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Duvelisib (Copiktra) - Uses, Dose, Side effects, MOA, Brands

Duvelisib is a medication that belongs to a class of drugs known as phosphoinositide 3-kinase (PI3K) inhibitors. It is used in the treatment of certain blood cancers, specifically chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) in adults.

Duvelisib works by blocking the activity of specific enzymes called PI3Ks that are involved in the growth and survival of cancer cells. By inhibiting these enzymes, duvelisib can help slow down or stop the growth of cancer cells in individuals with CLL or SLL.

Duvelisib (Copiktra) inhibits phosphatidylinositol 3-kinase (PI3K). It is available as oral capsules and is indicated for the treatment of refractory CLL, SLL, and Follicular lymphoma.

Duvelisib (Copiktra) Uses:

Chronic lymphocytic leukemia/small lymphocytic lymphoma relapsed or refractory:
- Duvelisib is used in the management of relapsed or recurrent chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in adult patients after 2 prior therapies.
Follicular lymphoma, relapsed or refractory:
- It can also be used in the treatment of relapsed or refractory follicular lymphoma (FL) in adult patients after at least 2 prior systemic therapies.

Read: Fludarabine (Fludara), Venetoclax (Venclexta), Chlorambucil, Obinutuzumab (Gazyva), Ofatumumab (Arzerra), and Fostamatinib (Tavalisse)

Duvelisib (Copiktra) Dose in Adults

Note:

You should also take medicine to prevent a type of lung infection called PCP.
Keep taking this PCP prevention medicine even after stopping duvelisib, until a certain type of white blood cell count (CD4+) goes above 200.
Also, consider taking medicine to prevent a virus called CMV from causing an infection or coming back.

Duvelisib (Copiktra) Dose in the treatment of relapsed or refractory Chronic lymphocytic leukemia and small lymphocytic lymphoma:

Duvelisib is typically taken orally at a dose of 25 mg.
It's taken twice a day for treating relapsed or refractory CLL/SLL.

Duvelisib (Copiktra) Dose in the treatment of relapsed or refractory Follicular lymphoma:

For Follicular Lymphoma (relapsed or refractory):

Take duvelisib orally at a dose of 25 mg.
Take it twice a day.

If you're also taking strong CYP3A4 inhibitors (like ketoconazole):

Reduce the duvelisib dose to 15 mg, taken twice daily.

If you miss a dose of duvelisib:

If it's less than 6 hours since the missed dose, take it right away, and then continue with the next dose as scheduled.
If it's more than 6 hours since the missed dose, skip the missed dose and just take the next dose at the usual time.

Duvelisib Dose in children:

Not indicated.

Pregnancy Risk Category: N

Duvelisib might harm an unborn baby based on how the drug works and what's been seen in animal tests.
Before starting the drug, it's crucial to know if a woman is pregnant.
If a woman can become pregnant, or if a man's partner can become pregnant, they should use reliable birth control during treatment and for one month after the last duvelisib dose.
There's also evidence from animal studies suggesting duvelisib might affect a man's ability to have children.

Use Duvelisib while you breastfeed

We don't know if duvelisib gets into breast milk.
But, because of the risk to a baby who is breastfeeding, the company that makes the drug advises against breastfeeding while on the medication and for one month after the last dose.

Duvelisib (Copiktra) Dose in Kidney disease:

For kidney function levels (CrCl) between 23 to 80 mL/minute:
- The manufacturer doesn't give any special dosing instructions because this level of kidney function doesn't seem to change how the body handles duvelisib in any important way.

For kidney function levels (CrCl) below 23 mL/minute:
- The manufacturer doesn't provide special dosing instructions either.

Duvelisib (Copiktra) Dose in Liver disease:

Before starting treatment (if there's liver impairment):

For all levels of liver impairment (Child Pugh class A, B, or C): The manufacturer doesn’t give any special dosing instructions because liver problems don’t seem to change how the body handles duvelisib in a way that's concerning.

