INLYTA

INLYTA- axitinib tablet, film coated
Pfizer Laboratories Div Pfizer Inc

1 INDICATIONS AND USAGE

1.1 First-Line Advanced Renal Cell Carcinoma

INLYTA in combination with avelumab is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

INLYTA in combination with pembrolizumab is indicated for the first-line treatment of patients with advanced RCC.

1.2 Second-Line Advanced Renal Cell Carcinoma

INLYTA as a single agent is indicated for the treatment of advanced RCC after failure of one prior systemic therapy.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosing

First-Line Advanced RCC

INLYTA in Combination with Avelumab

​ The recommended starting dosage of INLYTA is 5 mg orally taken twice daily (12 hours apart) with or without food in combination with avelumab 800 mg administered as an intravenous infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity. When INLYTA is used in combination with avelumab, dose escalation of INLYTA above the initial 5 mg dose may be considered at intervals of two weeks or longer. Review the Full Prescribing Information for recommended avelumab dosing information.

INLYTA in Combination with Pembrolizumab

​ The recommended starting dosage of INLYTA is 5 mg orally twice daily (12 hours apart) with or without food in combination with pembrolizumab 200 mg every 3 weeks or 400 mg every 6 weeks administered as an intravenous infusion over 30 minutes until disease progression or unacceptable toxicity. When INLYTA is used in combination with pembrolizumab, dose escalation of INLYTA above the initial 5 mg dose may be considered at intervals of six weeks or longer. Review the Full Prescribing Information for recommended pembrolizumab dosing information.

Second-Line Advanced RCC

When INLYTA is used as a single agent, the recommended starting oral dose is 5 mg twice daily. Administer INLYTA doses approximately 12 hours apart with or without food.

Important Administration Instructions

Advise patients to swallow INLYTA whole with a full glass of water. If the patient vomits or misses a dose, an additional dose should not be taken. Advise the patient to take the next prescribed dose at the usual time.

2.2 Dose Modification Guidelines

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

​ Recommended INLYTA dosage increases and reductions are provided in Table 1.

​ Over the course of treatment, patients who tolerate INLYTA for at least two consecutive weeks with no adverse reactions Grade >2 (according to the Common Toxicity Criteria for Adverse Events [CTCAE]), are normotensive, and are not receiving anti-hypertension medication, may have their dose increased.

Table 1:Recommended Dosage Increases and Reductions for INLYTA

​ Dose Modification	Dose Regimen
* for management of adverse drug reactions † from 5 mg twice daily
​ Recommended starting dosage	5 mg twice daily
​ Dosage increase
​ First dose increase	7 mg twice daily
​ Second dose increase	10 mg twice daily
​ Dosage reduction *
​ First dose reduction †	3 mg twice daily
​ Second dose reduction	2 mg twice daily

​ Recommended dosage modifications for adverse reactions for INLYTA are provided in Table 2.

Table 2:Recommended Dosage Modification for INLYTA for Adverse Reactions

​ Adverse Reaction	Severity	Dosage Modifications for INLYTA
​ Hypertension [see Warnings and Precautions (5.1) ]	SBP > 150 mmHg or DBP > 100 mmHg despite antihypertensive treatment	Reduce dose by one level.
	SBP > 160 mmHg or DBP > 105 mmHg	Withhold until BP < 150/100 mmHg. Resume at a reduced dose.
	Grade 4 or hypertensive crisis	Permanently discontinue.
​ Hemorrhage [see Warnings and Precautions (5.4) ]	Grade 3 or 4	Withhold until resolution to Grade 0 or 1 or baseline. Either resume at a reduced dose or discontinue depending on the severity and persistence of adverse reaction.
​ Cardiac failure [see Warnings and Precautions (5.5) ]	Asymptomatic cardiomyopathy (left ventricular ejection fraction greater than 20% but less than 50% below baseline or below the lower limit of normal if baseline was not obtained)	Withhold until resolution to Grade 0 or 1 or baseline. Resume at a reduced dose.
	Clinically manifested congestive heart failure	Permanently discontinue.
​ Impaired wound healing [see Warnings and Precautions (5.8) ]	Any Grade	The safety of resumption of INLYTA after resolution of wound healing has not been established. Either resume at a reduced dose or discontinue depending on the severity and persistence of the adverse reaction.
​ Reversible Posterior Leukoencephalopathy Syndrome [see Warnings and Precautions (5.9) ]	Any Grade	Permanently discontinue.
​ Proteinuria [see Warnings and Precautions (5.10) ]	2 or more grams proteinuria per 24 hours	Withhold until resolution to less than 2 grams per 24 hours. Resume at a reduced dose.
​ Other Adverse Reactions	Grade 3	Reduce dosage by one level.
	Grade 4	Withhold until resolution to Grade 2. Resume at a reduced dose.

​ Table 3 represents additional recommended dosage modifications for adverse reactions when INLYTA is administered in combination with avelumab or pembrolizumab.

​ See the Full Prescribing Information for additional dosage information for avelumab or pembrolizumab including dose modifications for immune-mediated adverse reactions.

Table 3: Recommended Dosage Modification for Adverse Reactions for INLYTA in Combination with Avelumab or Pembrolizumab

​ Treatment	Adverse Reaction	Severity *	Dosage Modifications for INLYTA
ALT = alanine aminotransferase, AST = aspartate aminotransferase, ULN = upper limit normal
* Based on Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. † Consider corticosteroid therapy ‡ If rechallenging with INLYTA, consider dosage reduction per Table 1. Consider rechallenge with a single drug or sequential rechallenge with both drugs after recovery.
​ INLYTA in combination with avelumab OR pembrolizumab	Liver enzyme elevations †	ALT or AST at least 3 times ULN but less than 10 times ULN without concurrent total bilirubin at least 2 times ULN	Withhold both INLYTA and avelumab or pembrolizumab until resolution to Grades 0–1 Consider rechallenge with INLYTA and/or avelumab or pembrolizumab ‡
		ALT or AST increases to more than 3 times ULN with concurrent total bilirubin at least 2 times ULN or ALT or AST at least 10 times ULN	Permanently discontinue both INLYTA and avelumab or pembrolizumab
	Diarrhea	Grade 1–2	Initiate symptomatic medications.
		Grade 3	Interrupt INLYTA and initiate symptomatic medications. If diarrhea is controlled, INLYTA may be resumed at either the same dose or reduced by 1 dose level.
		Grade 4	Withhold INLYTA until resolution to Grade <2, then restart INLYTA dose reduced by 1 dose level
​ INLYTA in combination with avelumab	Major Adverse Cardiovascular Events (MACE)	Grade 3 or 4	Permanently discontinue