FRUZAQLA^® (fruquintinib) safety profile

Across multiple pivotal phase 3 clinical studies, FRUZAQLA demonstrated a manageable and predictable* safety profile.^1-4

In the FRESCO and FRESCO-2 clinical trials, adverse reactions with FRUZAQLA were generally manageable and predictable.^1-4

In pooled monotherapy studies, among the 911 patients who received FRUZAQLA, 23% were exposed for ≥6 months and 3.5% were exposed for ≥1 year. All patients received at least 1 dose of FRUZAQLA at the recommended 5 mg daily for the first 21 days of each 28-day cycle.¹

The most common adverse reactions (incidence ≥20%) included¹:

hypertension
palmar-plantar erythrodysesthesia (hand-foot skin reactions)
proteinuria
dysphonia
abdominal pain
diarrhea
asthenia

*Predictable refers to ARs consistent with inhibition of VEGF and VEGFR.
Despite predictability, individual patient experiences may vary.

In FRESCO, the majority of ARs were manageable and predictable^1-3

FRESCO was a single-country* study that evaluated fruquintinib safety and efficacy^1,2

ARs that occurred in ≥10% of patients¹

In the FRESCO clinical trial, adverse reactions occurring in ≥10% of patients included hypertension, proteinuria, palmar-plantar erythrodysesthesia, dysphonia, stomatitis, abdominal pain, hemorrhage, diarrhea, fatigue, musculoskeletal pain, anorexia, hypothyroidism, back pain, arthralgia, and throat pain. — *The FRESCO study was conducted in China.
^aRepresents a composite of multiple related terms.

Predictable is defined as ARs that are consistent with inhibition of VEGF and VEGFR^†1
Serious ARs occurred in 15% of patients treated with FRUZAQLA + BSC. Serious ARs in ≥2% of patients treated with FRUZAQLA + BSC included intestinal obstruction (2.9%) and hemorrhage (2.2%)¹
Fatal ARs occurred in 7 (2.5%) patients treated with FRUZAQLA + BSC, including cerebral infarction (n=1), gastrointestinal hemorrhage (n=1), hemoptysis (n=1), bacterial infection (n=1), lung/lower respiratory infection (n=2), and multiple organ dysfunction (n=1)¹

^†Despite predictability, individual patient experiences may vary.

FRUZAQLA demonstrated a low rate of myelosuppression similar to placebo⁵:

Hematologic abnormalities of grade 3/4 in >2% of patients:
- Anemia: 0.7% with FRUZAQLA + BSC vs 2.2% with placebo + BSC
- Decrease platelet count: 2.9% with FRUZAQLA + BSC vs 0% with placebo + BSC
Note: There were no reportable differences in neutrophil count for the FRUZAQLA + BSC or placebo + BSC treatment arms.

FRUZAQLA had low Grade 3/4 laboratory abnormalities¹

Select laboratory abnormalities worsening from baseline and occurring in ≥20% of patients^1,a,b

In the FRESCO clinical trial, select laboratory occurring in ≥20% of patients included an increase in creatinine, glucose, aspartate aminotransferase, alkaline phosphatase, bilirubin, and alanine aminotransferase and a decrease in sodium, platelets, urate, calcium, hemoglobin, and potassium.

^aGraded according to NCI CTCAE version 4.03.¹
^bEach test incidence is based on the number of patients who had both baseline and at least one on‑study laboratory measurement available: FRUZAQLA (range: 257-277) and placebo (range: 126-134).¹

Manageable safety profile with FRUZAQLA as demonstrated in the FRESCO trial^1,2

Adverse reactions were managed through dose modifications when appropriate^1,2:

Dose interruptions: 35.3% with FRUZAQLA + BSC vs 10.2% with placebo + BSC
Dose reductions: 24.1% with FRUZAQLA + BSC vs 4.4% with placebo + BSC

Fewer than 1 in 5 patients discontinued due to ARs^1,2:

15% with FRUZAQLA + BSC vs 6% for placebo + BSC

AR=adverse reaction; BSC=best supportive care; NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events; VEGF=Vascular endothelial growth factor; VEGFR=Vascular endothelial growth factor receptor.

