Gavreto Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Gavreto?

Gavreto (pralsetinib) is a kinase inhibitor used to treat adult patients with metastatic rearranged during transfection (RET), fusion-positive, non-small cell lung cancer (NSCLC) as detected by an FDA approved test.

What Are Side Effects of Gavreto?

Side effects of Gavreto include:

fatigue,
constipation,
musculoskeletal pain,
high blood pressure (hypertension),
fever,
fluid retention (edema),
diarrhea,
dry mouth,
cough,
pneumonia,
decreased lymphocytes,
decreased neutrophils,
decreased phosphate,
decreased hemoglobin,
decreased sodium,
decreased calcium, and
increased alanine aminotransferase (alt)

Dosage for Gavreto

The recommended dosage of Gavreto in adults is 400 mg orally once daily on an empty stomach (no food intake for at least 2 hours before and at least 1 hour after taking Gavreto).

Gavreto In Children

The safety and effectiveness of Gavreto have not been established in pediatric patients.

What Drugs, Substances, or Supplements Interact with Gavreto?

Gavreto may interact with other medicines such as:

strong CYP3A inhibitors,
combined P-gp and strong CYP3A inhibitors, and
strong CYP3A inducers

Tell your doctor all medications and supplements you use.

Gavreto During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Gavreto; it may harm a fetus. The pregnancy status of females of reproductive potential should be verified prior to initiating Gavreto. Females of reproductive potential are advised to use effective non-hormonal contraception during treatment with Gavreto and for 2 weeks after the final dose. Gavreto may render hormonal contraceptives ineffective. Males with female partners of reproductive potential are advised to use effective contraception during treatment with Gavreto and for 1 week after the final dose. It is unknown if Gavreto passes into breast milk. Because of the potential for serious adverse reactions in breastfed children, breastfeeding is not advised during treatment with Gavreto and for 1 week after the final dose.

Additional Information

Our Gavreto (pralsetinib) Capsules, for Oral Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

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.

QUESTION

Lung cancer is a disease in which lung cells grow abnormally in an uncontrolled way. See Answer

Gavreto Consumer Information

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:

fever, chills;
new or worsening cough, shortness of breath, or chest pain;
severe headache, dizziness, confusion, trouble speaking;
any wound that will not heal;
unusual bleeding--bruising, nosebleeds, bleeding gums, abnormal vaginal bleeding, any bleeding that will not stop;
signs of bleeding inside your body--weakness, drowsiness, pink or brown urine, bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds;
low blood cell counts--fever, tiredness, sore throat, mouth sores, skin sores, pale skin, cold hands and feet, feeling light-headed or short of breath; or
liver problems--nausea, vomiting, loss of appetite, stomach pain (upper right side), tiredness, dark urine, jaundice (yellowing of the skin or eyes).

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

Common side effects may include:

high blood pressure;
low blood cell counts or other abnormal laboratory tests;
muscle or joint pain;
feeling tired; or
constipation.

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.

Read the entire detailed patient monograph for Gavreto (Pralsetinib Capsules)

Learn More »

SLIDESHOW

Lung Cancer: Early Signs, Symptoms, Stages See Slideshow

Gavreto Professional Information

SIDE EFFECTS

The following clinically significant adverse reactions are described elsewhere in the labeling:

Interstitial Lung Disease/Pneumonitis [see WARNINGS AND PRECAUTIONS]
Hypertension [see WARNINGS AND PRECAUTIONS]
Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
Hemorrhagic Events [see WARNINGS AND PRECAUTIONS]
Tumor Lysis Syndrome [see WARNINGS AND PRECAUTIONS]
Risk of Impaired Wound Healing [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The pooled safety population in the WARNINGS AND PRECAUTIONS reflect exposure to GAVRETO as a single agent at 400 mg orally once daily in 438 patients with RET-altered solid tumors, including with RET fusion-positive NSCLC (n = 220), and RET-altered thyroid cancer (n=138), in ARROW [see Clinical Studies]. Among 438 patients who received GAVRETO, 47% were exposed for 6 months or longer and 23% were exposed for greater than one year.

