Fotivda 0.89mg Capsules
It is used to treat kidney cancer.
Drug Class
Antineoplastic
Pharmacologic Class
Tyrosine Kinase Inhibitor (TKI); Vascular Endothelial Growth Factor (VEGF) Receptor Inhibitor
Pregnancy Category
Not available
FDA Approved
Mar 2021
DEA Schedule
Not Controlled
Overview
What is this medicine?
Fotivda is an oral medication used to treat advanced kidney cancer. It works by blocking certain proteins (VEGF receptors) that help cancer cells grow and form new blood vessels, which are essential for the tumor to survive and spread.
How to Use This Medicine
Taking Your Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. Take the medication with or without food, swallowing the capsules whole with a full glass of water. Do not open the capsules.
Storing and Disposing of Your Medication
Store the medication at room temperature in a dry location, avoiding the bathroom. Keep all medications in a safe place, out of the reach of children and pets.
Missing a Dose
If you miss a dose, skip it and resume your normal dosing schedule. Do not take two doses on the same day to make up for the missed dose.
To use this medication correctly, follow your doctor's instructions and read all the information provided. Take the medication with or without food, swallowing the capsules whole with a full glass of water. Do not open the capsules.
Storing and Disposing of Your Medication
Store the medication at room temperature in a dry location, avoiding the bathroom. Keep all medications in a safe place, out of the reach of children and pets.
Missing a Dose
If you miss a dose, skip it and resume your normal dosing schedule. Do not take two doses on the same day to make up for the missed dose.
Lifestyle & Tips
- Take Fotivda exactly as prescribed, usually once daily for 21 days, followed by 7 days off.
- Swallow capsules whole with water; do not open, crush, or chew them.
- Take with or without food.
- Monitor your blood pressure regularly at home as instructed by your doctor.
- Report any new or worsening side effects to your healthcare provider promptly.
- Avoid grapefruit and grapefruit juice as they may interact with this medication.
- Use effective contraception during treatment and for at least 2 weeks after the last dose if you are a woman of childbearing potential or a male with a female partner of childbearing potential.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
1.34 mg orally once daily for 21 days, followed by 7 days off, for a 28-day cycle. (Note: Fotivda is available in 0.89 mg and 1.34 mg capsules. The 0.89 mg capsule is used for dose reductions.)
Dose Range:
0.89 - 1.34 mg
Condition-Specific Dosing:
Renal Cell Carcinoma (RCC):
1.34 mg orally once daily for 21 days, followed by 7 days off, for a 28-day cycle.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment required
Moderate:
No dose adjustment required
Severe:
Not available (limited data)
Dialysis:
Not available (limited data)
Hepatic Impairment:
Mild:
No dose adjustment required
Moderate:
No dose adjustment required
Severe:
Not studied (avoid use if possible)
Pharmacology
Mechanism of Action
Tivozanib is a tyrosine kinase inhibitor (TKI) that selectively inhibits vascular endothelial growth factor (VEGF) receptors 1, 2, and 3. By inhibiting these receptors, tivozanib blocks angiogenesis (formation of new blood vessels) and tumor cell proliferation, which are critical processes for tumor growth and metastasis.
Pharmacokinetics
Absorption:
Bioavailability:
Not explicitly stated as a percentage, but well absorbed
Tmax:
2 to 24 hours (median 12 hours)
FoodEffect:
No clinically significant effect of food on tivozanib exposure
Distribution:
Vd:
Approximately 1000 L (high volume of distribution)
ProteinBinding:
>99%
CnssPenetration:
Limited (though some activity observed in brain metastases in clinical studies)
Elimination:
HalfLife:
Approximately 4.5 to 5 days
Clearance:
Approximately 1.5 L/hour
ExcretionRoute:
Primarily fecal (approximately 65%), followed by renal (approximately 25%)
Unchanged:
<1% (in urine)
Pharmacodynamics
OnsetOfAction:
Not acutely measurable for anti-tumor effect; related to sustained VEGF receptor inhibition
PeakEffect:
Not acutely measurable for anti-tumor effect
DurationOfAction:
Prolonged due to long half-life and sustained target inhibition
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:
Allergic Reaction: Rash, hives, itching, redness, swelling, blistering, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, difficulty breathing, swallowing, or speaking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
High Blood Pressure: Severe headache, dizziness, fainting, or changes in vision.
