TAKING COPIKTRA

COPIKTRA is one capsule taken twice daily by mouth, with or without food.

Take COPIKTRA exactly the way your doctor tells you
Take COPIKTRA two times a day
Swallow COPIKTRA capsules whole
Do not open, break, or chew your COPIKTRA capsules

Your doctor may change your dosing of COPIKTRA or tell you to stop taking COPIKTRA. Do not change your dose or stop taking COPIKTRA without talking to your doctor first.

What if I forget to take COPIKTRA?

If you miss a dose of COPIKTRA and it has been:

Less than 6 hours since your regular time:

Take the missed dose right away
Take the next dose as usual

More than 6 hours since your regular time:

Wait and take the next dose at your usual time

If you take too much COPIKTRA, call your doctor right away or go to the nearest hospital emergency room.

Before taking Copiktra

Before taking COPIKTRA, tell your healthcare provider about all of your medical conditions, including if you:

have intestinal problems
have lung or breathing problems
have an infection
are pregnant or plan to become pregnant. COPIKTRA can harm your unborn baby.
- Your healthcare provider should do a pregnancy test to see if you are pregnant before you start treatment with COPIKTRA.
- Females who are able to become pregnant should use effective birth control (contraception) during treatment with COPIKTRA and for at least 1 month after the last dose of COPIKTRA. Talk to your healthcare provider about birth control methods that may be right for you. Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment with COPIKTRA.
- Males with female partners who are able to become pregnant should use effective birth control (contraception) during treatment with COPIKTRA and for at least 1 month after the last dose of COPIKTRA.
are breastfeeding or plan to breastfeed. It is not known if COPIKTRA passes into breast milk. Do not breastfeed during treatment and for at least 1 month after the last dose of COPIKTRA.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. COPIKTRA and certain other medicines may affect each other.

Tips for remembering to take COPIKTRA

Record each dose in a treatment journal or on a calendar
Build a routine and take your medication at the same time each day
Take your medication before or after an activity that you do every day, like brushing your teeth
Set alarms on smartphones or watches
Have a family member or friend remind you

The COPIKTRA packaging can help you track your treatment.

COPIKTRA packaging is designed to help you remember to take your treatment two times a day, every day.

Use the weekday markers to track each day, and the AM and PM markers to track each dose.

How should I store Copiktra?

Store COPIKTRA at room temperature between 68°F to 77°F (20°C to 25°C).
Keep COPIKTRA in its original container until you are ready to take your dose.

Keep COPIKTRA and all medicines out of the reach of children.

IMPORTANT SAFETY INFORMATION

Treatment-related mortality occurred in 15% of COPIKTRA treated patients.
Fatal and/or serious infections occurred in 31% (4% fatal) of COPIKTRA-treated patients. Monitor for signs and symptoms of infection. Withhold COPIKTRA if infection is suspected.
Fatal and/or serious diarrhea or colitis occurred in 18% (<1% fatal) of COPIKTRA-treated patients. Monitor for the development of severe diarrhea or colitis. Withhold COPIKTRA.
Fatal and/or serious cutaneous reactions occurred in 5% (<1% fatal) of COPIKTRA-treated patients. Withhold COPIKTRA.
Fatal and/or serious pneumonitis occurred in 5% (<1% fatal) of COPIKTRA-treated patients. Monitor for pulmonary symptoms and interstitial infiltrates. Withhold COPIKTRA.

WARNINGS AND PRECAUTIONS

Treatment-related Mortality: In a randomized controlled study in patients with relapsed or refractory CLL or SLL, treatment with COPIKTRA caused increased treatment-related mortality. With extended follow-up with a median of 63 months, treatment-related deaths occurred in 15% (23/158) of those patients in the overall population. In the indicated patient population, patients with relapsed or refractory CLL or SLL after at least two prior lines of systemic therapy, treatment related deaths following treatment with COPIKTRA occurred in 14% (13/93) of patients. The most common cause of the treatment-related deaths were infections, which occurred in 9% and 11% of patients with relapsed or refractory CLL following at least one or two prior systemic therapies, respectively. COPIKTRA is not indicated and is not recommended for any patients in the initial or second-line treatment setting.

Infections: Serious, including fatal (18/442, 4%), infections occurred in 31% of patients receiving COPIKTRA. The most common serious infections were pneumonia, sepsis, and lower respiratory infections. Median time to onset of any grade infection was 3 months, with 75% of cases occurring within 6 months. Treat infections prior to initiation of COPIKTRA. Advise patients to report new or worsening signs and symptoms of infection. Cases of Pneumocystis jirovecii pneumonia (PJP) (1%) and cytomegalovirus (CMV) reactivation/infection (1%) occurred in patients taking COPIKTRA. Provide prophylaxis for PJP during treatment and following completion of treatment until the absolute CD4+ T cell count is greater than 200 cells/μL. Consider prophylactic antivirals during COPIKTRA treatment to prevent CMV infection including CMV reactivation.