If liver problems occur during treatment (judged by ALT and AST blood tests):

If the liver tests are a little high (3 to 5 times normal levels): Keep taking the same amount of duvelisib and get weekly checks until liver tests are closer to normal.
If the liver tests are more elevated (>5 to 20 times normal): Stop duvelisib for a while and get weekly checks. Once the liver tests are closer to normal, you can start duvelisib again. If it's the first time this happens, go back to the original dose. If it happens again, take a lower dose.
If the liver tests are very high (more than 20 times normal): Stop taking duvelisib completely.

Side effects:

Common Side Effects of Duvelisib (Copiktra):

Cardiovascular:
- Edema
Central Nervous System:
- Fatigue
- Headache
Dermatologic:
- Skin Rash
Endocrine & Metabolic:
- Hypophosphatemia
- Hyponatremia
- Hyperkalemia
- Hypoalbuminemia
- Hypocalcemia
- Hypokalemia
- Weight Loss
Gastrointestinal:
- Colitis
- Diarrhea
- Increased Serum Lipase
- Increased Serum Amylase
- Nausea
- Abdominal Pain
- Constipation
- Vomiting
- Mucositis
- Decreased Appetite
Hematologic & Oncologic:
- Neutropenia
- Anemia
- Thrombocytopenia
- Lymphocytosis
- Leukopenia
- Lymphocytopenia
Hepatic:
- Increased Serum Alanine Aminotransferase
- Increased Serum Aspartate Aminotransferase
- Decreased Serum Alkaline Phosphatase
- Increased Serum Alkaline Phosphatase
- Increased Serum Transaminases
Infection:
- Sepsis
- Serious Infection
Neuromuscular & Skeletal:
- Musculoskeletal Pain
Renal:
- Renal Insufficiency
- Increased Serum Creatinine
Respiratory:
- Upper Respiratory Tract Infection
- Pneumonia
- Cough
- Lower Respiratory Tract Infection
- Dyspnea
Miscellaneous:
- Fever

Less Common Side Effects Of Duvelisib (Copiktra):

Dermatologic:
- Dermatological Reaction
Infection:
- Cytomegalovirus Disease
Neuromuscular & Skeletal:
- Arthralgia
Respiratory:
- Pneumonitis
- Pneumonia Due To Pneumocystis Jiroveci

Contraindications to Duvelisib (Copiktra):

The manufacturer doesn't list any specific situations where you shouldn't take duvelisib.

Warnings and precautions

Suppression of bone marrow

Duvelisib can affect your bone marrow and reduce the number of certain blood cells, like neutrophils, platelets, and red blood cells.
Severe neutropenia (very low neutrophil count) usually starts within a few months of starting treatment.
To keep an eye on this, your doctor will check your neutrophil count regularly.
If your neutrophil count drops severely (grade 4), they will pause your duvelisib treatment and keep monitoring it until it's safer to resume. Depending on whether it's the first time or not, they may restart at the same dose or a lower one.

Dermatologic toxicities: [US Boxed Warning]

In some patients taking duvelisib, serious skin reactions have occurred, and these reactions can sometimes be fatal (very rare, but important to know).
These reactions include things like Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) and Toxic Epidermal Necrolysis (TEN).
These skin problems can start happening within a few days to several months after starting duvelisib.
The skin issues can vary, but often they cause itching, redness, or a rash, and in some cases, the skin may peel off.
If you notice any new or worsening skin problems, you should tell your doctor right away.
They'll check if any other medications you're taking could be causing the problem and might stop those.
Depending on how serious your skin reaction is, they might:
- For mild or moderate reactions (grade 1 or 2): You can usually keep taking duvelisib, and they'll give you some treatments like creams, antihistamines for itching, or corticosteroids to help with the skin issue.
- For severe reactions (grade 3): They'll stop duvelisib, give you corticosteroids or antihistamines, and closely watch you until the skin issue gets better. Once it's better, you can restart duvelisib but at a lower dose.
- If the skin reaction is very serious, doesn't improve, gets worse, or happens again, or if you have any form of Stevens-Johnson syndrome (SJS), TEN, or DRESS, they'll stop duvelisib for good.

