IdaruCIZUMAB

Contraindications

None

Cautions

Patients treated with dabigatran have underlying disease states that predispose them to thromboembolic events; reversing dabigatran therapy exposes patients to the thrombotic risk of their underlying disease; to reduce this risk, resume anticoagulant therapy as soon as medically appropriate

There is insufficient clinical experience to evaluate risk of hypersensitivity to idarucizumab; discontinue if a serious hypersensitivity reaction occurs

Caution with hereditary fructose intolerance; the recommended dose of idarucizumab contains 4 g sorbitol as an excipient; when prescribing to patients with hereditary fructose intolerance, consider the combined daily metabolic load of sorbitol/fructose from all sources; administration of sorbitol in these patients is known to cause serious adverse reactions, including fatal reactions including hypoglycemia, hypophosphatemia, metabolic acidosis, increase in uric acid, and acute liver failure with breakdown of excretory and synthetic function

Re-elevation of coagulation parameters

• In a limited number of patients in the clinical program, between 12-24 hr after administrating idarucizumab 5 g, elevated coagulation parameters (eg, aPTT, ECT) have been observed
• If reappearance of clinically relevant bleeding together with elevated coagulation parameters is observed after administering idarucizumab 5 g, administration of an additional 5 g dose may be considered
• Similarly, patients who require a second emergency surgery/urgent procedure and have elevated coagulation parameters may receive an additional 5-g dose
• The safety and effectiveness of repeat treatment with idarucizumab have not been established

• The recommended dose of idarucizumab is 5 g (2 vials) given as two 2.5 mg intravenous infusions or two injections.
• An additional 5 g may be considered for patients who continue to bleed.

Tell your doctor if you are pregnant or plan to become pregnant.

There are no adequate and well-controlled studies of idarucizumab in animals or in pregnant women. It is also not known if idarucizumab can cause harm to the fetus. Idarucizumab should be given to a pregnant woman only if clearly needed. 

If idarucizumab is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

In an emergency situation it may not be possible to tell your caregivers about your health conditions. Make sure any doctor caring for you afterward knows you have received this medicine.

Contraindications

• Manufacturer states none.1

Warnings/Precautions

Thromboembolic Complications

Patients receiving therapy with dabigatran usually have underlying conditions that predispose them to thromboembolism; reversal of anticoagulation by idarucizumab exposes patients to their underlying thrombotic risk.1 12 Consider resumption of anticoagulant therapy as soon as medically appropriate.1

Hereditary Fructose Intolerance

Recommended 5-g dose of idarucizumab contains 4 g of sorbitol as an excipient.1

Serious adverse reactions, including death, reported in patients with hereditary fructose intolerance who received parenteral sorbitol.1 Minimum amount of sorbitol at which serious adverse reactions may occur in such patients not known.1

Immunogenicity

Potential for immunogenicity with use of all therapeutic proteins, including idarucizumab.1 16 Preexisting antibodies with cross-reactivity to idarucizumab detected in some patients in clinical trials; however, clinically important effects not observed.1 5 7

Sensitivity Reactions

Additional clinical experience needed to fully determine immunogenic risk.1 Adverse events possibly indicative of hypersensitivity reactions (e.g., pyrexia, bronchospasm, rash, pruritus) reported.1

Weigh anticipated benefits of idarucizumab against risk of hypersensitivity in patients with known hypersensitivity (e.g., anaphylactoid reaction) to idarucizumab or other ingredients in formulation.1 Discontinue idarucizumab and initiate appropriate therapy if severe hypersensitivity reaction occurs.1

Specific Populations

No adequate and well-controlled studies of idarucizumab in pregnant women.1 13 Animal reproductive and developmental studies with idarucizumab lacking.1 Use during pregnancy only when clearly needed.1 Safety and efficacy of idarucizumab during labor and delivery not established.1

Not known whether idarucizumab is distributed into human milk.1 Use with caution.1

Safety and efficacy not established.1 12

No overall differences in efficacy or safety between geriatric and younger patients; however, increased sensitivity of some older individuals cannot be ruled out.1 12

Does not affect dabigatran anticoagulation reversal effect of idarucizumab.1 13

Pharmacokinetic data lacking.1 13

Common Adverse Effects

Headache,1 hypokalemia,1 14 delirium,1 14 constipation,1 14 pyrexia.1 14

Specific Drugs

Importance of informing patients of signs and symptoms of allergic hypersensitivity reactions (e.g., anaphylaxis) that may occur during or after injection of idarucizumab.1

Importance of informing patients that reversing dabigatran therapy exposes them to thromboembolic risk of their underlying disease.1 Clinicians should consider resuming anticoagulant therapy as soon as the patient is sufficiently stable.1

Importance of advising patients to seek immediate medical attention for any signs or symptoms of bleeding.1

Importance of informing patients with hereditary fructose intolerance that idarucizumab solution for injection contains sorbitol.1 Importance of informing patients that parenteral sorbitol in patients with hereditary fructose intolerance associated with reports of hypoglycemia, metabolic acidosis, increase in uric acid, acute liver failure with breakdown of hepatic excretory and synthetic function, and death; such effects may occur during or after injection of idarucizumab.1

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

Importance of informing patients of other important precautionary information. (See Cautions.)

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

No dosage adjustment necessary; renal impairment does not impact the reversal effect of idarucizumab.

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache or constipation. Have patient report immediately to prescriber signs of blood clots (numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; angina; shortness of breath; fast heartbeat; or coughing up blood), signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), bleeding, confusion, shortness of breath, cough, or fast breathing (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience,and judgment in diagnosing, treating, and advising patients.

Applies to idarucizumab: intravenous solution

Along with its needed effects, idarucizumab may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking idarucizumab:

• Anxiety
• blurred vision
• bone pain
• chills
• cold sweats
• coma
• confusion
• convulsions
• cool, pale skin
• cough
• dark-colored urine
• deep or fast breathing with dizziness
• depression
• difficulty with breathing
• difficulty with swallowing
• dizziness
• drowsiness
• fast heartbeat
• fever
• general feeling of tiredness or weakness
• headache
• hives, itching, or skin rash
• increased hunger
• light-colored stools
• loss of appetite
• muscle tremors
• nausea
• nervousness
• nightmares
• numbness of the feet, hands, and around the mouth
• pain in the chest, groin, or legs, especially the calves
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• rapid, deep breathing
• restlessness
• seizures
• severe, sudden headache
• shakiness
• slurred speech
• stomach cramps
• stomach pain, continuing
• sudden loss of coordination
• sudden, severe weakness or numbness in the arm or leg
• sudden, unexplained shortness of breath
• tightness in the chest
• unusual tiredness or weakness
• vision changes
• vomiting
• yellow eyes or skin