The most common adverse reactions (≥ 25%) were constipation, hypertension, fatigue, musculoskeletal pain and diarrhea. The most common Grade 3-4 laboratory abnormalities (≥ 2%) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased phosphate, decreased calcium (corrected), decreased sodium, increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), decreased platelets, and increased alkaline phosphatase.

RET Fusion-Positive Non-Small Cell Lung Cancer

The safety of GAVRETO was evaluated as a single agent at 400 mg orally once daily in 220 patients with metastatic rearranged during transfection (RET fusion-positive) non-small cell lung cancer (NSCLC) in ARROW [see Clinical Studies]. Among the 220 patients who received GAVRETO, 42% were exposed for 6 months or longer and 19% were exposed for greater than one year.

The median age was 60 years (range: 26 to 87 years); 52% were female, 50% were White, 41% were Asian, and 4% were Hispanic/Latino.

Serious adverse reactions occurred in 45% of patients who received GAVRETO. The most frequent serious adverse reaction (in ≥ 2% of patients) was pneumonia, pneumonitis, sepsis, urinary tract infection, and pyrexia. Fatal adverse reactions occurred in 5% of patients; fatal adverse reactions which occurred in > 1 patient included pneumonia (n = 3) and sepsis (n = 2).

Permanent discontinuation due to an adverse reaction occurred in 15% of patients who received GAVRETO. Adverse reactions resulting in permanent discontinuation which occurred in > 1 patient included pneumonitis (1.8%), pneumonia (1.8%), and sepsis (1%).

Dosage interruptions due to an adverse reaction occurred in 60% of patients who received GAVRETO. Adverse reactions requiring dosage interruption in ≥ 2% of patients included neutropenia, pneumonitis, anemia, hypertension, pneumonia, pyrexia, increased aspartate aminotransferase (AST), increased blood creatine phosphokinase, fatigue, leukopenia, thrombocytopenia, vomiting, increased alanine aminotransferase (ALT), sepsis, and dyspnea.

Dose reductions due to adverse reactions occurred in 36% of patients who received GAVRETO. Adverse reactions requiring dosage reductions in ≥ 2% of patients included neutropenia, anemia, pneumonitis, neutrophil count decreased, fatigue, hypertension, pneumonia, and leukopenia.

Table 4 summarizes the adverse reactions in RET Fusion-Positive NSCLC Patients in ARROW.

Table 4: Adverse Reactions (≥ 15%) in RET Fusion-Positive NSCLC Patients Who Received GAVRETO in ARROW

Adverse Reactions	GAVRETO N=220
Adverse Reactions	Grades 1-4 (%)	Grades 3-4 (%)
General
Fatigue¹	35	2.3*
Pyrexia	20	0
Edema²	20	0
Gastrointestinal
Constipation	35	1*
Diarrhea³	24	3.2*
Dry Mouth	16	0
Musculoskeletal Disorders
Musculoskeletal Pain⁴	32	0
Vascular
Hypertension⁵	28	14*
Respiratory, thoracic and mediastinal
Cough⁶	23	0.5*
Infections
Pneumonia⁷	17	8
¹ Fatigue includes fatigue, asthenia ² Edema includes edema peripheral, face edema, periorbital edema, eyelid edema, edema generalized, swelling ³ Diarrhea includes diarrhea, colitis, enteritis ⁴ Musculoskeletal pain includes back pain, myalgia, arthralgia, pain in extremity, musculoskeletal pain, neck pain, musculoskeletal chest pain, bone pain, musculoskeletal stiffness, arthritis, spinal pain ⁵ Hypertension includes hypertension, blood pressure increased ⁶ Cough includes cough, productive cough, upper-airway cough syndrome ⁷ Pneumonia includes pneumonia, atypical pneumonia, lung infection, pneumocystis jirovecii pneumonia, pneumonia bacterial, pneumonia cytomegaloviral, pneumonia haemophilus, pneumonia influenza, pneumonia streptococcal *Only includes a Grade 3 adverse reaction

Table 5 summarizes the laboratory abnormalities in ARROW.