Gastrointestinal toxicities: [US Boxed Warning]

Some people taking duvelisib can get serious stomach problems like severe diarrhea or inflammation of the gut (colitis). This happens to about 18% of people taking the drug, and it can sometimes be fatal.
If you're taking duvelisib, your doctor will keep an eye on you for these issues.
Most of these stomach problems start within the first 8 months of starting duvelisib but can begin as early as one day or as late as 33 months after starting. They usually last for about half a month but can be shorter or longer.
If you notice any new or worsening diarrhea, tell your doctor right away.
Depending on how bad it is, they might:
- Give you medications to help control the diarrhea or the inflammation in your gut.
- Stop the duvelisib temporarily or adjust the dose.
- Have you come in more often for check-ups.
- Sometimes, they might want to do more tests, like a colonoscopy, to see what's causing the problem.
- In serious cases, they might stop the duvelisib treatment completely.

Hepatotoxicity

Some people taking duvelisib have experienced elevated liver enzymes, which can be a sign of liver damage.
In some cases, multiple markers of liver health (like ALT, AST, and bilirubin) have shown high levels.
Most of these liver issues start within the first 2 months of taking the medication, but they can start as soon as a few days or as late as 26 months after beginning. These liver issues usually last about a month, but it can be shorter or longer.
While you're on duvelisib, your doctor will check your liver function to make sure it's working alright.
If your liver tests show problems:
- You might need more frequent check-ups.
- Your doctor might pause or adjust the dose of duvelisib.
- In serious situations, you might need to stop taking duvelisib completely.

Infection: [US Boxed Warning]

Some people taking duvelisib can get serious or even deadly infections. It's essential to watch out for any signs or symptoms of an infection.
If you think you might have an infection while on duvelisib, it might be best to stop the medicine until things are clear.
Common serious infections while on this drug are pneumonia, sepsis, and other respiratory infections.
Most infections appear within the first 6 months of starting the drug.
If you have an existing infection, treat it first before starting duvelisib.
If you get a severe infection while on duvelisib, you might need to stop the drug until the infection is gone. After that, you can resume duvelisib, possibly at a lower dose.
A specific kind of pneumonia, called Pneumocystis jirovecii pneumonia (PCP), has been reported in some patients on duvelisib. To avoid this:
- Take preventive medication (prophylaxis) while on duvelisib.
- Continue this preventive medication until a specific type of white blood cell count is above a certain level after stopping duvelisib.
- If you suspect PCP while on duvelisib, stop the drug. If PCP is confirmed, don't take duvelisib again.
There's also a risk of CMV (a virus) reactivation or infection with duvelisib. To manage this:
- Consider taking antiviral medicines to prevent CMV problems.
- If you have active CMV issues while on duvelisib, stop the drug until it's resolved.
- After that, if you start duvelisib again, you might take it at the same or a lower dose. Also, get monthly checks for CMV reactivation.

Pulmonary toxicities: [US Boxed Warning]

Some people taking duvelisib can develop serious lung issues called pneumonitis, and it can be fatal. This happens to about 5% of patients.
Most people notice these lung issues within the first 9 months of starting duvelisib, but it can start as early as 9 days or as late as 27 months after the start.
The typical duration of these lung problems is about a month, with most resolving in 2 months.
If you experience new or worsening lung symptoms like coughing, shortness of breath, low oxygen levels, or if X-rays show lung issues, it's crucial to stop the duvelisib and get it checked out.
If the lung problem turns out to be an infection, you can restart duvelisib after the infection and symptoms clear up.
If the lung issue is non-infectious and moderate (grade 2), you'll be given medications like corticosteroids to help. Once it's resolved, you can restart duvelisib, but at a lower dose.
If the non-infectious lung issue is severe, returns, or doesn't respond to the corticosteroids, you'll have to stop duvelisib.
If it's a serious or life-threatening issue, you'll also be given corticosteroids to manage the problem.

