Fotivda Side Effects Center

Last updated on RxList: 7/22/2021
Fotivda Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Fotivda?

Fotivda (tivozanib) is a kinase inhibitor indicated for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies.

What Are Side Effects of Fotivda?

Side effects of Fotivda include:

Dosage for Fotivda

The recommended dose of Fotivda is 1.34 mg once daily with or without food for 21 days on treatment followed by 7 days off treatment (28-day cycle) until disease progression or unacceptable toxicity.

Fotivda In Children

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

What Drugs, Substances, or Supplements Interact with Fotivda?

Fotivda may interact with other medicines such as:

  • strong CYP3A inducers

Tell your doctor all medications and supplements you use.

Fotivda During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Fotivda; it can harm a fetus. The pregnancy status of females of reproductive potential should be verified prior to starting treatment with Fotivda. Females of reproductive potential are advised to use effective contraception during treatment with Fotivda and for one month after the last dose. Males with female partners of reproductive potential are advised to use effective contraception during treatment with Fotivda and for one month after the last dose. It is unknown if Fotivda passes into breast milk. Because of the potential for serious adverse reactions in a breastfed child, breastfeeding is not recommended during treatment with Fotivda and for one month after the last dose.

Additional Information

Our Fotivda (tivozanib) 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.

Fotivda 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:

  • severe headache, confusion, dizziness;
  • a seizure;
  • chest pain, shortness of breath;
  • blurred vision, pounding in your neck or ears;
  • swelling in your lower legs, rapid weight gain;
  • any wound that will not heal;
  • easy bruising or bleeding (nosebleeds, bleeding gums);
  • signs of bleeding inside your body--weakness, dizziness; pink or brown urine; abnormal vaginal bleeding; bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds;
  • signs of a blood clot--sudden numbness or weakness on one side of the body, chest pain, problems with vision or speech, pain or swelling in an arm or leg; or
  • kidney problems--swelling, puffy eyes, foamy urine.

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

Common side effects may include:

  • nausea, vomiting, diarrhea, loss of appetite;
  • feeling weak or tired;
  • cough, hoarse voice;
  • mouth sores; or
  • abnormal blood tests.

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 Fotivda (Tivozanib Capsules)

Fotivda Professional Information

SIDE EFFECTS

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

  • Hypertension and Hypertensive Crisis [see WARNINGS AND PRECAUTIONS]
  • Cardiac Failure [see WARNINGS AND PRECAUTIONS]
  • Cardiac Ischemia and Arterial Thromboembolic Events [see WARNINGS AND PRECAUTIONS]
  • Venous Thromboembolic Events [see WARNINGS AND PRECAUTIONS]
  • Hemorrhagic Events [see WARNINGS AND PRECAUTIONS]
  • Proteinuria [see WARNINGS AND PRECAUTIONS]
  • Thyroid Dysfunction [see WARNINGS AND PRECAUTIONS]
  • Risk of Impaired Wound Healing [see WARNINGS AND PRECAUTIONS]
  • Reversible Posterior Leukoencephalopathy Syndrome (RPLS) [see WARNINGS AND PRECAUTIONS]

Clinical Trial Experience

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

The pooled safety population described in WARNINGS AND PRECAUTIONS reflect exposure to FOTIVDA administered at 1.34 mg orally once daily with or without food for 21 days on treatment followed by 7 days off treatment for a 28-day cycle in 1008 patients with advanced RCC in TIVO-3 and five other monotherapy studies. Among 1008 patients who received FOTIVDA, 52% were exposed for 6 months or longer and 34% were exposed for greater than one year.

Relapsed Or Refractory Advanced RCC Following Two Or More Prior Systemic Therapies

The safety of FOTIVDA was evaluated in TIVO-3, a randomized, open-label trial in 350 patients with relapsed or refractory advanced RCC who received 2 or 3 prior systemic treatments [see Clinical Studies]. Patients were randomized (1:1) to receive FOTIVDA 1.34 mg orally once daily for 21 days on treatment followed by 7 days off treatment for a 28-day cycle, or to receive sorafenib 400 mg orally twice a day continuously until disease progression or unacceptable toxicity. Among patients who received FOTIVDA, 53% were exposed for 6 months or longer and 31% were exposed for greater than one year.

Serious adverse reactions occurred in 45% of patients who received FOTIVDA. Serious adverse reactions in > 2% of patients included bleeding (3.5%), venous thromboembolism (3.5%), arterial thromboembolism (2.9%), acute kidney injury (2.3%), and hepatobiliary disorders (2.3%). Fatal adverse reactions occurred in 8% of patients who received FOTIVDA, including pneumonia (1.7%), hepatobiliary disorders (1.2%), respiratory failure (1.2%), myocardial infarction (0.6%), cerebrovascular accident (0.6%), and subdural hematoma (0.6%).

Permanent discontinuation of FOTIVDA due to an adverse reaction occurred in 21% of patients. Adverse reactions which resulted in permanent discontinuation of FOTIVDA in > 2 patients included hepatobiliary disorders, fatigue, and pneumonia.