Table 5: Select Laboratory Abnormalities (≥ 20%) Worsening from Baseline in RET Fusion-Positive NSCLC Patients Who Received GAVRETO in ARROW

Laboratory Abnormality	GAVRETO N=220
Laboratory Abnormality	Grades 1-4 (%)	Grades 3-4 (%)
Chemistry
Increased AST	74	2.3
Increased ALT	49	2.3
Increased alkaline phosphatase	42	1.8
Decreased calcium (corrected)	39	1.8
Decreased albumin	36	0
Decreased phosphate	35	11
Increased creatinine	33	0.5
Decreased sodium	29	7
Increased potassium	26	0.9
Hematology
Decreased neutrophils	61	16
Decreased hemoglobin	58	9
Decreased lymphocytes	56	19
Decreased platelets	27	3.2
Denominator for each laboratory parameter is based on the number of patients with a baseline and post-treatment laboratory value available, which ranged from 216 to 218 patients.

Clinically relevant laboratory abnormalities < 20% of patients who received GAVRETO included increased phosphate (10%).

RET-altered Thyroid Cancer

The safety of GAVRETO was evaluated as a single agent at 400 mg orally once daily in 138 patients with RET-altered Thyroid Cancer in ARROW [see Clinical Studies]. Among the 138 patients who received GAVRETO, 68% were exposed for 6 months or longer, and 40% were exposed for greater than one year.

The median age was 59 years (range: 18 to 83 years); 36% were female, 74% were White, 17% were Asian, and 6% were Hispanic/Latino.

Serious adverse reactions occurred in 39% of patients who received GAVRETO. The most frequent serious adverse reactions (in ≥ 2% of patients) were pneumonia, pneumonitis, urinary tract infection, pyrexia, fatigue, diarrhea, dizziness, anemia, hyponatremia, and ascites. Fatal adverse reaction occurred in 2.2% of patients; fatal adverse reactions that occurred in > 1 patient included pneumonia (n=2).

Permanent discontinuation due to an adverse reaction occurred in 9% of patients who received GAVRETO. Adverse reactions resulting in permanent discontinuation which occurred in > 1 patient included fatigue, pneumonia and anemia.

Dosage interruptions due to an adverse reaction occurred in 67% of patients who received GAVRETO. Adverse reactions requiring dosage interruption in ≥ 2% of patients included neutropenia, hypertension, diarrhea, fatigue, pneumonitis, anemia, increased blood creatine phosphokinase, pneumonia, urinary tract infection, musculoskeletal pain, vomiting, pyrexia, increased AST, dyspnea, hypocalcemia, cough, thrombocytopenia, abdominal pain, increased blood creatinine, dizziness, headache, decreased lymphocyte count, stomatitis, and syncope.

Dose reductions due to adverse reactions occurred in 44% of patients who received GAVRETO. Adverse reactions requiring dosage reductions in ≥ 2% of patients included neutropenia, anemia, hypertension, increased blood creatine phosphokinase, decreased lymphocyte count, pneumonitis, fatigue and thrombocytopenia.

Table 6 summarizes the adverse reactions occurring in RET-altered Thyroid Cancer Patients in ARROW.

Table 6: Adverse Reactions (≥ 15%) in RET-altered Thyroid Cancer Patients Who Received GAVRETO in ARROW