Duvelisib: Drug Interaction

Note: Drug Interaction Categories:

Risk Factor C: Monitor When Using Combination
Risk Factor D: Consider Treatment Modification
Risk Factor X: Avoid Concomitant Use

Risk Factor C (Monitor therapy)
Abemaciclib	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Abemaciclib.
AmLODIPine	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of AmLODIPine.
Apixaban	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Apixaban.
ARIPiprazole	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations.
Benzhydrocodone	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Benzhydrocodone. Specifically, the concentration of hydrocodone may be increased.
Blonanserin	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Blonanserin.
Bosentan	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Bosentan	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosentan. Management: Concomitant use of both a CYP2C9 inhibitor and a CYP3A inhibitor or a single agent that inhibits both enzymes with bosentan is likely to cause a large increase in serum concentrations of bosentan and is not recommended. See monograph for details.
Brexpiprazole	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Brexpiprazole. Management: The brexpiprazole dose should be reduced to 25% of usual if used together with both a moderate CYP3A4 inhibitor and a strong or moderate CYP2D6 inhibitor, or if a moderate CYP3A4 inhibitor is used in a CYP2D6 poor metabolizer.
Cannabidiol	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cannabidiol.
Cannabis	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased.
Chloramphenicol (Ophthalmic)	May enhance the adverse/toxic effect of Myelosuppressive Agents.
Clofazimine	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
CloZAPine	Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased.
Coccidioides immitis Skin Test	Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test.
Codeine	CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Codeine.
CYP3A4 Inducers (Moderate)	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
CYP3A4 Inhibitors (Moderate)	May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors).
CYP3A4 Substrates (High risk with Inhibitors)	Duvelisib may increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Deferasirox	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Denosumab	May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased.
Dofetilide	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dofetilide.
Dronabinol	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dronabinol.
Erdafitinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Erdafitinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Estrogen Derivatives	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Estrogen Derivatives.
Fosnetupitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Fosnetupitant	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Halofantrine. Management: Extreme caution, with possibly increased monitoring of ECGs, should be used if halofantrine is combined with moderate CYP3A4 inhibitors. Drugs listed as exceptions to this monograph are discussed in separate drug interaction monographs.
HYDROcodone	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of HYDROcodone.
Ifosfamide	CYP3A4 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide.
Imatinib	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Imatinib.
Larotrectinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Manidipine	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Manidipine.
Mirodenafil	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Mirodenafil.
Naldemedine	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naldemedine.
Nalfurafine	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Nalfurafine.
Netupitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
NiMODipine	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of NiMODipine.
Ocrelizumab	May enhance the immunosuppressive effect of Immunosuppressants.
OxyCODONE	CYP3A4 Inhibitors (Moderate) may enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased.
Palbociclib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Pidotimod	Immunosuppressants may diminish the therapeutic effect of Pidotimod.
Promazine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Propafenone	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Propafenone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Rupatadine	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Rupatadine.
Ruxolitinib	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ruxolitinib.
Salmeterol	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol.
Sarilumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
SAXagliptin	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of SAXagliptin.
Sildenafil	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sildenafil.
Silodosin	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Silodosin.
Siltuximab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Siponimod	Immunosuppressants may enhance the immunosuppressive effect of Siponimod.
Sipuleucel-T	Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T.
Tamsulosin	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tamsulosin.
Tertomotide	Immunosuppressants may diminish the therapeutic effect of Tertomotide.
Tetrahydrocannabinol	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol.
Ticagrelor	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ticagrelor.
Tocilizumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Trabectedin	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Trabectedin.
Trastuzumab	May enhance the neutropenic effect of Immunosuppressants.
Udenafil	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Udenafil.
Vilazodone	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vilazodone.
Vindesine	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vindesine.
Zuclopenthixol	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zuclopenthixol.
