Inlyta 3mg

Inlyta 3mg is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) after failure of prior treatment with sunitinib or a cytokine.

Inlyta 3mg is a cancer medication that interferes with the growth and spread of cancer cells in the body.

Inlyta 3mg is used to treat cancer of the kidney.

Inlyta 3mg is usually given after other cancer medication has been tried without successful treatment.

Inlyta 3mg may also be used for purposes not listed in this medication guide.

The recommended starting oral dose is 5 mg twice daily. Inlyta 3mg may be taken with or without food.

If the patient vomits or misses a dose, an additional dose should not be taken. The next prescribed dose should be taken at the usual time.

Dose Adjustments: Dose increase or reduction is recommended based on individual safety and tolerability.

Patients who tolerate the Inlyta 3mg starting dose of 5 mg twice daily with no adverse reactions >grade 2 [according to the Common Toxicity Criteria for Adverse Events (CTCAE)] for 2 consecutive weeks, are normotensive, and are not receiving antihypertensive medication, may have their dose increased to 7 mg twice daily. Subsequently, using the same criteria, patients who tolerate the Inlyta 3mg dose of 7 mg twice daily, may have their dose increased to a maximum of 10 mg twice daily.

Management of some adverse drug reactions may require temporary or permanent discontinuation and/or dose reduction of Inlyta 3mg therapy. When dose reduction is necessary, the Inlyta 3mg dose may be reduced to 3 mg twice daily and further to 2 mg twice daily.

Dose adjustment is not required on the basis of patient age, race, gender or body weight.

Concomitant Strong CYP3A4/5 Inhibitors: Co-administration of Inlyta 3mg with strong CYP3A4/5 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin) may increase Inlyta 3mg plasma concentrations. Grapefruit may also increase Inlyta 3mg plasma concentrations. Selection of an alternate concomitant medication with no or minimal CYP3A4/5 inhibition potential is recommended. Although Inlyta 3mg dose adjustment has not been studied in patients receiving strong CYP3A4/5 inhibitors, if a strong CYP3A4/5 inhibitor must be co-administered, a dose decrease of Inlyta 3mg to approximately half the dose (eg, from a starting dose of 5 mg twice daily to a reduced dose of 2 mg twice daily) is recommended. If co-administration of the strong inhibitor is discontinued, a return to the Inlyta 3mg dose used prior to initiation of the strong CYP3A4/5 inhibitor should be considered.

Concomitant Strong CYP3A4/5 Inducers: Co-administration of Inlyta 3mg with strong CYP3A4/5 inducers [eg, rifampin, dexamethasone, phenytoin, carbamazepine, rifabutin, rifapentin, phenobarbital and Hypericum perforatum (also known as St. John’s wort)] may decrease Inlyta 3mg plasma concentrations. Selection of an alternate concomitant medication with no or minimal CYP3A4/5 induction potential is recommended. Although Inlyta 3mg dose adjustment has not been studied in patients receiving strong CYP3A4/5 inducers, if a strong CYP3A4/5 inducer must be co-administered, a gradual dose increase of Inlyta 3mg is recommended. If the dose of Inlyta 3mg is increased, the patient should be monitored carefully for toxicity. If co-administration of the strong inducer is discontinued, the Inlyta 3mg dose should be immediately returned to the dose used prior to initiation of the strong CYP3A4/5 inducer.

Hepatic Impairment: No dose adjustment is required when administering Inlyta 3mg to patients with mild hepatic impairment (Child-Pugh class A). A dose decrease is recommended when administering Inlyta 3mg to patients with moderate hepatic impairment (Child-Pugh class B) (eg, the starting dose should be reduced from 5-2 mg twice daily). Inlyta 3mg has not been studied in patients with severe hepatic impairment (Child-Pugh class C).

Renal Impairment: No dose adjustment is required.

Elderly: No dose adjustment is required.

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What is the most important information I should know about Inlyta 3mg?

Do not use Inlyta 3mg if you are pregnant. It could harm the unborn baby. Use birth control to prevent pregnancy while you are receiving Inlyta 3mg, whether you are a man or a woman. Inlyta 3mg use by either parent may cause birth defects or miscarriage.

You should not use Inlyta 3mg if you are allergic to it.

Before you take Inlyta 3mg, tell your doctor if you have liver or kidney disease, high blood pressure, a thyroid disorder, bleeding problems, an unhealed wound, stomach or intestinal bleeding, or a history of brain tumor, stroke, or blood clot.

Inlyta 3mg is usually taken once every 12 hours. Inlyta 3mg should be taken at evenly spaced intervals. Follow your doctor's instructions.

To be sure this medication is not causing harmful effects, your kidney, thyroid, and liver function will need to be tested. Your blood pressure will also need to be checked often. Visit your doctor regularly.