Dosage interruptions of FOTIVDA due to an adverse reaction occurred in 48% of patients. Adverse reactions which required dosage interruption in > 5% of patients included fatigue, hypertension, decreased appetite, and nausea.

Dose reductions of FOTIVDA due to an adverse reaction occurred in 24% of patients. Adverse reactions which required dose reductions in > 3% of patients included fatigue, diarrhea, and decreased appetite.

The most common (≥ 20%) adverse reactions were fatigue, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis, and the most common Grade 3 or 4 laboratory abnormalities (≥ 5%) were sodium decreased, lipase increased, and phosphate decreased.

Table 2 summarizes the adverse reactions in TIVO-3.

Table 2: Adverse Reactions (≥ 15%) in Patients Who Received FOTIVDA in TIVO-3

Adverse Reaction FOTIVDA
(n = 173)
Sorafenib
(n = 170)
All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%)
Any 99 67 100 72
General
Fatigue* 67 13 48 12
Vascular
Hypertension† 44 24 31 17
Bleeding‡ 17 3 12 1
Gastrointestinal
Diarrhea§ 43 2 54 11
Nausea 30 0 18 4
Stomatitis 21 2 23 2
Vomiting 18 1 17 2
Metabolism and nutrition
Decreased appetite 39 5 30 4
Respiratory, thoracic, and mediastinal
Dysphonia 27 1 9 0
Cough 22 0 15 1
Dyspnea 15 3 11 1
Endocrine
Hypothyroidism¶ 24 1 11 0
Musculoskeletal
Back pain 19 2 16 2
Skin and subcutaneous tissue disorders
Rash# 18 1 52 15
Palmar-plantar erythrodysesthesia syndrome 16 1 41 17
Investigations
Weight decreased 17 3 22 3
* Includes fatigue and asthenia
† Includes hypertension, blood pressure increased, hypertensive crisis
‡ Includes hematuria, epistaxis, hemoptysis, hematoma, rectal hemorrhage, vaginal hemorrhage, contusion, gastrointestinal hemorrhage, hematochezia, intraocular hematoma, melena, metrorrhagia, pulmonary hemorrhage, subdural hematoma, gingival bleeding, hematemesis, hemorrhage intracranial, hemorrhoidal hemorrhage, splinter hemorrhages
§ Includes diarrhea and frequent bowel movements
¶ Includes hypothyroidism, blood thyroid stimulating hormone increased, tri-iodothyronine decreased, triiodothyronine free decreased
# Includes dermatitis, dermatitis acneiform, dermatitis contact, drug eruption, eczema, eczema nummular, erythema, erythema multiforme, photosensitivity reaction, pruritus, psoriasis, rash, rash erythematous, rash generalized, rash macular, rash maculo-papular, rash morbilliform, rash pruritic, seborrheic dermatitis, skin exfoliation, skin irritation, skin lesion, swelling face, toxic skin eruption, urticaria

Clinically relevant adverse reactions in < 15% of patients who received FOTIVDA included proteinuria, venous thromboembolism, arterial thromboembolism, hyperthyroidism, hepatobiliary disorders, osteonecrosis, cardiac failure, and delirium.

Table 3 summarizes the laboratory abnormalities in TIVO-3.

Table 3: Select Laboratory Abnormalities (≥ 10%) That Worsened from Baseline in Patients with Advanced RCC Who Received FOTIVDA

Laboratory Abnormality FOTIVDA1
(n = 173)
Sorafenib1
(n = 170)
All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%)
Hematology
Lymphocytes decreased 25 5 42 6
Hemoglobin increased 19 0 8 0
Platelets decreased 19 0 18 1
Hemoglobin decreased 16 1 27 4
Chemistry
Creatinine increased 50 0 37 1
Glucose increased 50 3 40 0
Phosphate decreased 38 5 63 31
Sodium decreased 36 9 30 11
Lipase increased 32 9 36 10
ALT increased 30 4 29 2
Alkaline phosphatase increased 30 4 32 2
AST increased 28 1 31 2
Potassium increased 26 3 23 0
Magnesium decreased 26 0 23 1
Amylase increased 23 2 28 3
Calcium increased 15 2 7 2
Bilirubin increased 11 3 11 0
Coagulation
Activated partial thromboplastin time prolonged 26 1 18 0
1 The denominator used to calculate the rate varied from 139 to 171 based on the number of patients with a baseline value and at least one post-treatment value.

DRUG INTERACTIONS

Effect Of Other Drugs On FOTIVDA

Strong CYP3A Inducers

Concomitant use of FOTIVDA with a strong CYP3A inducer decreases tivozanib exposure [see CLINICAL PHARMACOLOGY], which may reduce FOTIVDA anti-tumor activity.

Avoid concomitant use of strong CYP3A inducers with FOTIVDA.

Read the entire FDA prescribing information for Fotivda (Tivozanib Capsules)

© Fotivda Patient Information is supplied by Cerner Multum, Inc. and Fotivda Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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