Hespan

Black Box Warnings

Do not use in critically ill adult patients including those with sepsis, and those admitted to the ICU

Avoid use in patients with pre-existing renal dysfunction

Discontinue use at the first sign of renal injury

Need for renal replacement therapy has been reported up to 90 days after administration; continue to monitor renal function for at least 90 days in all patients

Avoid use in patients undergoing open heart surgery in association with cardiopulmonary bypass due to excess bleeding

Discontinue at the first sign of coagulopathy

Contraindications

Hypersensitivity to hetastarch

Severe bleeding disorders, severe CHF, severe renal failure

Cautions

Allergy to corn, liver disease, renal impairment, thrombocytopenia

Risk of pulmonary edema or CHF

Potential for circulatory overload

Hetastarch in lactated solution contains potassium & sodium

Hextend not to be used in leukapheresis or lactic acidosis

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Tell your caregivers right away if you have:

• wheezing or gasping for breath, rapid breathing, sweating, and anxiety;
• a light-headed feeling, like you might pass out;
• weak pulse, slow breathing;
• chest pain, fever, chills, cough; or
• easy bruising, unusual bleeding, or any bleeding that will not stop.

Rare but serious side effects may include:

• severe headache, vision or speech problems, mental changes;
• drooping eyelids, loss of feeling in your face, tremors, trouble swallowing; or
• severe skin reaction -- fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Hetastarch can harm your kidneys. Call your doctor at once if you have any of these symptoms of kidney damage: swelling, rapid weight gain, unusual tiredness, nausea, vomiting, feeling short of breath, red or pink urine, painful or difficult urination, or little or no urinating.

Common side effects may include:

• mild itching or skin rash;
• mild headache;
• muscle pain; or
• swollen glands, mild flu symptoms.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

You should not receive this medication if you are allergic to hetastarch, or if you have:

• a bleeding or blood clotting disorder;

• kidney disease;

• congestive heart failure; or

• urination problems not caused by hypovolemia (decreased blood plasma volume).

If possible before you receive hetastarch, tell your doctor if you have:

• liver disease;

• a history of heart disease; or

• if you are allergic to corn.

FDA pregnancy category C. It is not known whether hetastarch will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

It is not known whether hetastarch passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

In an emergency situation it may not be possible to tell your caregivers about your health conditions, or if you are pregnant or breast-feeding. Make sure any doctor caring for your pregnancy or your baby knows you have received this medicine.

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.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• 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.

This information should not be used to decide whether or not to take Hespan or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Hespan. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

 Single-use container:

• 30 g hetastarch in 500 mL of 0.9% sodium chloride injection.

The serious adverse events reported in clinical trials are increased mortality and renal replacement therapy renal in critically ill patients.

Most common adverse reactions are hypersensitivity, coagulopathy, hemodilution, circulatory overload and metabolic acidosis.

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Three randomized controlled trials (RCTs) followed critically ill adult patients treated with different HES products for 90 days.

One trial (N=804) in severe sepsis patients using HES product (not approved in the U.S.) reported increased mortality (relative risk, 1.17; 95% CI, 1.01 to 1.36; p=0.03) and RRT (relative risk, 1.35; 95% CI, 1.01 to 1.80; p=0.04) in the HES treatment arm.4

Another trial (N=196) using different HES in severe sepsis patients reported no difference in mortality (relative risk,1.20; 95% CI, 0.83 to 1.74; p=0.33) and a trend for RRT (relative risk, 1.83; 95% CI, 0.93 to 3.59; p=0.06) in HES patients.5

A third trial (N=7000) using different HES in a heterogeneous patient population consisting of critically ill adult patients admitted to the ICU reported no difference in mortality (relative risk, 1.06; 95% CI, 0.96 to 1.18; p=0.26) but increased use of RRT (relative risk, 1.21; 95% CI, 1.00 to 1.45; p=0.04) in HES patients.6

Postmarketing Experience

Because adverse reactions are reported voluntarily post-approval from a population of uncertain size, it is not always possible to reliably estimate the frequency of these reactions or establish a causal relationship to product exposure.

The following adverse reactions have been identified and reported during the post-approval use of HES products:

need for renal replacement therapy

including death, life-threatening anaphylactic/anaphylactoid reactions, cardiac arrest, ventricular fibrillation, severe hypotension, non-cardiac pulmonary edema, laryngeal edema, bronchospasm, angioedema, wheezing, restlessness, tachypnea, stridor, fever, chest pain, bradycardia, tachycardia, shortness of breath, chills, urticaria, pruritus, facial and periorbital edema, coughing, sneezing, flushing, erythema multiforme, and rash [see Warnings and Precautions (5.3)].

including circulatory overload, congestive heart failure, and pulmonary edema [see Warnings and Precautions (5.4)].

including intracranial bleeding, bleeding and/or anemia due to hemodilution [see Warnings and Precautions (5.4)] and/or Factor Vlll deficiency, acquired von Willebrand’s-like syndrome, and coagulopathy including rare cases of disseminated intravascular coagulopathy and hemolysis.

including metabolic acidosis.

including vomiting, peripheral edema of the lower extremities, submaxillary and parotid glandular enlargement, mild influenza-like symptoms, headaches, and muscle pains. Hydroxyethyl starch-associated pruritus has been reported in some patients with deposits of hydroxyethyl starch in peripheral nerves.

Hespan® (6% hetastarch in 0.9% sodium chloride injection) is supplied sterile and nonpyrogenic in 500 mL EXCEL® Containers packaged 12 per case.

NDC                        REF                          Volume
0264-1965-10         L6511                       500 mL

Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. Protect from freezing.

Store at room temperature (25°C); however, brief exposure up to 40°C does not adversely affect the product.

Storage in automated dispensing machines: Brief exposure up to 2 weeks to ultraviolet or fluorescent light does not adversely affect the product labeling legibility; prolonged exposure can cause fading of the red label. Rotate stock frequently.

Rx only

EXCEL and Hespan are registered trademarks of B. Braun Medical Inc.

B. Braun Medical Inc.
Bethlehem, PA 18018-3524 USA
1-800-227-2862
www.bbraun.com

Y36-002-894  LD-233-3

Applies to hetastarch: parenteral injection

Side effects include:

Hypersensitivity reactions, coagulopathy, hemodilution, circulatory overload, metabolic acidosis, CHF, pulmonary edema, bleeding, vomiting, peripheral edema, submaxillary and parotid glandular enlargement, mild influenza-like symptoms, headache, muscle pain.

Included as part of the "PRECAUTIONS" Section