Risk Factor D (Consider therapy modification)
Acalabrutinib	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Acalabrutinib. Management: Reduce acalabrutinib dose to 100 mg once daily with concurrent use of a moderate CYP3A4 inhibitor. Monitor patient closely for both acalabrutinib response and evidence of adverse effects with any concurrent use.
Avanafil	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Avanafil. Management: The maximum avanafil adult dose is 50 mg per 24-hour period when used together with a moderate CYP3A4 inhibitor. Patients receiving such a combination should also be monitored more closely for evidence of adverse effects.
Baricitinib	Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted.
Brigatinib	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with moderate CYP3A4 inhibitors when possible. If such a combination cannot be avoided, reduce the dose of brigatinib by approximately 40% (ie, from 180 mg to 120 mg, from 120 mg to 90 mg, or from 90 mg to 60 mg).
Bromocriptine	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bromocriptine. Management: The bromocriptine dose should not exceed 1.6 mg daily with use of a moderate CYP3A4 inhibitor. The Cycloset brand specifically recommends this dose limitation, but other bromocriptine products do not make such specific recommendations.
Budesonide (Topical)	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Topical). Management: Per US prescribing information, avoid this combination. Canadian product labeling does not recommend strict avoidance. If combined, monitor for excessive glucocorticoid effects as budesonide exposure may be increased.
Cilostazol	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cilostazol. Management: Consider reducing the cilostazol dose to 50 mg twice daily in adult patients who are also receiving moderate inhibitors of CYP3A4.
Colchicine	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Colchicine. Management: Reduce colchicine dose as directed when using with a moderate CYP3A4 inhibitor, and increase monitoring for colchicine-related toxicity. See full monograph for details. Use extra caution in patients with impaired renal and/or hepatic function.
CYP3A4 Inhibitors (Strong)	May increase the serum concentration of Duvelisib. Management: Reduce the dose of duvelisib to 15 mg twice a day when used together with a strong CYP3A4 inhibitor.
Dabrafenib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects).
Dapoxetine	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Dapoxetine. Management: The dose of dapoxetine should be limited to 30 mg per day when used together with a moderate inhibitor of CYP3A4.
Deflazacort	CYP3A4 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Deflazacort. Management: Administer one third of the recommended deflazacort dose when used together with a strong or moderate CYP3A4 inhibitor.
DOXOrubicin (Conventional)	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to moderate CYP3A4 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided.
Echinacea	May diminish the therapeutic effect of Immunosuppressants.
Eletriptan	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eletriptan. Management: The use of eletriptan within 72 hours of a moderate CYP3A4 inhibitor should be avoided.
Eliglustat	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eliglustat. Management: Use should be avoided under some circumstances. See full drug interaction monograph for details.
Encorafenib	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Encorafenib. Management: Avoid concomitant use of encorafenib and moderate CYP3A4 inhibitors whenever possible. If concomitant administration is unavoidable, decrease the encorafenib dose to one-half of the encorafenib dose used prior to initiation of the CYP3A4 inhibitor.
Eplerenone	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eplerenone. Management: When used concomitantly with moderate inhibitors of CYP3A4, eplerenone dosing recommendations vary by indication and international labeling. See full drug interaction monograph for details.
Everolimus	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for most indications. See full monograph or prescribing information for specific dose adjustment and monitoring recommendations.
FentaNYL	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of FentaNYL. Management: Monitor patients closely for several days following initiation of this combination, and adjust fentanyl dose as necessary.
Fingolimod	Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections).
GuanFACINE	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of GuanFACINE. Management: Reduce the guanfacine dose by 50% when initiating this combination.
Ibrutinib	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ibrutinib. Management: When treating B-cell malignancies, decrease ibrutinib to 280 mg daily when combined with moderate CYP3A4 inhibitors. When treating graft versus host disease, monitor patients closely and reduce the ibrutinib dose as needed based on adverse reactions.
Ivacaftor	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivacaftor. Management: Ivacaftor dose reductions are required; consult full monograph content for specific age- and weight-based recommendations. No dose adjustment is needed when using ivacaftor/lumacaftor with a moderate CYP3A4 inhibitor.
Ivosidenib	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivosidenib. Management: Avoid use of moderate CYP3A4 inhibitors with ivosidenib whenever possible. If combined, monitor for increased ivosidenib toxicities. Drugs listed as exceptions are discussed in further detail in separate drug interaction monographs.
Leflunomide	Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly.
Lorlatinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences.