Bleeding: Vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, gum bleeding, abnormal vaginal bleeding, unexplained bruises or bruising that worsens, or uncontrollable bleeding.
Kidney Problems: Inability to urinate, changes in urine output, blood in the urine, or sudden weight gain.
Liver Problems: Dark urine, fatigue, decreased appetite, stomach upset or pain, light-colored stools, vomiting, or yellowing of the skin and eyes.
High Blood Sugar: Confusion, drowsiness, increased thirst or hunger, frequent urination, flushing, rapid breathing, or fruity-smelling breath.
Thyroid Problems: Weight changes, nervousness, excitability, restlessness, weakness, hair thinning, depression, eye or neck swelling, difficulty concentrating, heat or cold intolerance, menstrual changes, shakiness, or sweating.
Electrolyte Imbalance: Mood changes, confusion, muscle pain, cramps, or spasms, weakness, shakiness, balance problems, abnormal heartbeat, seizures, loss of appetite, or severe stomach upset or vomiting.
Skin Reactions: Redness or irritation on the palms of the hands or soles of the feet.
Posterior Reversible Encephalopathy Syndrome (PRES): A rare but potentially life-threatening brain condition. Seek immediate medical attention if you experience confusion, decreased alertness, vision changes, loss of vision, seizures, or severe headache.
Blood Clots: Chest, arm, back, neck, or jaw pain or pressure, coughing up blood, numbness or weakness on one side of the body, speech or thinking difficulties, balance problems, vision changes, shortness of breath, or swelling, warmth, or pain in the leg or arm.
Heart Failure: Shortness of breath, sudden weight gain, swelling in the arms or legs, or bulging neck veins. Although rare, heart failure can be life-threatening.
Gastrointestinal Perforation or Fistula: Severe stomach pain or swelling, black, tarry, or bloody stools, or high fever. These conditions can be life-threatening.
Other Possible Side Effects
While many people may not experience side effects or may only have mild side effects, it's essential to be aware of the following:
Fatigue or weakness
Diarrhea, stomach upset, or vomiting
Decreased appetite
Cough
Mouth irritation or mouth sores
Voice changes
Back pain
* Weight loss
If you experience any of these side effects or have concerns about other symptoms, contact your doctor for guidance. Not all possible side effects are listed here. If you have questions or concerns, consult your doctor or report side effects to the FDA at 1-800-332-1088 or https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:
Allergic Reaction: Rash, hives, itching, redness, swelling, blistering, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, difficulty breathing, swallowing, or speaking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
High Blood Pressure: Severe headache, dizziness, fainting, or changes in vision.
Bleeding: Vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, gum bleeding, abnormal vaginal bleeding, unexplained bruises or bruising that worsens, or uncontrollable bleeding.
Kidney Problems: Inability to urinate, changes in urine output, blood in the urine, or sudden weight gain.
Liver Problems: Dark urine, fatigue, decreased appetite, stomach upset or pain, light-colored stools, vomiting, or yellowing of the skin and eyes.
High Blood Sugar: Confusion, drowsiness, increased thirst or hunger, frequent urination, flushing, rapid breathing, or fruity-smelling breath.
Thyroid Problems: Weight changes, nervousness, excitability, restlessness, weakness, hair thinning, depression, eye or neck swelling, difficulty concentrating, heat or cold intolerance, menstrual changes, shakiness, or sweating.
Electrolyte Imbalance: Mood changes, confusion, muscle pain, cramps, or spasms, weakness, shakiness, balance problems, abnormal heartbeat, seizures, loss of appetite, or severe stomach upset or vomiting.
Skin Reactions: Redness or irritation on the palms of the hands or soles of the feet.
Posterior Reversible Encephalopathy Syndrome (PRES): A rare but potentially life-threatening brain condition. Seek immediate medical attention if you experience confusion, decreased alertness, vision changes, loss of vision, seizures, or severe headache.
Blood Clots: Chest, arm, back, neck, or jaw pain or pressure, coughing up blood, numbness or weakness on one side of the body, speech or thinking difficulties, balance problems, vision changes, shortness of breath, or swelling, warmth, or pain in the leg or arm.
Heart Failure: Shortness of breath, sudden weight gain, swelling in the arms or legs, or bulging neck veins. Although rare, heart failure can be life-threatening.
Gastrointestinal Perforation or Fistula: Severe stomach pain or swelling, black, tarry, or bloody stools, or high fever. These conditions can be life-threatening.
Other Possible Side Effects
While many people may not experience side effects or may only have mild side effects, it's essential to be aware of the following:
Fatigue or weakness
Diarrhea, stomach upset, or vomiting
Decreased appetite
Cough
Mouth irritation or mouth sores
Voice changes
Back pain
* Weight loss
If you experience any of these side effects or have concerns about other symptoms, contact your doctor for guidance. Not all possible side effects are listed here. If you have questions or concerns, consult your doctor or report side effects to the FDA at 1-800-332-1088 or https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Severe headache, dizziness, blurred vision, or nosebleeds (signs of high blood pressure)
- Unusual bleeding or bruising (e.g., blood in urine/stools, severe nosebleeds, coughing up blood)
- Chest pain, shortness of breath, sudden numbness or weakness, severe leg pain or swelling (signs of blood clots or heart problems)
- Severe abdominal pain, fever, or persistent nausea/vomiting (signs of GI perforation or fistula)
- Yellowing of skin or eyes, dark urine, severe nausea/vomiting, or pain in the upper right abdomen (signs of liver problems)
- Extreme fatigue, weight gain, feeling cold, or hoarseness (signs of thyroid problems)
- Foamy urine or significant swelling in hands/feet/ankles (signs of kidney problems/proteinuria)
- Redness, swelling, or pain on the palms of hands or soles of feet (hand-foot syndrome)
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
Certain health conditions, such as high blood pressure or thyroid problems, that you are currently being treated for or have a history of.
* Any medications you are taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins. This is crucial because some medications, such as those used to treat HIV, infections, seizures, and other conditions, may interact with this medication and should not be taken together.
Additionally, if you are breast-feeding, please note that you should not breast-feed while taking this medication or for 1 month after your last dose.
To ensure your safety, it is crucial to provide your doctor and pharmacist with a comprehensive list of all your medications, including prescription and OTC drugs, natural products, and vitamins, as well as any health problems you have. This will help them determine whether it is safe for you to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
Certain health conditions, such as high blood pressure or thyroid problems, that you are currently being treated for or have a history of.
* Any medications you are taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins. This is crucial because some medications, such as those used to treat HIV, infections, seizures, and other conditions, may interact with this medication and should not be taken together.
Additionally, if you are breast-feeding, please note that you should not breast-feed while taking this medication or for 1 month after your last dose.
To ensure your safety, it is crucial to provide your doctor and pharmacist with a comprehensive list of all your medications, including prescription and OTC drugs, natural products, and vitamins, as well as any health problems you have. This will help them determine whether it is safe for you to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. If you experience gastrointestinal side effects such as stomach upset, vomiting, diarrhea, or decreased appetite, consult your doctor, as there may be ways to minimize these effects.
Regular blood tests and other laboratory assessments, as directed by your doctor, are crucial to monitor your condition. This medication may cause hypertension, so it is vital to have your blood pressure checked as advised by your doctor. If you have diabetes, you will need to closely monitor your blood sugar levels.
Be aware that this medication may increase your risk of bleeding. To minimize this risk, be cautious and avoid injuries. Use a soft-bristled toothbrush and an electric razor. Although rare, some bleeding complications can be life-threatening.
This medication may also affect wound healing. If you require surgery, your doctor may instruct you to stop taking this medication before the procedure and resume it afterward. Immediately contact your doctor if you experience any wound healing problems or other wound-related issues.
If you are allergic to tartrazine (FD&C Yellow No. 5), discuss this with your doctor, as some formulations of this medication may contain this ingredient.
This medication may impact fertility, potentially leading to difficulties in becoming pregnant or fathering a child. If you plan to conceive, consult your doctor before starting this medication.
Due to the potential risk of harm to an unborn baby, a pregnancy test will be conducted before initiating this medication to confirm that you are not pregnant. If you may become pregnant, use effective birth control during treatment and for one month after your last dose. If you become pregnant, notify your doctor immediately.
Similarly, if your partner may become pregnant, use birth control during your treatment and for one month after your last dose. If your partner becomes pregnant, contact the doctor right away.
Regular blood tests and other laboratory assessments, as directed by your doctor, are crucial to monitor your condition. This medication may cause hypertension, so it is vital to have your blood pressure checked as advised by your doctor. If you have diabetes, you will need to closely monitor your blood sugar levels.
Be aware that this medication may increase your risk of bleeding. To minimize this risk, be cautious and avoid injuries. Use a soft-bristled toothbrush and an electric razor. Although rare, some bleeding complications can be life-threatening.
This medication may also affect wound healing. If you require surgery, your doctor may instruct you to stop taking this medication before the procedure and resume it afterward. Immediately contact your doctor if you experience any wound healing problems or other wound-related issues.
If you are allergic to tartrazine (FD&C Yellow No. 5), discuss this with your doctor, as some formulations of this medication may contain this ingredient.
This medication may impact fertility, potentially leading to difficulties in becoming pregnant or fathering a child. If you plan to conceive, consult your doctor before starting this medication.
Due to the potential risk of harm to an unborn baby, a pregnancy test will be conducted before initiating this medication to confirm that you are not pregnant. If you may become pregnant, use effective birth control during treatment and for one month after your last dose. If you become pregnant, notify your doctor immediately.
Similarly, if your partner may become pregnant, use birth control during your treatment and for one month after your last dose. If your partner becomes pregnant, contact the doctor right away.
Overdose Information
Overdose Symptoms:
- Exaggerated known adverse reactions (e.g., severe hypertension, fatigue, diarrhea, proteinuria, thyroid dysfunction)
What to Do:
There is no specific antidote for tivozanib overdose. Management should consist of general supportive measures and treatment of symptoms. Call 1-800-222-1222 (Poison Control Center) for advice.
Drug Interactions
Contraindicated Interactions
- Strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's wort)
Major Interactions
- Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir, itraconazole, grapefruit juice) - may require tivozanib dose reduction
Moderate Interactions
- Moderate CYP3A4 inhibitors/inducers
- P-glycoprotein (P-gp) inhibitors/inducers (clinical significance less clear)
Minor Interactions
- Not available
Monitoring
Baseline Monitoring
Blood Pressure
Rationale: Risk of hypertension, a common and potentially severe adverse reaction.
Timing: Prior to initiation of treatment
Thyroid Function Tests (TSH, free T4)
Rationale: Risk of hypothyroidism.
Timing: Prior to initiation of treatment
Urinalysis for Proteinuria
Rationale: Risk of proteinuria, including nephrotic syndrome.
Timing: Prior to initiation of treatment
Liver Function Tests (ALT, AST, bilirubin)
Rationale: Risk of hepatotoxicity.
Timing: Prior to initiation of treatment
Electrolytes (Potassium, Magnesium, Calcium)
Rationale: Risk of electrolyte abnormalities.
Timing: Prior to initiation of treatment
Routine Monitoring
Blood Pressure
Frequency: Weekly for the first month, then at least monthly thereafter, or as clinically indicated.
Target: <140/90 mmHg (or individualized target)
Action Threshold: Hypertension requiring medical management or dose modification/interruption.
Thyroid Function Tests (TSH, free T4)
Frequency: Monthly for the first 6 months, then every 3 months thereafter, or as clinically indicated.
Target: Within normal limits
Action Threshold: Hypothyroidism requiring thyroid hormone replacement or dose modification/interruption.
Urinalysis for Proteinuria
Frequency: Monthly for the first 6 months, then every 3 months thereafter, or as clinically indicated.
Target: Negative or trace protein
Action Threshold: Proteinuria âĨ 2+ or >1 g/24 hours requiring dose modification/interruption.
Liver Function Tests (ALT, AST, bilirubin)
Frequency: Monthly for the first 6 months, then every 3 months thereafter, or as clinically indicated.
Target: Within normal limits
Action Threshold: Elevations (e.g., >3x ULN) requiring dose modification/interruption.
Electrolytes (Potassium, Magnesium, Calcium)
Frequency: Monthly for the first 6 months, then every 3 months thereafter, or as clinically indicated.
Target: Within normal limits
Action Threshold: Significant abnormalities requiring correction or dose modification/interruption.
Complete Blood Count (CBC)
Frequency: Periodically, or as clinically indicated.
Target: Within normal limits
Action Threshold: Significant cytopenias.
Symptom Monitoring
- Hypertension (headache, dizziness, blurred vision)
- Fatigue
- Diarrhea
- Nausea/Vomiting
- Dysphonia (hoarseness)
- Decreased appetite
- Hypothyroidism (fatigue, weight gain, cold intolerance)
- Proteinuria (foamy urine, swelling)
- Hand-foot syndrome (redness, swelling, pain on palms/soles)
- Arterial/venous thrombotic events (chest pain, shortness of breath, leg swelling, numbness/weakness)
- Hemorrhage (unusual bleeding or bruising)
- Cardiac dysfunction (shortness of breath, swelling, palpitations)
- Fistula formation (unusual discharge, pain)
- Gastrointestinal perforation (severe abdominal pain, fever)
Special Patient Groups
Pregnancy
Fotivda can cause fetal harm when administered to a pregnant woman based on animal studies and its mechanism of action. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment and for 2 weeks after the last dose.
Trimester-Specific Risks:
First Trimester:
Potential for major birth defects and miscarriage due to mechanism of action (VEGF inhibition).
Second Trimester:
Potential for fetal harm, including effects on vascular development and organogenesis.
Third Trimester:
Potential for fetal harm, including effects on vascular development and growth.
Lactation
It is not known if tivozanib is excreted in human milk. Due to the potential for serious adverse reactions in a breastfed infant, advise women not to breastfeed during treatment with Fotivda and for 2 weeks after the last dose.
Infant Risk:
High (potential for serious adverse reactions)
Pediatric Use
The safety and effectiveness of Fotivda in pediatric patients have not been established.
Geriatric Use
No overall differences in safety or effectiveness were observed between patients âĨ65 years of age and younger patients. No specific dose adjustment is required based on age, but monitor for age-related comorbidities and polypharmacy.
Clinical Information
Clinical Pearls
- Tivozanib has a long half-life, leading to sustained drug exposure and target inhibition. This also means side effects can persist after discontinuation.
- Hypertension is a common and early side effect; monitor blood pressure closely and manage aggressively to prevent complications.
- Hypothyroidism is also common; monitor thyroid function and initiate hormone replacement as needed.
- Proteinuria can occur; regular urinalysis is crucial. Dose modifications may be necessary for significant proteinuria.
- Patients should be educated on the importance of adherence to the 21-day on, 7-day off dosing schedule.
- Counsel patients on potential for hand-foot syndrome and strategies for management (e.g., moisturizers, avoiding friction/pressure).
Alternative Therapies
- Cabozantinib (Cabometyx)
- Lenvatinib (Lenvima)
- Sunitinib (Sutent)
- Pazopanib (Votrient)
- Axitinib (Inlyta)
- Pembrolizumab (Keytruda) + Lenvatinib (Lenvima)
- Nivolumab (Opdivo) + Cabozantinib (Cabometyx)
- Belzutifan (Welireg)
Cost & Coverage
Average Cost:
Typically >$20,000 - $25,000 per 21 capsules (1.34mg)
Insurance Coverage:
Specialty Tier (requires prior authorization, often subject to high co-pays or co-insurance)
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so be sure to check with your pharmacist for more information. If you have any questions or concerns about this medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek medical attention. When seeking help, be prepared to provide details about the medication, including the amount taken and the time it happened, to ensure you receive the best possible care.