If you need surgery, tell the surgeon ahead of time that you are using Inlyta 3mg. You may need to stop using the medicine for a short time.

Stop using Inlyta 3mg and call your doctor at once if you have sudden weight loss, vision problems, confusion, sudden numbness or weakness, severe headache, feeling hot or cold, severe stomach pain, unusual bleeding, or seizure (convulsions).

Use Inlyta 3mg as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Inlyta 3mg. Talk to your pharmacist if you have questions about this information.
• Take Inlyta 3mg by mouth with or without food.
• Take each dose about 12 hours apart unless your doctor tells you otherwise.
• Swallow Inlyta 3mg whole with a glass of water. Do not break, crush, or chew before swallowing.
• Do not eat grapefruit or drink grapefruit juice while you use Inlyta 3mg.
• If you vomit after taking a dose of Inlyta 3mg, do not take an additional dose. Go back to your regular dosing schedule.
• If you miss a dose of Inlyta 3mg, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Inlyta 3mg.

Use: Labeled Indications

Renal cell carcinoma, advanced: Treatment of advanced renal cell carcinoma after failure of one prior systemic therapy.

Off Label Uses

Thyroid cancer (differentiated, advanced)

Data from a multi-center phase II study in patients with advanced differentiated (papillary, follicular, or Hurthle) thyroid cancer supports the use of Inlyta 3mg in the management of I.

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What other drugs will affect Inlyta 3mg?

In vitro data indicate that Inlyta 3mg is metabolised primarily by CYP3A4/5 and, to a lesser extent, CYP1A2, CYP2C19, and uridine diphosphate-glucuronosyltransferase (UGT) 1A1.

CYP3A4/5 Inhibitors: Ketoconazole, a strong inhibitor of CYP3A4/5, administered at a dose of 400 mg once daily for 7 days, increased the mean area under the curve (AUC) 2-fold and C_max 1.5-fold of a single 5-mg oral dose of Inlyta 3mg in healthy volunteers. Co-administration of Inlyta 3mg with strong CYP3A4/5 inhibitors (e.g. ketoconazole, itraconazole, clarithromycin, erythromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir and telithromycin) may increase Inlyta 3mg plasma concentrations. Grapefruit may also increase Inlyta 3mg plasma concentrations. Selection of concomitant medicinal products with no or minimal CYP3A4/5 inhibition potential is recommended. If a strong CYP3A4/5 inhibitor must be co-administered, a dose adjustment of Inlyta 3mg is recommended.

CYP1A2 and CYP2C19 Inhibitors: CYP1A2 and CYP2C19 constitute minor (<10%) pathways in Inlyta 3mg metabolism. The effect of strong inhibitors of these isozymes on Inlyta 3mg pharmacokinetics has not been studied. Caution should be exercised due to the risk of increased Inlyta 3mg plasma concentrations in patients taking strong inhibitors of these isozymes.

CYP3A4/5 Inducers: Rifampicin, a strong inducer of CYP3A4/5, administered at a dose of 600 mg once daily for 9 days, reduced the mean AUC by 79% and C_max by 71% of a single 5 mg dose of Inlyta 3mg in healthy volunteers.

Co-administration of Inlyta 3mg with strong CYP3A4/5 inducers [e.g. rifampicin, dexamethasone, phenytoin, carbamazepine, rifabutin, rifapentin, phenobarbital and Hypericum perforatum (St. John's wort)] may decrease Inlyta 3mg plasma concentrations. Selection of concomitant medicinal products with no or minimal CYP3A4/5 induction potential is recommended. If a strong CYP3A4/5 inducer must be co-administered, a dose adjustment of Inlyta 3mg is recommended.

In vitro Studies of CYP and UGT Inhibition and Induction: In vitro studies indicated that Inlyta 3mg does not inhibit CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4/5 or UGT1A1 at therapeutic plasma concentrations.

In vitro studies indicated that Inlyta 3mg has a potential to inhibit CYP1A2. Therefore, co-administration of Inlyta 3mg with CYP1A2 substrates may result in increased plasma concentrations of CYP1A2 substrates (e.g. theophylline).

In vitro

In vitro studies in human hepatocytes also indicated that Inlyta 3mg does not induce CYP1A1, CYP1A2 or CYP3A4/5. Therefore co-administration of Inlyta 3mg is not expected to reduce the plasma concentration of co-administered CYP1A1, CYP1A2 or CYP3A4/5 substrates in vivo.

In vitro Studies with P-Glycoprotein:

Therefore, co-administration of Inlyta 3mg is not expected to increase the plasma concentration of digoxin or other P-glycoprotein substrates, in vivo.

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What are the possible side effects of Inlyta 3mg?

Summary of the Safety Profile: The following risks, including appropriate action to be taken, are discussed in greater detail in Precautions: Cardiac failure events, hypertension, thyroid dysfunction, arterial thromboembolic events, venous thromboembolic events, elevation of haemoglobin or haematocrit, haemorrhage, gastrointestinal perforation and fistula formation, wound healing complications, PRES, proteinuria, and elevation of liver enzymes.

The most common (≥20%) adverse reactions observed following treatment with Inlyta 3mg were diarrhoea, hypertension, fatigue, decreased appetite, nausea, weight decreased, dysphonia, palmar-plantar erythrodysaesthesia (hand-foot) syndrome, haemorrhage, hypothyroidism, vomiting, proteinuria, cough, and constipation.

Tabulated List of Adverse Reactions: Table 2 presents adverse reactions reported in a pooled dataset of 672 patients who received Inlyta 3mg in clinical studies for the treatment of patients with RCC.

The adverse reactions are listed by system organ class, frequency category and grade of severity. Frequency categories are defined as: Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), and not known (cannot be estimated from the available data). The current safety database for Inlyta 3mg is too small to detect rare and very rare adverse reactions.

Categories have been assigned based on absolute frequencies in the clinical studies data. Within each system organ class, adverse reactions with the same frequency are presented in order of decreasing seriousness.

Description of Selected Adverse Reactions: Cardiac Failure Events : In a controlled clinical study with Inlyta 3mg (N=359) for the treatment of patients with RCC, cardiac failure events were reported in 1.7% patients receiving Inlyta 3mg, including cardiac failure (0.6%), cardiopulmonary failure (0.6%), left ventricular dysfunction (0.3%), and right ventricular failure (0.3%). Grade 4 cardiac failure adverse reactions were reported in 0.6% of patients receiving Inlyta 3mg. Fatal cardiac failure was reported in 0.6% of patients receiving Inlyta 3mg.

In monotherapy studies with Inlyta 3mg (N=672) for the treatment of patients with RCC, cardiac failure events (including cardiac failure, cardiac failure congestive, cardiopulmonary failure, left ventricular dysfunction, ejection fraction decreased, and right ventricular failure) were reported in 1.8% patients receiving Inlyta 3mg. Grade 3/4 cardiac failure events were reported in 1.0% patients and fatal cardiac failure events were reported in 0.3% patients receiving Inlyta 3mg.

Thyroid Dysfunction : In a controlled clinical study with Inlyta 3mg for the treatment of patients with RCC, hypothyroidism was reported in 20.9% of patients and hyperthyroidism was reported in 1.1% of patients. Thyroid stimulating hormone (TSH) increased was reported as an adverse reaction in 5.3% of patients receiving Inlyta 3mg. During routine laboratory assessments, in patients who had TSH <5 μU/ml before treatment, elevations of TSH to ≥10 μU/ml occurred in 32.2% of patients receiving Inlyta 3mg.

In pooled clinical studies with Inlyta 3mg (N=672) for the treatment of patients with RCC, hypothyroidism was reported in 24.6% of patients receiving Inlyta 3mg. Hyperthyroidism was reported in 1.6% of patients receiving Inlyta 3mg.

Venous Embolic and Thrombotic Events : In a controlled clinical study with Inlyta 3mg for the treatment of patients with RCC, venous embolic and thrombotic adverse reactions were reported in 3.9% of patients receiving Inlyta 3mg, including pulmonary embolism (2.2%), retinal vein occlusion/thrombosis (0.6%) and deep vein thrombosis (0.6%). Grade 3/4 venous embolic and thrombotic adverse reactions were reported in 3.1% of patients receiving Inlyta 3mg. Fatal pulmonary embolism was reported in one patient (0.3%) receiving Inlyta 3mg.

In pooled clinical studies with Inlyta 3mg (N=672) for the treatment of patients with RCC, venous embolic and thrombotic events were reported in 2.8% of patients receiving Inlyta 3mg. Grade 3 venous embolic and thrombotic events were reported in 0.9% of patients. Grade 4 venous embolic and thrombotic events were reported in 1.2% of patients. Fatal venous embolic and thrombotic events were reported 0.1% patients receiving Inlyta 3mg.

Arterial Embolic and Thrombotic Events : In a controlled clinical study with Inlyta 3mg for the treatment of patients with RCC, arterial embolic and thrombotic adverse reactions were reported in 4.7% of patients receiving Inlyta 3mg, including myocardial infarction (1.4%), transient ischemic attack (0.8%) and cerebrovascular accident (0.6%). Grade 3/4 arterial embolic and thrombotic adverse reactions were reported in 3.3% of patients receiving Inlyta 3mg. A fatal acute myocardial infarction and cerebrovascular accident was reported in one patient (0.3%) receiving Inlyta 3mg. In monotherapy studies with Inlyta 3mg (N=850), arterial embolic and thrombotic adverse reactions (including transient ischemic attack, myocardial infarction, and cerebrovascular accident) were reported in 5.3% of patients receiving Inlyta 3mg.

In pooled clinical studies with Inlyta 3mg (N=672) for the treatment of patients with RCC, arterial embolic and thrombotic events were reported in 2.8% of patients receiving Inlyta 3mg. Grade 3 arterial embolic and thrombotic events were reported in 1.2% of patients. Grade 4 arterial embolic and thrombotic events were reported in 1.3% of patients. Fatal arterial embolic and thrombotic events were reported in 0.3% patients receiving Inlyta 3mg.

Polycythaemia : In a controlled clinical study with Inlyta 3mg for the treatment of patients with RCC, polycythaemia was reported as an adverse reaction in 1.4% of patients receiving Inlyta 3mg. Routine laboratory assessments detected elevated haemoglobin above ULN in 9.7% of patients receiving Inlyta 3mg. In four clinical studies with Inlyta 3mg for the observed in 13.6% receiving Inlyta 3mg.

In pooled clinical studies with Inlyta 3mg (N=672) for the treatment of patients with RCC, polycythaemia was reported in 1.5% of patients receiving Inlyta 3mg.

Haemorrhage : In a controlled clinical study with Inlyta 3mg for the treatment of patients with RCC that excluded patients with untreated brain metastasis, haemorrhagic adverse reactions were reported in 21.4% of patients receiving Inlyta 3mg. The haemorrhagic adverse reactions in patients treated with Inlyta 3mg included epistaxis (7.8%), haematuria (3.6%), haemoptysis (2.5%), rectal haemorrhage (2.2%) and gingival bleeding (1.1%), gastric haemorrhage (0.6%), cerebral haemorrhage (0.3%) and lower gastrointestinal haemorrhage (0.3%). Grade ≥3 haemorrhagic adverse reactions were reported in 3.1% of patients receiving Inlyta 3mg (including cerebral haemorrhage, gastric haemorrhage and lower gastrointestinal haemorrhage and haemoptysis). Fatal haemorrhage was reported in one patient (0.3%) receiving Inlyta 3mg (gastric haemorrhage). In monotherapy studies with Inlyta 3mg (N=850), haemoptysis was reported in 3.9% of patients, Grade ≥3 haemoptysis was reported in 0.5% of patients.

In pooled clinical studies with Inlyta 3mg (N=672) for the treatment of patients with RCC, haemorrhagic events were reported in 25.7% of patients receiving Inlyta 3mg. Grade 3 haemorrhagic adverse reactions were reported in 3% of patients. Grade 4 haemorrhagic adverse reactions were reported in 1% of patients and fatal haemorrhage were reported in 0.4% of patients receiving Inlyta 3mg.

Gastrointestinal Perforation and Fistula Formation : In a controlled clinical study with Inlyta 3mg for the treatment of patients with RCC, gastrointestinal perforation-type events was reported in 1.7% of patients receiving Inlyta 3mg, including anal fistula (0.6%), fistula (0.3%) and gastrointestinal perforation (0.3%). In monotherapy studies with Inlyta 3mg (N=850), gastrointestinal perforation-type events were reported in 1.9% of patients and fatal gastrointestinal perforation was reported in one patient (0.1%).

In pooled clinical studies with Inlyta 3mg (N=672) for the treatment of patients with RCC, gastrointestinal perforation and fistula were reported in 1.9% of patients receiving Inlyta 3mg.

Reporting of Suspected Adverse Reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.

Inlyta 3mg (Inlyta 3mg) is a kinase inhibitor. Inlyta 3mg has the chemical name N-methyl-2-[3-((E)-2-pyridin-2-yl-vinyl)-1H-indazol-6-ylsulfanyl]-benzamide. The molecular formula is C₂₂H₁₈N₄OS and the molecular weight is 386.47 Daltons.

Inlyta 3mg is a white to light-yellow powder with a pKa of 4.8. The solubility of Inlyta 3mg in aqueous media over the range pH 1.1 to pH 7.8 is in excess of 0.2 μg/mL. The partition coefficient (n-octanol/water) is 3.5.

Excipients/Inactive Ingredients: Microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, magnesium stearate, and Opadry II red 32K15441. The Opadry II red 32K15441 film coating contains: Lactose monohydrate, HPMC 2910/Hypromellose 15cP, titanium dioxide, triacetin (glycerol triacetate), and red iron oxide.