Lurasidone	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurasidone. Management: Lurasidone US labeling recommends reducing lurasidone dose by half with a moderate CYP3A4 inhibitor. Some non-US labeling recommends initiating lurasidone at 20 mg/day and limiting dose to 40 mg/day; avoid concurrent use of grapefruit products.
MiFEPRIStone	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus.
Nivolumab	Immunosuppressants may diminish the therapeutic effect of Nivolumab.
Olaparib	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Olaparib. Management: Avoid use of moderate CYP3A4 inhibitors in patients being treated with olaparib, if possible. If such concurrent use cannot be avoided, the dose of olaparib should be reduced to 150 mg twice daily.
Pitolisant	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant.
Ranolazine	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ranolazine. Management: Limit the ranolazine adult dose to a maximum of 500 mg twice daily in patients concurrently receiving moderate CYP3A4 inhibitors (e.g., diltiazem, verapamil, erythromycin, etc.).
Roflumilast	May enhance the immunosuppressive effect of Immunosuppressants.
Sirolimus	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sirolimus. Management: Monitor for increased serum concentrations of sirolimus if combined with a moderate CYP3A4 inhibitor. Lower initial sirolimus doses or sirolimus dose reductions will likely be required.
Sonidegib	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Sonidegib. Management: Avoid concomitant use of sonidegib and moderate CYP3A4 inhibitors when possible. When concomitant use cannot be avoided, limit CYP3A4 inhibitor use to less than 14 days and monitor for sonidegib toxicity (particularly musculoskeletal adverse reactions).
St John's Wort	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling.
Stiripentol	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring.
Suvorexant	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Suvorexant. Management: The recommended dose of suvorexant is 5 mg daily in patients receiving a moderate CYP3A4 inhibitor. The dose can be increased to 10 mg daily (maximum dose) if necessary for efficacy.
Tezacaftor	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tezacaftor. Management: When combined with moderate CYP3A4 inhibitors, tezacaftor/ivacaftor (100 mg/150 mg) should be given in the morning, every other day. Ivacaftor (150 mg) alone should be given in the morning, every other day on alternate days from tezacaftor/ivacaftor.
Tofacitinib	Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants.
Tolvaptan	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolvaptan. Management: Jynarque dose requires adjustment when used with a moderate CYP3A4 inhibitor. See labeling or full interaction monograph for specific recommendations. Use of Samsca with moderate CYP3A4 ihibitors should generally be avoided.
Vaccines (Inactivated)	Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation.
Venetoclax	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring these combinations.
Zopiclone	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zopiclone. Management: The starting adult dose of zopiclone should not exceed 3.75 mg if combined with a moderate CYP3A4 inhibitor. Monitor patients for signs and symptoms of zopiclone toxicity if these agents are combined.
Risk Factor X (Avoid combination)
Aprepitant	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Aprepitant.
Asunaprevir	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Asunaprevir.
BCG (Intravesical)	Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical).
BCG (Intravesical)	Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical).
Bosutinib	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Bosutinib.
Budesonide (Systemic)	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Systemic).
Cladribine	May enhance the immunosuppressive effect of Immunosuppressants.
Cladribine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Cobimetinib	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Cobimetinib. Management: Avoid the concomitant use of cobimetinib and moderate CYP3A4 inhibitors. If concurrent short term (14 days or less) use cannot be avoided, reduce the cobimetinib dose to 20 mg daily.
Conivaptan	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
CYP3A4 Inducers (Strong)	May decrease the serum concentration of Duvelisib.
Deferiprone	Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone.
Dipyrone	May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased
Domperidone	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Domperidone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Flibanserin	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Flibanserin.
Fosaprepitant	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Fosaprepitant.
Fusidic Acid (Systemic)	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Idelalisib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Ivabradine	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivabradine.
Lomitapide	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lomitapide.
Naloxegol	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Naloxegol.
Natalizumab	Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased.
Neratinib	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Neratinib.
Pimecrolimus	May enhance the adverse/toxic effect of Immunosuppressants.
Pimozide	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pimozide.
Simeprevir	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir.
Tacrolimus (Topical)	May enhance the adverse/toxic effect of Immunosuppressants.
Ulipristal	CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ulipristal. Management: This is specific for when ulipristal is being used for signs/symptoms of uterine fibroids (Canadian indication). When ulipristal is used as an emergency contraceptive, patients receiving this combination should be monitored for ulipristal toxicity.
Vaccines (Live)	Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants.