Clinical results with FRUZAQLA

Learn about the efficacy results from the FRESCO and FRESCO-2 studies in patients with previously treated mCRC.

Explore efficacy data

Evolving patient unmet needs in mCRC

Learn how shifting demographics and daily activity considerations are shaping the treatment needs of patients with metastatic colorectal cancer.

Understand patient needs

FRUZAQLA patient profiles

Learn about patient types and why they may benefit from FRUZAQLA.

Review patient profiles

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hypertension occurred in 49% of 911 patients with mCRC treated with FRUZAQLA, including Grade 3-4 events in 19%, and hypertensive crisis in three patients (0.3%). Do not initiate FRUZAQLA unless blood pressure is adequately controlled. Monitor blood pressure weekly for the first month and at least monthly thereafter as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue FRUZAQLA based on severity of hypertension.

Hemorrhagic Events including serious, fatal events can occur with FRUZAQLA. In 911 patients with mCRC treated with FRUZAQLA, 6% of patients experienced gastrointestinal hemorrhage, including 1% with a Grade ≥3 event and 2 patients with fatal hemorrhages. Permanently discontinue FRUZAQLA in patients with severe or life-threatening hemorrhage. Monitor the International Normalized Ratio (INR) levels in patients receiving anticoagulants.

Infections. FRUZAQLA can increase the risk of infections, including fatal infections. In 911 patients with mCRC treated with FRUZAQLA, the most common infections were urinary tract infections (6.8%), upper respiratory tract infections (3.2%) and pneumonia (2.5%); fatal infections included pneumonia (0.4%), sepsis (0.2%), bacterial infection (0.1%), lower respiratory tract infection (0.1%), and septic shock (0.1%). Withhold FRUZAQLA for Grade 3 or 4 infections, or worsening infection of any grade. Resume FRUZAQLA at the same dose when the infection has resolved.

Gastrointestinal Perforation occurred in patients treated with FRUZAQLA. In 911 patients with mCRC treated with FRUZAQLA, 1.3% experienced a Grade ≥3 gastrointestinal perforation, including one fatal event. Permanently discontinue FRUZAQLA in patients who develop gastrointestinal perforation or fistula.

Hepatotoxicity. FRUZAQLA can cause liver injury. In 911 patients with mCRC treated with FRUZAQLA, 48% experienced increased ALT or AST, including Grade ≥3 events in 5%, and fatal events in 0.2% of patients. Monitor liver function tests (ALT, AST, and bilirubin) before initiation and periodically throughout treatment with FRUZAQLA. Temporarily hold and then reduce or permanently discontinue FRUZAQLA depending on the severity and persistence of hepatotoxicity as manifested by elevated liver function tests.

Proteinuria. FRUZAQLA can cause proteinuria. In 911 patients with mCRC treated with FRUZAQLA, 36% experienced proteinuria and 2.5% of patients experienced Grade ≥3 events. Monitor for proteinuria before initiation and periodically throughout treatment with FRUZAQLA. For proteinuria ≥2g/24 hours, withhold FRUZAQLA until improvement to ≤Grade 1 proteinuria and resume FRUZAQLA at a reduced dose. Discontinue FRUZAQLA in patients who develop nephrotic syndrome.

Palmar-Plantar Erythrodysesthesia (PPE) occurred in 35% of 911 patients treated with FRUZAQLA, including 8% with Grade 3 events. Based on severity of PPE, withhold FRUZAQLA and then resume at the same or reduced dose.

Posterior Reversible Encephalopathy Syndrome (PRES), a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, occurred in one of 911 patients treated with FRUZAQLA. Perform an evaluation for PRES in any patient presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue FRUZAQLA in patients who develop PRES.

Impaired Wound Healing. In 911 patients with mCRC treated with FRUZAQLA, 1 patient experienced a Grade 2 event of wound dehiscence. Do not administer FRUZAQLA for at least 2 weeks prior to major surgery. Do not administer FRUZAQLA for at least 2 weeks after major surgery and until adequate wound healing. The safety of resumption of FRUZAQLA after resolution of wound healing complications has not been established.

