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PI3K inhibitors

Medically reviewed by Carmen Pope, BPharm. Last updated on April 12, 2023.

Other names: phosphoinositide 3-kinase inhibitors

What are PI3K inhibitors?

Phosphoinositide 3-kinase (PI3K) inhibitors are a class of medicines that have been developed to inhibit one or more of the phosphoinositide 3-kinase enzymes. These enzymes form part of the PI3K/AKT/mTOR pathway, which is a pathway involved in cell growth and survival, as well as several other processes that are frequently activated in many cancers.

By inhibiting these enzymes, PI3K inhibitors cause cell death, inhibit the proliferation of malignant cells, and interfere with several signaling pathways.

What are PI3K inhibitors used for?

PI3K inhibitors are usually given to treat certain cancers that have relapsed or are unresponsive to other cancer treatments. Typically, at least two other cancer treatments need to have been tried and been unsuccessful or not tolerated before PI3K inhibitors are given. The following PI3K inhibitors may be given alone or in combination with other medications in the treatment of:

What are the differences between PI3K inhibitors?

Different PI3K inhibitors inhibit different PI3K enzymes, and this contributes to differences in their effectiveness against certain types of cancers and their side effects.

Alpelisib is a selective inhibitor of the α isoform of phosphatidylinositol-3-kinase (PI3Kα). 40% of HR+HER2- breast cancers have a mutation in the gene that encodes PI3Kα and mutations in PIK3CA are also associated with overgrowths and malformations that cause PROS.

Copanlisib is more likely than other PI3K inhibitors to increase blood pressure and is usually administered via a one hour IV infusion on days 1,8, and 15 of a 28-day treatment cycle.

Duvelisib is given orally twice a day and common severe side effects include neutropenia (30%), diarrhea (15%), anemia (13%), and colitis (12%).

Idelalisib was the first PI3K inhibitor to be approved by the FDA and is usually taken orally twice daily. In addition to other serious side effects, it has a higher rate of severe or potentially fatal liver toxicity.

Leniolisib is an oral, selective, phosphoinositide 3-kinase-delta inhibitor (PI3Kδ) inhibitor that treats APDS by inhibiting the production of phosphatidylinositol-3-4-5-trisphosphate, a cellular messenger that is involved in many cell functions.

Generic name Brand name examples
alpelisib Piqray, Vijoice
copanlisib Aliqopa
duvelisib Copiktra
idelalisib Zydelig
leniolisib Joenja

Are PI3K inhibitors safe?

Severe and potentially life-threatening reactions have been reported with PI3K inhibitors.

Rashes and skin reactions: Several grade 3 (severe, covering more than 30% body surface area or with evidence of infection) skin reactions, including exfoliative dermatitis and toxic epidermal necrolysis, have been reported with alpelisib, idelalisib, and other PI3K inhibitors. A dermatologist should be consulted and PI3K inhibitors withheld if any skin reaction occurs.

Infections: An increase in the number of infections, and infections associated with unusual organisms, such as Pneumocystis jirovecii and cytomegalovirus (CMV) have been reported associated with PI3K inhibitor use. It is now recommended that P. jirovecii pneumonia (PJP) prophylaxis with trimethoprim/sulfamethoxazole be provided for all patients receiving PI3K inhibitor treatment. CMV status should be assessed monthly and antiviral treatment initiated and PI3K inhibitor therapy withheld if CMV levels are increasing, or discontinued if there is evidence of end-organ damage such as colitis, hepatitis, or retinitis.

High blood pressure (hypertension): Higher rates of severe hypertension have been reported with copanlisib compared with other PI3K inhibitors. Copanlisib may need to be withheld, the dosage reduced or discontinued if blood pressure recordings exceed 150/90 mm Hg.

Hyperglycemia (high blood glucose levels): Has been reported in 65% of patients receiving alpelisib for breast cancer; severe hyperglycemia (grade 3 or 4) was reported in 3.9% of patients in clinical trials.

Severe, potentially life-threatening diarrhea has been reported with several PI3K inhibitors. This may lead to a hole or tear (perforation) in the intestines. Seek urgent medical advice.

Pneumonitis has also been associated with PI3K inhibitors. Report any unusual respiratory symptoms to your doctor.

Bone marrow suppression, including grade 3 or 4 events, has also been reported, sometimes in up to a quarter of people receiving PI3K agents. Blood counts should be monitored weekly or two weekly during treatment, and treatment may need to be withheld, the dosage reduced or discontinued depending on the severity and persistence of the neutropenia.

Severe or fatal liver damage has been reported in 16-18% of patients receiving idelalisib, and elevations in liver enzymes have been reported with other PI3K inhibitors. Liver function should be monitored before and during therapy.

Leniolisib can be toxic to a developing baby and females of reproductive potential should use highly effective contraception.

For a complete list of severe side effects, please refer to the individual drug monographs.

What are the side effects of PI3K inhibitors?

Side effects differ depending on the PI3K inhibitor being taken but may include:

For a complete list of side effects, please refer to the individual drug monographs.

List of PI3K inhibitors

View by  Brand | Generic
Drug Name Avg. Rating Reviews
Zydelig (Pro)
Generic name: idelalisib
2 reviews
Piqray (Pro)
Generic name: alpelisib
2 reviews
Vijoice (Pro)
Generic name: alpelisib
No reviews
Joenja (Pro)
Generic name: leniolisib
No reviews
Copiktra (Pro)
Generic name: duvelisib
No reviews
Generic name: copanlisib
No reviews
For ratings, users were asked how effective they found the medicine while considering positive/adverse effects and ease of use (1 = not effective, 10 = most effective).

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.