Unituxin® (dinutuximab) Injection | United Therapeutics

Important Safety Information

Contraindications

Patients who are allergic to dinutuximab should not take Unituxin.

Warnings and Precautions

Serious Infusion Reactions

• In a clinical study, 35 (26%) patients taking Unituxin experienced severe (Grade 3 or infusion reactions. Serious infusion reactions included swelling of the face and upper airway, difficult or abnormal breathing, bronchospasm, rash and hives, and low blood pressure. Urgent intervention included blood pressure support, bronchodilator therapy, corticosteroids, infusion rate reduction, infusion interruption, or permanent discontinuation of Unituxin.
• Infusion reactions generally happen during or within 24 hours after treatment with Unituxin. Tell your healthcare professional right away if you notice any signs or symptoms of serious infusion reactions, including facial or lip swelling, rash, difficulty breathing, lightheadedness, or dizziness, that occur during or within 24 hours following infusion. Your healthcare professional will decide whether treatment should be stopped temporarily or permanently.

Neurotoxicity

• Pain:
  • Your healthcare professional will administer medication before, during, and after treatment to help manage pain. Tell your healthcare professional right away about any severe or worsening pain.
  • In a clinical study, 114 (85%) patients taking Unituxin experienced pain despite pretreatment with pain medicine including morphine sulfate infusion. Severe (Grade 3) pain occurred in 68 (51%) patients taking Unituxin compared to 5 (5%)patients who were not taking Unituxin. Pain typically occurred during the Unituxin infusion and was most commonly reported as stomach pain, generalized pain, pain in the arms or legs, back pain, nerve pain, muscle and bone pain of the chest, and joint pain.
  • If severe pain is experienced, your healthcare professional may reduce the speed at which Unituxin is given. Unituxin may be stopped if pain is not adequately controlled through medical intervention.
• Peripheral Neuropathy:
  • Symptoms of neuropathy (may include numbness, tingling, burning), or weakness.Report any signs or symptoms of neuropathy immediately to your healthcare provider.
  • In a clinical study, severe (Grade 3) peripheral sensory neuropathy occurred in 2 (1%) patients and severe peripheral motor neuropathy occurred in 2 (1%) patients taking Unituxin compared to zero patients who were not taking Unituxin.
  • Treatment with Unituxin may need to be permanently discontinued in patients with Grade 2 peripheral motor neuropathy, Grade 3 sensory neuropathy that interferes with daily activities for more than 2 weeks, or Grade 4 sensory neuropathy.
• Neurological Disorders of the Eye:
  • Neurological disorders of the eye can be serious. Tell your healthcare professional immediately if you experience blurred vision, sensitivity to light, drooping of the upper eyelid, double vision, optic disc swelling, or fixed or unequal pupil size as these can be signs and symptoms of a neurological disorder of the eye. Patients who experience neurological disorders of the eye may need to have the Unituxin dose reduced or permanently stopped.
  • In clinical studies, neurological disorders of the eye experienced by 2 or more patients treated with Unituxin included blurred vision, sensitivity to light, dilated pupils, an inability to move the eyelid, fixed or unequal pupils, optic nerve disorder, drooping of the eyelid, and swelling.
• Prolonged Urinary Retention:
  • Urinary retention (inability to completely empty the bladder) that persists for weeks to months after stopping opioids has occurred in patients treated with Unituxin. Report to your healthcare provider persistent urinary retention that does not resolve after having stopped opioid therapy. If you experience prolonged urinary retention, your healthcare professional will decide whether treatment should be stopped.
• Transverse Myelitis:
  • Transverse myelitis has occurred in patients treated with Unituxin. Symptoms may include weakness, tingling or burning sensation, reduced sensation, or inability to control urine. Report signs or symptoms of transverse myelitis immediately to your healthcare provider. Your healthcare professional will determine if you have transverse myelitis and stop treatment as necessary.
• Reversible Posterior Leukoencephalopathy Syndrome (RPLS):
  • RPLS is swelling in the back part of the brain. It has occurred in patients treated with Unituxin. Symptoms may include severe headache, high blood pressure, change in vision, feeling drowsy or tired, or seizures (fits). Report signs or symptoms immediately to your healthcare provider. Unituxin may be stopped in patients with signs and symptoms of RPLS.