Arterial Thromboembolic Events. In 911 patients with mCRC treated with FRUZAQLA, 0.8% of patients experienced an arterial thromboembolic event. Initiation of FRUZAQLA in patients with a recent history of thromboembolic events should be carefully considered. In patients who develop arterial thromboembolism, discontinue FRUZAQLA.

Allergic Reactions to FD&C Yellow No. 5 (Tartrazine) and No. 6 (Sunset Yellow FCF). FRUZAQLA 1 mg capsules contain FD&C Yellow No. 5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. FRUZAQLA 1 mg contains FD&C Yellow No. 6 (sunset yellow FCF), which may cause allergic reactions.

Embryo-Fetal Toxicity. Based on findings in animal studies and its mechanism of action, FRUZAQLA can cause fetal harm when administered to pregnant women. Advise pregnant women of the potential risk to a fetus.

ADVERSE REACTIONS

The most common adverse reactions (incidence ≥20%) following treatment with FRUZAQLA included hypertension, palmar-plantar erythrodysesthesia (hand-foot skin reactions), proteinuria, dysphonia, abdominal pain, diarrhea, and asthenia.

DRUG INTERACTIONS

Avoid concomitant administration of FRUZAQLA with strong or moderate CYP3A inducers.

USE IN SPECIFIC POPULATIONS

Lactation: Advise women not to breastfeed during treatment with FRUZAQLA and for 2 weeks after the last dose.

Females and Males of Reproductive Potential

Pregnancy Testing: Verify pregnancy status of females of reproductive potential prior to initiating FRUZAQLA.
Contraception: Females of childbearing potential and males with female partners of childbearing potential should use effective contraception during treatment and for 2 weeks after the last dose of FRUZAQLA.
Infertility: Advise females of reproductive potential that FRUZAQLA may cause post-implantation loss.

To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals at 1-844-662-8532 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see FRUZAQLA (fruquintinib) full Prescribing Information.

FRUZAQLA^® (fruquintinib) safety profile

Across multiple pivotal phase 3 clinical studies, FRUZAQLA demonstrated a manageable and predictable* safety profile.^1-4

In FRESCO, the majority of ARs were manageable and predictable^1-3

FRESCO was a single-country* study that evaluated fruquintinib safety and efficacy^1,2

ARs that occurred in ≥10% of patients¹

FRUZAQLA had low Grade 3/4 laboratory abnormalities¹

Select laboratory abnormalities worsening from baseline and occurring in ≥20% of patients^1,a,b

Manageable safety profile with FRUZAQLA as demonstrated in the FRESCO trial^1,2

Clinical results with FRUZAQLA

Evolving patient unmet needs in mCRC

FRUZAQLA patient profiles

IMPORTANT SAFETY INFORMATION AND INDICATION

WARNINGS AND PRECAUTIONS

ADVERSE REACTIONS

DRUG INTERACTIONS

USE IN SPECIFIC POPULATIONS

INDICATION

Across multiple pivotal phase 3 clinical studies, FRUZAQLA demonstrated a manageable and predictable* safety profile.1-4

In FRESCO, the majority of ARs were manageable and predictable1-3

FRESCO was a single-country* study that evaluated fruquintinib safety and efficacy1,2

ARs that occurred in ≥10% of patients1

FRUZAQLA had low Grade 3/4 laboratory abnormalities1

Select laboratory abnormalities worsening from baseline and occurring in ≥20% of patients1,a,b

Manageable safety profile with FRUZAQLA as demonstrated in the FRESCO trial1,2

Clinical results with FRUZAQLA

Evolving patient unmet needs in mCRC

FRUZAQLA patient profiles

IMPORTANT SAFETY INFORMATION AND INDICATION

Across multiple pivotal phase 3 clinical studies, FRUZAQLA demonstrated a manageable and predictable* safety profile.^1-4

In FRESCO, the majority of ARs were manageable and predictable^1-3

FRESCO was a single-country* study that evaluated fruquintinib safety and efficacy^1,2

ARs that occurred in ≥10% of patients¹

FRUZAQLA had low Grade 3/4 laboratory abnormalities¹

Select laboratory abnormalities worsening from baseline and occurring in ≥20% of patients^1,a,b

Manageable safety profile with FRUZAQLA as demonstrated in the FRESCO trial^1,2