Diarrhea or Colitis: Serious, including fatal (1/442; 0.2%), diarrhea or colitis occurred in 18% of patients receiving COPIKTRA. Median time to onset of any grade diarrhea or colitis was 4 months, with 75% of cases occurring by 8 months. The median event duration was 0.5 months. Advise patients to report any new or worsening diarrhea.

Cutaneous Reactions: Serious, including fatal (2/442; 0.5%), cutaneous reactions occurred in 5% of patients receiving COPIKTRA. Fatal cases included drug reaction with eosinophilia and systemic symptoms (DRESS) and toxic epidermal necrolysis (TEN). Median time to onset of any grade cutaneous reaction was 3 months with a median event duration of 1 month. Presenting features for the serious events were primarily described as pruritic, erythematous, or maculo-papular. Less common presenting features include exanthem, desquamation, erythroderma, skin exfoliation, keratinocyte necrosis, and papular rash. Advise patients to report new or worsening cutaneous reactions.

Pneumonitis: Serious, including fatal (1/442; 0.2%), pneumonitis without an apparent infectious cause occurred in 5% of patients receiving COPIKTRA. Median time to onset of any grade pneumonitis was 4 months with 75% of cases occurring within 9 months. The median event duration was 1 month with 75% of cases resolving by 2 months.

Hepatotoxicity: Grade 3 and 4 ALT and/or AST elevation developed in 8% and 2%, respectively, of patients receiving COPIKTRA (N=442). Two percent of patients had both an ALT or AST > 3 X ULN and total bilirubin > 2 X ULN. Median time to onset of any grade transaminase elevation was 2 months with a median event duration of 1 month. Monitor hepatic function during treatment with COPIKTRA.

Neutropenia: Grade 3 or 4 neutropenia occurred in 42% of patients receiving COPIKTRA (N=442), with Grade 4 neutropenia occurring in 24% of all patients. Median time to onset of grade ≥3 neutropenia was 2 months. Monitor neutrophil counts at least every 2 weeks for the first 2 months of COPIKTRA therapy, and at least weekly in patients with neutrophil counts < 1.0 Gi/L (Grade 3-4).

Embryo-Fetal Toxicity: COPIKTRA can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus and conduct pregnancy testing before initiating COPIKTRA treatment. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for 1 month after the last dose.

ADVERSE REACTIONS

B-cell Malignancies Summary

Fatal adverse reactions within 30 days of the last dose occurred in 8% (36/442) of patients treated with COPIKTRA 25 mg BID. Serious adverse reactions were reported in 289 patients (65%). The most frequent serious adverse reactions that occurred were infection (31%), diarrhea or colitis (18%), pneumonia (17%), rash (5%), and pneumonitis (5%). The most common adverse reactions (reported in ≥20% of patients) were diarrhea or colitis, neutropenia, rash, fatigue, pyrexia, cough, nausea, upper respiratory infection, pneumonia, musculoskeletal pain and anemia.

CLL/SLL

Fatal adverse reactions within 30 days of the last dose occurred in 12% (19/158) of patients treated with COPIKTRA and in 4% (7/155) of patients treated with ofatumumab. Serious adverse reactions were reported in 73% (115/158) of patients treated with COPIKTRA and most often involved infection (38%; 60/158) and diarrhea or colitis (23%; 36/158). The most common adverse reactions with COPIKTRA (reported in ≥20% of patients) were diarrhea or colitis, neutropenia, pyrexia, upper respiratory tract infection, pneumonia, rash, fatigue, nausea, anemia and cough.

For specific information on the management of the adverse reactions above, please review Dose Modifications for Adverse Reactions within the full Prescribing Information.

DRUG INTERACTIONS

CYP3A4 Inducers: Coadministration with a strong or moderate CYP3A inducer may reduce COPIKTRA efficacy. Avoid coadministration with strong or moderate CYP3A4 inducers.

CYP3A4 Inhibitors: Coadministration with a strong CYP3A4 inhibitor may increase the risk of COPIKTRA toxicities. Reduce COPIKTRA dose when coadministered with a strong CYP3A4 inhibitor.

CYP3A4 Substrates: Coadministration of COPIKTRA with sensitive CYP3A4 substrates may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A4 substrate.

Please see accompanying full Prescribing Information, including Boxed Warning.

To report Adverse Reactions during use of COPIKTRA, contact Secura Bio, call 1-844-9Secura or 1-844-973-2872 and/or to FDA at www.fda.gov/medwatch or call 1-800-FDA-1088.

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