Monitoring parameters:

Blood Tests:

Check Complete Blood Count (CBC) with differential:
- Every 2 weeks for the first 2 months.
- Weekly if severe neutropenia (low white blood cells) is present.

Liver Tests:

Check liver enzymes (ALT and AST) regularly during treatment.

Pregnancy:

Test females who can become pregnant to ensure they're not pregnant before starting treatment.

Infections:

Look out for signs/symptoms of general infections.
Check specifically for CMV (a type of virus) using PCR or antigen tests.
- If CMV appears while on duvelisib, monitor monthly for CMV reactivation once the drug is restarted.
Watch for PCP (a type of pneumonia).

Skin Issues:

Monitor for signs of skin problems.

Stomach Issues:

Look out for gastrointestinal problems like colitis and diarrhea.

Lung Issues:

Watch for lung symptoms and changes on X-rays.

Medication Adherence:

Make sure the patient is taking the medication as prescribed.

How to administer Duvelisib (Copiktra)?

Taking the Medication:

You can take the capsules with or without food.
Swallow the capsules whole. Don't open, break, or chew them.

Infection Precautions:

Take preventive medication for PCP (a type of pneumonia) while on the treatment and keep taking it until a specific white blood cell count (CD4+ T cell) is above 200.
Consider taking antiviral medications to prevent CMV (a type of virus) from starting or coming back while on the treatment.

Mechanism of action of Duvelisib (Copiktra):

Duvelisib is a medication that you take by mouth.
It's a type of drug that works by blocking certain proteins in the body called PI3K-δ and PI3K-γ.
These proteins are often found in blood cancer cells.
Duvelisib stops these proteins from working, which slows down or stops the growth of cancer cells.
Importantly, it affects cancer cells more than normal cells, so normal cells can survive.
Duvelisib also does other things, like stopping certain signals in cancer cells and preventing them from moving around and spreading.
It can be effective in treating certain types of blood cancers, like CLL, by reducing the growth of cancer cells and limiting their ability to move and cause problems.

Distribution:

Once in the body, it spreads out and occupies a space roughly equal to 28.5 liters (like filling a big container).

Protein binding:

Over 98% of the drug sticks to proteins in the blood, meaning only a tiny amount is "free" and active.

How it's processed (Metabolism):

The liver breaks it down, mainly using an enzyme called CYP3A4.

Absorption (Bioavailability):

When you take it, only 42% of the drug actually gets into the bloodstream and becomes available to act in the body.

How long it lasts (Half-life):

Half of the drug is removed from the body in about 4.7 hours.

When it's most active (Time to peak):

The highest amount of drug in the blood is seen about 1 to 2 hours after taking it.

How it leaves the body (Excretion):

It mainly goes out with feces (79%), and only 11% of that is the unchanged drug.
A smaller amount (14%) is removed in urine, and less than 1% of that is the unchanged drug.

International Brand Names of Duvelisib: