TAVLESSE (Fostamatinib)
Spleen tyrosine kinase (SYK) inhibitor for chronic immune thrombocytopenia (ITP)
TAVLESSE (fostamatinib) is a prescription medicine used to treat adults with chronic immune thrombocytopenia (ITP) who have not responded adequately to previous treatments. It works by inhibiting spleen tyrosine kinase (SYK), reducing the immune-mediated destruction of platelets. This comprehensive guide covers dosage, side effects, drug interactions, warnings, and storage information based on EMA-approved prescribing information.
Quick Facts: TAVLESSE
Key Takeaways
- TAVLESSE is the first oral SYK inhibitor approved for chronic immune thrombocytopenia (ITP) in adults who have failed prior therapy
- Starting dose is 100 mg twice daily, which may be increased to 150 mg twice daily based on platelet response and tolerability
- Regular monitoring of blood pressure, liver function, and blood counts is essential during treatment
- TAVLESSE is contraindicated in pregnancy and women of childbearing potential must use effective contraception
- Common side effects include diarrhea, hypertension, abnormal liver tests, and dizziness — most can be managed with dose adjustments
What Is TAVLESSE and What Is It Used For?
TAVLESSE contains the active substance fostamatinib disodium hexahydrate, a first-in-class oral spleen tyrosine kinase (SYK) inhibitor. SYK is an enzyme that plays a pivotal role in the signaling pathways that lead to the antibody-mediated destruction of platelets (thrombocytes) by macrophages in the spleen and liver. By selectively targeting and inhibiting SYK, TAVLESSE reduces the phagocytic clearance of antibody-coated platelets, thereby helping to restore and maintain adequate platelet counts in the bloodstream.
Fostamatinib is actually a prodrug, meaning it is converted in the body to its active metabolite, known as R406. This active metabolite is responsible for the SYK-inhibiting activity that produces the therapeutic effect. R406 blocks the Fc-gamma receptor signaling in macrophages, which is the primary mechanism through which the immune system destroys platelets in ITP. This mechanism of action is distinct from other ITP treatments, as it targets the macrophage destruction pathway directly rather than stimulating platelet production or broadly suppressing the immune system.
TAVLESSE is specifically indicated for the treatment of chronic immune thrombocytopenia (ITP) in adult patients who have had an insufficient response to previous therapy. Chronic ITP is defined as ITP lasting more than 12 months from diagnosis. This autoimmune disorder is characterized by the body's own immune system producing antibodies that attack and destroy platelets in the blood. Platelets are essential blood cells responsible for blood clotting and stopping bleeding. When platelet counts drop too low (typically below 30,000 per microliter), patients are at significantly increased risk of spontaneous bruising, mucosal bleeding, and in severe cases, life-threatening hemorrhage.
In clinical trials, TAVLESSE demonstrated the ability to raise platelet counts to 50,000 per microliter or above in approximately 18% of patients with chronic ITP who had failed one or more prior lines of therapy. The FIT clinical trial program, which included the pivotal FIT-1 and FIT-2 studies, enrolled patients who had been previously treated with corticosteroids, thrombopoietin receptor agonists, rituximab, splenectomy, or other immunosuppressive agents. TAVLESSE was approved by the U.S. Food and Drug Administration (FDA) in April 2018 and by the European Medicines Agency (EMA) in January 2020, making it available to patients across multiple regulatory jurisdictions worldwide.
It is important to understand that TAVLESSE is not a cure for ITP but rather a treatment that helps control the condition by maintaining higher platelet counts. If treatment is discontinued, platelet counts typically return to pre-treatment levels. The decision to use TAVLESSE should be made in consultation with a hematologist experienced in the management of ITP, taking into account the patient's overall clinical picture, previous treatment history, and individual risk factors.
What Should You Know Before Taking TAVLESSE?
Before starting treatment with TAVLESSE, it is essential to have a thorough discussion with your healthcare provider about your complete medical history, current medications, and any planned surgeries or dental procedures. Your doctor will perform baseline assessments including blood pressure measurement, liver function tests, and a complete blood count to establish reference values for ongoing monitoring during treatment.
Contraindications
- You are allergic to fostamatinib or any of the other ingredients in this medicine
- You are pregnant or suspect you may be pregnant
TAVLESSE is absolutely contraindicated during pregnancy due to the potential for fetal harm and birth defects. Animal reproduction studies have shown adverse developmental effects at clinically relevant doses. There is no adequate data on the use of fostamatinib in pregnant women. If there is any possibility that you could be pregnant, your doctor should perform a pregnancy test before initiating treatment.
Hypersensitivity to the active substance or any of the excipients is also a contraindication. The excipients include mannitol, sodium hydrogen carbonate, sodium starch glycolate (type A), povidone (K30), and magnesium stearate, with the film coating containing polyvinyl alcohol, titanium dioxide, macrogol (3350), talc, yellow iron oxide, and red iron oxide.
Warnings and Precautions
Talk to your doctor or pharmacist before taking TAVLESSE, especially if you have any of the following conditions:
- High blood pressure (hypertension): New-onset or worsening hypertension is common in patients treated with TAVLESSE and can be severe. Your doctor will monitor your blood pressure regularly and may start or adjust blood pressure-lowering medication as needed. Seek immediate medical attention if you experience severe headache, confusion, dizziness, chest pain, or shortness of breath, as these may indicate a hypertensive crisis.
- Liver problems: Changes in liver function tests are common with TAVLESSE. Symptoms of liver damage include yellowing of the skin or eyes (jaundice), dark urine, pale stools, abdominal pain or swelling, swollen legs, persistent itching, chronic fatigue, nausea, vomiting, or loss of appetite. Your doctor will perform regular liver function tests during treatment.
- Diarrhea: Diarrhea is a very common side effect and can be severe in some cases. Your doctor may recommend dietary changes, increased fluid intake, or anti-diarrheal medication to manage symptoms. If diarrhea persists or becomes severe, dose reduction or temporary discontinuation may be necessary.
- Infections: TAVLESSE can reduce the number of white blood cells (neutropenia), which increases the risk of infections. Report any signs of infection promptly, including high fever, chills, sore throat, or general feeling of being unwell. Your doctor will monitor your white blood cell counts regularly.
Pregnancy and Breastfeeding
TAVLESSE must not be used during pregnancy. It may harm the unborn baby or cause birth defects. Women of childbearing potential must use reliable contraception during treatment and for at least 1 month after the last dose. Contact your doctor immediately if you become pregnant while taking TAVLESSE.
Breastfeeding is not recommended during treatment with TAVLESSE and for at least 1 month after the last dose. It is not known whether fostamatinib or its active metabolite R406 passes into breast milk, but based on the pharmacological activity and potential for serious adverse reactions in the nursing infant, the risk to the breastfed child cannot be excluded. If you are breastfeeding or planning to breastfeed, discuss the benefits and risks with your doctor before starting treatment.
TAVLESSE may impair female fertility. If you are concerned about your ability to conceive, discuss this with your healthcare provider before starting treatment. There are no data suggesting an effect on male fertility.
Children and Adolescents
TAVLESSE must not be used in patients under 18 years of age. The safety and efficacy of fostamatinib in children and adolescents have not been established. No clinical data are available for the pediatric population.
TAVLESSE 100 mg tablets contain 23 mg sodium per tablet (1.2% of the WHO recommended maximum daily intake of 2 g for adults). TAVLESSE 150 mg tablets contain 34 mg sodium per tablet (1.7% of the maximum daily intake). This should be taken into consideration by patients on a controlled sodium diet.
How Does TAVLESSE Interact with Other Drugs?
Drug interactions are an important consideration when taking TAVLESSE because fostamatinib and its active metabolite R406 affect several drug-metabolizing enzymes and transport proteins. R406 is primarily metabolized by CYP3A4, and it also inhibits CYP3A4, P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and organic anion transporting polypeptide 1B1 (OATP1B1). These interactions can alter the blood levels and effectiveness of both TAVLESSE and concomitant medications, potentially leading to increased side effects or reduced therapeutic benefit.
It is critical to inform your doctor about all medicines you are currently taking, have recently taken, or plan to take, including prescription medications, over-the-counter drugs, herbal supplements, and vitamins. Your doctor will assess the potential for interactions and may need to adjust doses or choose alternative medications where possible.
Major Interactions
| Drug | Therapeutic Class | Interaction Effect | Clinical Advice |
|---|---|---|---|
| Ketoconazole | Antifungal (CYP3A4 inhibitor) | Significantly increases fostamatinib exposure | Avoid co-administration or reduce TAVLESSE dose |
| Rifampicin | Antibiotic (CYP3A4 inducer) | Significantly decreases fostamatinib exposure | Avoid co-administration; reduced efficacy expected |
| Simvastatin | Statin (CYP3A4 substrate) | Increased simvastatin exposure; risk of myopathy | Consider dose reduction of simvastatin |
| Nelfinavir | HIV protease inhibitor | Increases fostamatinib exposure | Avoid co-administration or monitor closely |
| Anticoagulants | Blood thinners | Increased bleeding risk due to ITP and anticoagulant effects | Close monitoring of bleeding parameters required |
Other Notable Interactions
| Drug | Therapeutic Class | Interaction Effect | Clinical Advice |
|---|---|---|---|
| Rosuvastatin | Statin (BCRP substrate) | Increased rosuvastatin exposure via BCRP inhibition | Monitor for statin-related side effects |
| Digoxin | Cardiac glycoside (P-gp substrate) | Increased digoxin levels via P-gp inhibition | Monitor digoxin levels and adjust dose |
| Midazolam | Benzodiazepine (CYP3A4 substrate) | Increased midazolam exposure | Monitor for increased sedation |
| Verapamil | Calcium channel blocker | Potential increased verapamil exposure | Monitor blood pressure and heart rate |
| Ethinylestradiol | Oral contraceptive | Potential alteration in contraceptive levels | Consider additional contraceptive method |
| Pioglitazone | Antidiabetic (CYP2C8 substrate) | Potential increased pioglitazone exposure | Monitor blood glucose levels |
| Ranitidine | H2 receptor antagonist | Minimal clinical significance | No dose adjustment generally required |
The interaction with strong CYP3A4 inhibitors such as ketoconazole is of particular concern, as co-administration can lead to substantially higher plasma concentrations of the active metabolite R406, increasing the risk of dose-dependent side effects such as hypertension, hepatotoxicity, and neutropenia. Conversely, strong CYP3A4 inducers such as rifampicin can reduce fostamatinib exposure to a degree that may render the treatment ineffective.
Patients taking statins should be closely monitored, as TAVLESSE inhibits BCRP and CYP3A4, which can increase the blood levels of statins and raise the risk of muscle-related side effects (myopathy, rhabdomyolysis). Dose reduction of the statin may be necessary. Similarly, patients taking digoxin require monitoring of serum digoxin levels, as TAVLESSE's inhibition of P-glycoprotein can increase digoxin concentrations to potentially toxic levels.
What Is the Correct Dosage of TAVLESSE?
TAVLESSE dosing is individualized based on each patient's platelet count response and tolerability. Before starting treatment, your doctor will measure your baseline platelet count. The goal of therapy is to achieve and maintain a platelet count sufficient to reduce the risk of bleeding, typically at or above 50,000 per microliter. Your doctor will monitor your platelet count regularly throughout treatment to guide dose adjustments.
Adults
Starting Dose
100 mg taken orally twice daily (one 100 mg tablet in the morning and one in the evening). This is the standard starting dose for all adult patients.
Dose Escalation
After at least 4 weeks of treatment, if the platelet count has not increased to the target level and the patient is tolerating the medication well, the dose may be increased to 150 mg twice daily (one 150 mg tablet in the morning and one in the evening).
Maximum Dose
The maximum daily dose must not exceed 300 mg (150 mg twice daily). Higher doses have not been studied and are not recommended.
| Phase | Dose | Frequency | Duration |
|---|---|---|---|
| Initial treatment | 100 mg | Twice daily | Minimum 4 weeks |
| Dose escalation (if needed) | 150 mg | Twice daily | Ongoing |
| Maximum dose | 300 mg total daily | Divided into two doses | As directed by physician |
Patients with pre-existing liver problems or high blood pressure may require a lower starting dose. If you develop serious side effects such as severe hypertension, significant liver function test elevations, severe diarrhea, or low white blood cell counts, your doctor may reduce your dose or temporarily or permanently discontinue treatment. If TAVLESSE does not produce an adequate platelet response, your doctor will discontinue the medication.
How to Take TAVLESSE
Swallow the tablets whole with water. Do not crush, break, or chew the tablets. TAVLESSE can be taken with food or between meals. If you experience stomach upset, taking the tablets with food may help reduce gastrointestinal symptoms. Try to take your doses at approximately the same times each day to maintain consistent blood levels of the medication.
Children
TAVLESSE is not approved for use in patients under 18 years of age. The safety and efficacy in the pediatric population have not been established through clinical trials.
Elderly Patients
No dose adjustment is required solely based on age. However, elderly patients are more likely to have reduced kidney or liver function and are at greater risk of hypertension, so more frequent monitoring may be appropriate. Dose adjustments should be based on individual tolerability and clinical response.
Missed Dose
Do not take a double dose to make up for a missed one. Simply take the next dose at your regular scheduled time. If you feel nauseous after taking a dose, do not take an additional tablet. Wait and take the next dose as scheduled.
Overdose
If you have taken more TAVLESSE than prescribed, contact your doctor or pharmacist immediately, or go to the nearest emergency department. There is no specific antidote for fostamatinib overdose. Treatment is supportive and symptomatic.
It is important to continue taking TAVLESSE for as long as your doctor prescribes it. Do not stop taking the medication without consulting your doctor, as abruptly discontinuing treatment will likely cause your platelet count to drop back to pre-treatment levels, potentially increasing your bleeding risk.
What Are the Side Effects of TAVLESSE?
Like all medicines, TAVLESSE can cause side effects, although not everybody gets them. The side effects listed below are based on data from clinical trials and post-marketing surveillance. The frequency and severity of side effects can vary significantly between individuals, and many side effects are manageable with dose adjustments or supportive care.
Serious Side Effects
- Hypertensive crisis: Severe headache, confusion, dizziness, chest pain — may lead to stroke
- Febrile neutropenia: High fever with signs of infection associated with low white blood cell count
- Pneumonia: Shortness of breath, chest pain, productive cough with discolored sputum
- Severe liver damage: Yellowing of skin/eyes (jaundice), dark urine, pale stools, severe abdominal pain
- Severe diarrhea: Persistent, watery diarrhea that does not respond to initial management
Side Effects by Frequency
Very Common
- Diarrhea, nausea, vomiting, and frequent bowel movements
- High blood pressure (hypertension)
- Abnormal liver function blood test results
- Dizziness
Common
- Low white blood cell count (neutropenia)
- Abdominal (stomach) pain
- Chest pain
- Fatigue (tiredness, exhaustion)
- Flu-like symptoms
- Upper respiratory tract infections (sore throat, common cold)
- Bronchitis (respiratory tract infection)
- Taste changes (dysgeusia)
- Skin rash
- Headache
High blood pressure is one of the most clinically significant side effects of TAVLESSE. In clinical trials, approximately 28% of patients experienced new-onset or worsening hypertension. Blood pressure should be monitored before initiating treatment and at regular intervals thereafter. Most cases of hypertension can be managed with standard antihypertensive medications, but in some cases, dose reduction or discontinuation of TAVLESSE may be necessary.
Liver function test abnormalities occurred in approximately 10-15% of patients in clinical trials. These are typically asymptomatic elevations detected through routine blood monitoring, but they can occasionally progress to clinically significant hepatotoxicity. Monthly liver function monitoring is recommended during the first several months of treatment and periodically thereafter.
Diarrhea is the most frequently reported gastrointestinal side effect, occurring in approximately 31% of patients. In most cases, it is mild to moderate in severity and can be managed with dietary modifications (avoiding dairy, high-fiber, and spicy foods), adequate hydration, and over-the-counter anti-diarrheal medications. Severe diarrhea may require dose reduction.
Neutropenia (low white blood cell count) is an important safety concern as it can increase susceptibility to infections. Regular monitoring of complete blood counts allows early detection of neutropenia. If your white blood cell count drops below a certain threshold, your doctor may temporarily pause treatment until it recovers. Be vigilant for signs of infection, such as fever, sore throat, or persistent malaise, and report them promptly.
It is important to report suspected side effects after a medicine has been authorized. This allows continued monitoring of the benefit-risk balance of the medicine. Healthcare professionals and patients can report suspected adverse reactions to their national pharmacovigilance authority.
How Should You Store TAVLESSE?
Proper storage of TAVLESSE is essential to ensure the medication remains effective and safe throughout its shelf life. Store the tablets in the original container with the lid tightly closed. The container includes two desiccant packets to absorb moisture — do not remove these desiccants. There are no special temperature requirements, meaning the medication can be stored at normal room temperature.
Keep this medicine out of the sight and reach of children. Do not use TAVLESSE after the expiry date stated on the carton and the container after "EXP". The expiry date refers to the last day of that month. Once the container has been opened, use the tablets within the specified timeframe as directed by your pharmacist.
Do not dispose of medicines in wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer needed. Proper disposal helps protect the environment and prevents accidental ingestion by others.
What Does TAVLESSE Contain?
Understanding the full composition of your medication can be important, especially if you have known allergies or sensitivities to specific pharmaceutical ingredients. Below is the complete list of ingredients in TAVLESSE tablets.
Active Ingredient
Fostamatinib disodium hexahydrate — available in two strengths: 100 mg and 150 mg per tablet. This is a prodrug that is converted to the active metabolite R406 after oral administration.
Inactive Ingredients (Excipients)
- Tablet core: Mannitol, sodium hydrogen carbonate, sodium starch glycolate (type A), povidone (K30), magnesium stearate
- Film coating: Polyvinyl alcohol, titanium dioxide, macrogol (3350), talc, yellow iron oxide, red iron oxide
Tablet Appearance
| Strength | Shape | Color | Imprint | Pack Sizes |
|---|---|---|---|---|
| 100 mg | Round, biconvex | Dark orange | "R" on one side, "100" on the other | Bottles of 30 or 60 |
| 150 mg | Oval, biconvex | Light orange | "R" on one side, "150" on the other | Bottles of 30 or 60 |
Each bottle contains 2 desiccant packets to protect against moisture. Not all pack sizes may be marketed in all countries. The marketing authorization holder is Instituto Grifols, S.A., based in Barcelona, Spain.
Frequently Asked Questions About TAVLESSE
Medical References
Peer-Reviewed Sources & International Guidelines
- European Medicines Agency (EMA) (2020). "TAVLESSE (fostamatinib) – Summary of Product Characteristics." EMA-approved prescribing information for fostamatinib in the European Union.
- U.S. Food and Drug Administration (FDA) (2018). "TAVALISSE (fostamatinib disodium hexahydrate) – Full Prescribing Information." FDA-approved prescribing information for fostamatinib in the United States.
- Bussel J, et al. (2018). "Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: Results of two phase 3, randomized, placebo-controlled trials." American Journal of Hematology. 93(7):921-930. Pivotal FIT-1 and FIT-2 clinical trial results. Evidence level: 1A
- Bussel JB, et al. (2019). "Long-term fostamatinib treatment of adults with immune thrombocytopenia during the phase 3 clinical trial program." American Journal of Hematology. 94(5):546-553. Long-term safety and efficacy data from the FIT clinical trial extension.
- Neunert C, et al. (2019). "American Society of Hematology 2019 guidelines for immune thrombocytopenia." Blood Advances. 3(23):3829-3866. ASH clinical practice guidelines for ITP management including newer agents.
- Provan D, et al. (2019). "Updated international consensus report on the investigation and management of primary immune thrombocytopenia." Blood Advances. 3(22):3780-3817. International consensus guidelines for ITP diagnosis and treatment.
Evidence grading: This article uses the GRADE framework (Grading of Recommendations Assessment, Development and Evaluation) for evidence-based medicine. Evidence level 1A represents the highest quality of evidence, based on systematic reviews of randomized controlled trials.
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