Day 1 of Cycle 1 and continue for a total of 6 cycles.

Patients achieving a response (PR or CR) after the first 6 cycles may receive maintenance rituximab on Day 1 of every other cycle for a maximum of 12 additional doses, starting on Cycle 8 up to Cycle 30

Usual adult Calquence dose in combination with Venetoclax

For patients with previously untreated CLL or SLL, the recommended dosage of Calquence is:

• 100 mg taken orally approximately every 12 hours until disease progression, unacceptable toxicity, orcompletion of 14 cycles of treatment.
• Start Calquence at Cycle 1 (each cycle is 28 days).
• Start venetoclax at Cycle 3 for a total of 12 cycles.
• Start venetoclax at 20 mg daily for the first week of treatment and increase weekly as per dosing schedule for 5-week ramp up (up to 400 mg daily) as described in the venetoclax USPI.

General dose information

How long do you take Calquence? Calquence treatment should be continued until the cancer progresses or there is unacceptable toxicity.

Formulations available:

• Calquence 100mg capsules.
• Calquence 100mg tablets.

Hepatic Impairment. You should not take this medicine if you have severe hepatic impairment. Dose modifications are not required for patients with mild or moderate hepatic impairment.

Dose modifications for drug interactions. See detailed dosing information for dose modifications required for drug interactions.

Take the medicine as soon as you can, but skip the missed dose if you are more than 3 hours late for the dose. Do not use two doses at one time.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Avoid taking an antacid such as Tums or calcium carbonate within 2 hours before or after you take Calquence.

Calquence could make you sunburn more easily. Avoid sunlight or tanning beds. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

Sometimes it is not safe to use certain medicines at the same time. Some drugs can affect your blood levels of other drugs you use, which may increase side effects or make the medicines less effective.

Drug interactions with groups:

• Strong CYP3A Inhibitors: Avoid co-administration of strong CYP3A Inhibitors with Calquence.
• Moderate CYP3A Inhibitors: Reduce the dosage of Calquence if these medicines are used together.
• Strong CYP3A Inducers: Avoid co-administration of strong CYP3A Inducers with Calquence. If co-administration is unavoidable, then the dosage of Calquence should be increased.

If you use a stomach acid reducer such as cimetidine, ranitidine, Tagamet, Pepcid, or Zantac, take the Calquence dose 2 hours before taking any of these other medicines.

Tell your doctor about all your current medicines. Many drugs can affect acalabrutinib, especially:

• a blood thinner (warfarin, Coumadin, Jantoven);
• an antibiotic or antifungal medicine (itraconazole, fluconazole, erythromycin, rifampin);
• antiviral medicine to treat hepatitis C or HIV/AIDS;
• heart medication (diltiazem); or
• a proton pump inhibitor stomach acid medicine - such as omeprazole, lansoprazole, rabeprazole, Nexium, Prevacid, Prilosec, Protonix, and others.

This list is not complete and many other drugs may interact with acalabrutinib. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.

The Calquence Copay Card can help you pay as little as $0 per month for out-of-pocket costs if you have commercial insurance plans.

AstraZeneca has a support program called AstraZeneca Access 360, which can help with questions about insurance, costs, affordability options, and other patient resources.

For patients with Medicare or no insurance facing affordability challenges, there is also an AstraZeneca Prescriptions Savings plan called AZ&ME.

Links for Calquence Copay, Calquence Access 360 Co-pay, are on the Calquence Prices, Copay Cards & Patient Assistance page.

Review the Calquence Package Insert (PI) for more detailed information about this medicine. The PI contains more comprehensive information on Indications and Usage, Dosage and Administration, Clinical Pharmacology, Clinical Studies, Drug Interaction, and more. Discuss any medical questions you have with your doctor or other health care provider. This is not all the information you need to know about this medicine for safe and effective use, and it does not take the place of talking to your doctor about your treatment.

The Package Insert is sometimes called Calquence Prescribing Information (PI) or FDA label

Active ingredient: acalabrutinib

Capsule inactive ingredients

• silicified microcrystalline cellulose, pregelatinized starch, magnesium stearate, and sodium starch glycolate.
• Capsule shell contains: gelatin, titanium dioxide, yellow iron oxide, FD&C Blue 2, and black ink.

Tablet Inactive ingredients:

• Tablet core: low-substituted hydroxypropyl cellulose, mannitol, microcrystalline cellulose, and sodium stearyl fumarate.
• Tablet coating: copovidone, ferric oxide yellow, ferric oxide red, hypromellose, medium-chain triglycerides, polyethylene glycol 3350, purified water, and titanium dioxide.

Calquence AstraZeneca Pharmaceuticals LP: Wilmington, DE 19850, USA.