Adverse Reactions	GAVRETO N =138
Adverse Reactions	Grades 1-4 (%)	Grades 3-4 (%)
Musculoskeletal
Musculoskeletal Pain¹	42	0.7*
Gastrointestinal
Constipation	41	0.7*
Diarrhea²	34	5*
Abdominal Pain³	17	0.7*
Dry mouth	17	0
Stomatitis⁴	17	0.7*
Nausea	17	0.7*
Vascular
Hypertension	40	21*
General
Fatigue⁵	38	6*
Edema⁶	29	0
Pyrexia	22	2.2*
Nervous System
Headache⁷	24	0
Peripheral Neuropathy⁸	20	0
Dizziness⁹	19	0.7*
Dysgeusia¹⁰	17	0
Respiratory
Cough¹¹	27	1.4*
Dyspnea¹²	22	2.2*
Skin and Subcutaneous
Rash¹³	24	0
Metabolism and Nutrition
Decreased Appetite	15	0
¹ Musculoskeletal Pain includes arthralgia, arthritis, back pain, bone pain, musculoskeletal chest pain, musculoskeletal pain, musculoskeletal stiffness, myalgia, neck pain, non-cardiac chest pain, pain in extremity, spinal pain ² Diarrhea includes colitis, diarrhea ³ Abdominal Pain includes abdominal discomfort, abdominal pain, abdominal pain upper, abdominal tenderness, epigastric discomfort ⁴ Stomatitis includes mucosal inflammation, stomatitis, tongue ulceration ⁵ Fatigue includes asthenia, fatigue ⁶ Edema includes eyelid edema, face edema, edema, edema peripheral, periorbital edema ⁷ Headache includes headache, migraine ⁸ Peripheral neuropathy includes dysaesthesia, hyperaesthesia, hypoaesthesia, neuralgia, neuropathy peripheral, paraesthesia, peripheral sensory neuropathy, polyneuropathy ⁹ Dizziness includes dizziness, dizziness postural, vertigo ¹⁰ Dysgeusia includes ageusia, dysgeusia ¹¹ Cough includes cough, productive cough, upper-airway cough syndrome ¹² Dyspnea includes dyspnea, dyspnea exertional ¹³ Rash includes dermatitis, dermatitis acneiform, eczema, palmar-plantar, erythrodysaesthesia syndrome, rash, rash erythematous, rash macular, rash maculo-papular, rash papular, rash pustular * Only includes a Grade 3 adverse reaction

Clinically relevant adverse reactions in < 15% of patients who received GAVRETO included tumor lysis syndrome and increased creatine phosphokinase.

Table 7 summarizes the laboratory abnormalities occurring in RET-altered Thyroid Cancer Patients in ARROW.

Table 7: Select Laboratory Abnormalities (≥ 20%) Worsening from Baseline in RET-altered Thyroid Cancer Patients Who Received GAVRETO in ARROW

Laboratory Abnormality	GAVRETO N=138
Laboratory Abnormality	Grades 1-4 (%)	Grades 3-4 (%)
Chemistry
Decreased calcium (corrected)	70	9
Increased AST	69	4.3
Increased ALT	43	3.6
Increased creatinine	41	0
Decreased albumin	41	1.5
Decreased sodium	28	2.2
Decreased phosphate	28	8
Decreased magnesium	27	0.7
Increased potassium	26	1.4
Increased bilirubin	24	1.4
Increased alkaline phosphatase	22	1.4
Hematology
Decreased lymphocytes	67	27
Decreased hemoglobin	63	13
Decreased neutrophils	59	16
Decreased platelets	31	2.9
Denominator for each laboratory parameter is based on the number of patients with a baseline and post-treatment laboratory value available, which ranged from 135 to 138 patients.

Clinically relevant laboratory abnormalities in patients who received GAVRETO included increased phosphate (40%).

DRUG INTERACTIONS

Effects Of Other Drugs On GAVRETO

Strong CYP3A Inhibitors

Avoid coadministration with strong CYP3A inhibitors. Coadministration of GAVRETO with a strong CYP3A inhibitor increases pralsetinib exposure, which may increase the incidence and severity of adverse reactions of GAVRETO.

Avoid coadministration of GAVRETO with combined P-gp and strong CYP3A inhibitors. If coadministration with a combined P-gp and strong CYP3A inhibitor cannot be avoided, reduce the GAVRETO dose [see DOSAGE AND ADMINISTRATION, CLINICAL PHARMACOLOGY].

Strong CYP3A Inducers

Coadministration of GAVRETO with a strong CYP3A inducer decreases pralsetinib exposure, which may decrease efficacy of GAVRETO. Avoid coadministration of GAVRETO with strong CYP3A inducers. If coadministration of GAVRETO with strong CYP3A inducers cannot be avoided, increase the GAVRETO dose [see DOSAGE AND ADMINISTRATION, CLINICAL PHARMACOLOGY].

Read the entire FDA prescribing information for Gavreto (Pralsetinib Capsules)