Capillary Leak Syndrome

• Capillary leak syndrome is a potentially life-threatening condition in which fluid and proteins leak out of tiny blood vessels and flow into surrounding tissue. This leads to dangerously low blood pressure. If severe capillary leak syndrome is experienced, the speed at which Unituxin is given may need to be interrupted, reduced, or permanently stopped.
• Signs and symptoms of capillary leak syndrome include swelling of the arms, legs, and other parts of the body; shock; lightheadedness; weakness; fatigue; nausea; and rapid drop in blood pressure. Immediately report any signs or symptoms of capillary leak syndrome to your healthcare professional.
• In a clinical study, severe (Grades 3 to 5) capillary leak syndrome occurred in 31 (23%) patients taking Unituxin and in no patients who were not taking Unituxin.

Low Blood Pressure

• In a clinical study, 22 (16%) patients taking Unituxin experienced severe (Grade 3 or 4) low blood pressure. Fluids will be given by your healthcare professional prior to treatment with Unituxin. Blood pressure should be watched closely during Unituxin treatment. Tell your healthcare professional right away if you experience any changes in breathing, dizziness or lightheadedness, fainting, or dehydration (symptoms may include unusual thirst, urinating less often than usual, dark colored urine, dry skin, or tiredness). Patients who get low blood pressure may need to have the speed at which Unituxin is given reduced or permanently stopped.

Infection

• In a clinical study, 17 (13%) patients experienced severe (Grade 3 or 4) bacteremia that required urgent intervention, and 24 (18%) patients experienced sepsis. Closely monitor for signs and symptoms of systemic infection such as fever or tiredness. Tell your healthcare professional if you notice any signs of an infection.
• Patients who develop systemic infection will need to temporarily stop treatment with Unituxin until the infection resolves.

Bone Marrow Suppression

• Patients taking Unituxin may have slow blood clotting. This is due to a lowering of the number of platelets in the blood. Unituxin may also cause low red blood cell count (anemia) and low white blood cell count. This may make patients more likely to develop an infection.
• In a clinical study, severe (Grade 3 or 4) platelet deficiency (39% vs. 25%), low red blood cell count (34% vs. 16%), low white blood cell count (34% vs. 13%), and fever along with a low white blood cell count (4% vs. 0 patients) occurred more commonly in patients who were taking Unituxin than in patients who were not taking Unituxin.

Electrolyte Abnormalities

• In a clinical study, electrolyte abnormalities occurring in at least 25% of patients who received Unituxin included low levels of sodium, low levels of potassium, and low levels of calcium in the bloodstream. Your healthcare professional will monitor these levels. Tell your healthcare professional about any seizures; a feeling that the heart is beating too hard or too fast, skipping a beat, or fluttering; or muscle cramping.

Atypical Hemolytic Uremic Syndrome

• Patients taking Unituxin may experience kidney problems, electrolyte abnormalities, low red blood cell count, or high blood pressure. Patients who experience these side effects may need to permanently stop treatment with Unituxin. Tell your healthcare professional about any fatigue, dizziness, fainting, extreme skin paleness, swelling, less urine output than normal, or blood in the urine.

Tell your healthcare professional if you are pregnant before taking Unituxin.

• Unituxin may cause harm to an unborn child. Women who are taking Unituxin should use effective birth control measures during treatment and for 2 months after the last dose of Unituxin.

Common Serious Adverse Reactions

The following is a list of the most common serious adverse reactions seen in 5% or more of patients taking Unituxin:

• Infections
• Infusion reactions
• Low levels of potassium in the blood
• Low blood pressure
• Pain
• Fever
• Capillary leak syndrome (a potentially life-threatening condition in which fluid and proteins leak out of tiny blood vessels and flow into surrounding tissue, leading to dangerously low blood pressure)

Common Adverse Reactions

The following is a list of the most common adverse reactions seen in 25% or more of patients taking Unituxin:

• Pain
• Fever
• Slow blood clotting
• Reduced ability to fight infections (low levels of white blood cells of various kinds)
• Infusion reactions
• Low blood pressure
• Low levels of sodium in the blood
• Increased levels of the enzyme alanine aminotransferase in the blood
• Low red blood cell count
• Vomiting
• Diarrhea
• Low levels of potassium in the blood
• Capillary leak syndrome
• Hives
• Low levels of albumin in the blood
• Increased levels of the enzyme aspartate aminotransferase
• Low levels of calcium in the blood

The following side effects have also been observed in patients taking Unituxin after approval: prolonged urinary retention (inability to completely empty the bladder), transverse myelitis, and reversible posterior leukoencephalopathy (swelling in the back part of the brain).

Tell your healthcare professional about any side effect seen during treatment with Unituxin. These are not all the possible side effects of Unituxin. For more information, talk to your healthcare professional.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

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Please see Full Prescribing Information, including Boxed WARNING, for Unituxin.