Proleukin

PROLEUKIN- aldesleukin injection, powder, lyophilized, for solution
Clinigen Limited

WARNING: CAPILLARY LEAK SYNDROME (CLS), NEUROLOGIC TOXICITIES and SERIOUS INFECTIONS

  • Capillary leak syndrome (CLS), including life threatening or fatal reactions, has occurred in patients treated with Proleukin. Do not administer Proleukin to patients with significant cardiac, pulmonary, renal, and hepatic impairment. Administer Proleukin in a hospital setting with an intensive care facility. Withhold or discontinue Proleukin as recommended [see Dosage and Administration (2.4), Contraindications (4), Warnings and Precautions (5.1)].
  • Neurologic toxicities, which may be life-threatening or result in coma or permanent neurological deficits, have occurred in patients treated with Proleukin. Withhold or discontinue Proleukin as recommended [see Dosage and Administration (2.4), Warnings and Precautions (5.2)].
  • Serious Infections including sepsis and bacterial endocarditis have occurred in patients treated with Proleukin. Treat pre-existing bacterial infections prior to initiation of Proleukin therapy and withhold Proleukin as recommended [see Dosage and Administration (2.4), Warnings and Precautions (5.3)].

1 INDICATIONS AND USAGE

1.1 Metastatic Renal Cell Carcinoma

Proleukin is indicated for the treatment of adults with metastatic renal cell carcinoma (RCC).

1.2 Metastatic Melanoma

Proleukin is indicated for the treatment of adults with metastatic melanoma.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Evaluation and Testing Before Initiating Proleukin

Conduct baseline hematologic, chemistry, renal and hepatic function tests. Additionally, evaluate cardiac ejection fraction, coronary artery disease as appropriate, pulmonary function with PFTs, and evaluate for renal, hepatic, and CNS impairment prior to initiating treatment with Proleukin [see Contraindications (4), Warnings and Precautions (5.1, 5.2)].

Verify pregnancy status of females of reproductive potential prior to initiating Proleukin [see Warnings and Precautions (5.6), Use in Specific Populations (8.1, 8.3)].

2.2 Recommended Dosage

Administer Proleukin in an inpatient hospital setting. An intensive care facility with specialists skilled in cardiopulmonary or intensive care medicine must be available [see Warnings and Precautions (5.1)].

The recommended dosage of Proleukin for metastatic renal cell carcinoma and metastatic melanoma is described in Table 1.

Administer Proleukin as an intravenous infusion after dilution [see Dosage and Administration (2.5)].

Administer pre-infusion medications and supportive treatment, as appropriate, prior to and during each infusion [see Dosage and Administration (2.3)]. Discontinue Proleukin for unacceptable toxicity [see Dosage and Administration (2.4)].

Table 1: Recommended Dosage of Proleukin

1 A maximum of 28 doses (2 cycles) per treatment course

Each course of therapy consists of the following:

Cycle 1

Days 1-5

600,000 IU/kg (0.037 mg/kg) every 8 hours; maximum of 14 doses1

Rest period

Days 6-14

Cycle 2

Days 15-19

600,000 IU/kg (0.037 mg/kg) every 8 hours; maximum of 14 doses1

Evaluate patients for response approximately 4 weeks after completion of a course of therapy and again immediately prior to the scheduled start of the next treatment course.

Additional courses of treatment may be administered to patients if there is a treatment response following the last course, and the patient did not experience any adverse reactions in previous course(s) that led to permanent discontinuation [see Dosage and Administration (2.4)].

Separate each treatment course by a rest period of at least 7 weeks from the date of hospital discharge.

2.3 Premedication and Supportive Medications

Premedicate patients with an antipyretic immediately prior to beginning Proleukin. Continue antipyretics during treatment as needed for fever [see Warnings and Precautions (5.1, 5.10)].

Administer prophylactic antibiotics per institutional guidelines prior to beginning Proleukin and throughout the treatment course for patients with indwelling central catheters [see Warnings and Precautions (5.3)].

Administer prophylactic medication for gastrointestinal irritation and bleeding during each Proleukin treatment course [see Adverse Reactions (6.1)].

Additional medications may be needed if patients experience hypotension, dyspnea, rigors, nausea, diarrhea, pruritis, or dermatitis [see Warnings and Precautions (5.1, 5.8, 5.9)].

2.4 Dosage Modifications for Adverse Reactions

No dose reduction for Proleukin is recommended for adverse reactions. In general, withhold or interrupt a dose or permanently discontinue Proleukin based on the severity of the adverse reaction as described in Table 2.

Table 2: Recommended Dosage Modifications for Adverse Reactions

Adverse Reaction

Severity

Dosage Modification

Cardiovascular [see Warnings and Precautions (5.1)]

  • Atrial fibrillation,
  • Supraventricular tachycardia, or
  • Bradycardia that requires treatment or is recurrent or persistent
  • Decrease in systolic blood pressure to <90 mmHg

Withhold until patient is asymptomatic with full recovery to normal sinus rhythm

  • Sustained ventricular tachycardia (≥5 beats)
  • Cardiac rhythm disturbances not controlled or unresponsive to management
  • ECG changes consistent with ischemia or myocardial infarction or angina/chest pain
  • Cardiac tamponade

Permanently discontinue

Respiratory

[see Warnings and Precautions (5.1)]

  • O2 saturation <90%

Withhold until O2 saturation is >90%

  • Intubation for >72 hours

Permanently discontinue

Neurologic

[see Warnings and Precautions (5.2)]

  • Mental status changes, including moderate confusion or agitation

Withhold until completely resolved

  • Coma or toxic psychosis lasting >48 hours
  • Repetitive or difficult to control seizures

Permanently discontinue

Gastrointestinal [see Warnings and Precautions (5.1)]

Fecal immunochemical test (FIT) or fecal occult blood test (FOBT) positive

Withhold until FIT or FOBT negative

Bowel ischemia/perforation or GI bleeding requiring surgery

Permanently discontinue

Hepatic [see Warnings and Precautions (5.1)]

Signs of hepatic toxicity including liver pain or ≥ Grade 3 AST or ALT elevation

Withhold all further treatment for that course. Initiate a new course of treatment no sooner than 7 weeks after signs of hepatic toxicity have resolved and hospital discharge

Hepatic failure

Permanently discontinue

Dermatologic [see Warnings and Precautions (5.5, 5.7)]

Bullous dermatitis or marked worsening of pre-existing skin condition

Withhold until all signs of bullous dermatitis have resolved

Infectious

[see Warnings and Precautions (5.3)]

Sepsis syndrome, patient is clinically unstable

Withhold until sepsis syndrome has resolved, patient is clinically stable, infection is under treatment

Renal

[see Warnings and Precautions (5.1, 5.4)]

Serum creatinine >4.5 mg/dL or a serum creatinine of ≥4 mg/dL in the presence of severe volume overload, acidosis, or hyperkalemia

Withhold until serum creatinine levels return to normal (<1.5 mg/dL) or baseline and fluid and electrolyte status are stable

Persistent oliguria, urine output of <10 mL/hr for 16-24 hours with rising SCr

Withhold until urine output >10 mL/hour with a decrease of serum creatinine >1.5 mg/dL or normalization of serum creatinine

Renal failure requiring dialysis >72 hours

Permanently discontinue

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