Drug Safety-related Labeling Changes (SrLC)

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HEPARIN SODIUM IN PLASTIC CONTAINER (NDA-017029)

(HEPARIN SODIUM)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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11/16/2018 (SUPPL-141)

Approved Drug Label (PDF)

4 Contraindications

(addition underlined)

  • An uncontrolled active bleeding state

5 Warnings and Precautions

5.1 Fatal Medication Errors

(additions underlined)

Do not use Heparin Sodium Injection as a “catheter lock flush” product. Heparin Sodium Injection is supplied in syringes containing a highly concentrated solution of 10,000 units in 1 mL (5,000 units per 0.5 mL). Fatal hemorrhages have occurred in pediatric patients due to medication errors in which 1 mL Heparin Sodium Injection vials were confused with 1 mL “catheter lock flush” vials. Carefully examine all Heparin Sodium Injection syringes to confirm the correct syringe choice prior to administration of the drug.

5.2 Hemorrhage

(additions underlined)

Avoid using heparin in the presence of major bleeding, except when the benefits of heparin therapy outweigh the potential risks.

Hemorrhage can occur at virtually any site in patients receiving heparin. Fatal hemorrhages have occurred. Adrenal hemorrhage (with resultant acute adrenal insufficiency), ovarian hemorrhage, and retroperitoneal hemorrhage have occurred during anticoagulant therapy   with heparin. A higher incidence of bleeding has been reported in patients, particularly women, over 60 years of age. An unexplained fall in hematocrit, fall in blood pressure or any other unexplained symptom should lead to serious consideration of a hemorrhagic event.

5.5 Coagulation Testing and Monitoring

(additions underlined)

When using a full dose heparin regimen, adjust the heparin dose based on frequent blood coagulation tests. If the coagulation test is unduly prolonged or if hemorrhage occurs, discontinue heparin promptly.  Periodic platelet counts and hematocrits are recommended during the entire course of heparin therapy, regardless of the route of administration.

6 Adverse Reactions

6.1 Postmarketing Experience

(additions underlined)

The following adverse reactions have been identified during post approval use of Heparin Sodium Injection. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

...

  • Local Irritation Local irritation, erythema, mild pain, hematoma or ulceration may follow deep subcutaneous (intrafat) injection of heparin sodium. Because these complications are much more common after intramuscular use, the intramuscular route is not recommended.

  • Histamine-like reactions – Such reactions have been observed at the site of injections. Necrosis of the skin has been reported at the site of subcutaneous injection of heparin, occasionally requiring skin grafting.

8 Use in Specific Populations

8.1 Pregnancy

(additions underlined)

If available, preservative-free Heparin Sodium Injection is recommended when heparin therapy is needed during pregnancy.

8.4 Pediatric Use

(subsection revised, additions underlined)

Pediatric dosing is not achievable with the prefilled syringe presentation. Use another heparin product presentation when dosing pediatric patients.

8.5 Geriatric Use

(additions underlined)

There are limited adequate and well-controlled studies in patients 65 years and older, however, a higher incidence of bleeding has been reported in patients, particularly women, over 60 years of age.Patients over 60 years of age may require lower doses of heparin. Lower doses of heparin may be indicated in these patients.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

(additions underlined)

Hypersensitivity

Inform patients that generalized hypersensitivity reactions have been reported. Necrosis of the skin has been reported at the site of subcutaneous injection of heparin.

08/24/2017 (SUPPL-140)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

(PLLR conversion)

Risk Summary

There are no available data on heparin sodium use in pregnant women to inform a drug- associated risk of major birth defects and miscarriage. In published reports, heparin exposure during pregnancy did not show evidence of an increased risk of adverse maternal or fetal outcomes in humans. No teratogenicity, but early embryo-fetal death was observed in animal reproduction studies with administration of heparin sodium to pregnant rats and rabbits during organogenesis at doses approximately 10 times the maximum recommended human dose (MRHD) of 40,000 units/24 hours infusion (see Data). Consider the benefits and risks of Heparin Sodium in 0.45% Sodium Chloride Injection or Heparin Sodium in 5% Dextrose Injection to a pregnant woman and possible risks to the fetus when prescribing Heparin Sodium in 0.45% Sodium Chloride Injection or Heparin Sodium in 5% Dextrose Injection to a pregnant woman.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Human Data

The maternal and fetal outcomes associated with uses of heparin via various dosing methods and administration routes during pregnancy have been investigated in numerous studies. These studies generally reported normal deliveries with no maternal or fetal bleeding and no other complications.

Animal Data

In a published study conducted in rats and rabbits, pregnant animals received heparin intravenously during organogenesis at a dose of 10,000 USP units/kg/day, approximately 10 times the maximum human daily dose based on body weight. The number of early resorptions increased in both species. There was no evidence of teratogenic effects.

8.2 Lactation

(PLLR conversion)

Risk Summary

There is no information regarding the presence of Heparin Sodium in 0.45% Sodium Chloride Injection or Heparin Sodium in 5% Dextrose Injection in human milk, the effects on the breastfed infant, or the effects on milk production. Due to its large molecular weight, heparin is not     likely to be excreted in human milk, and any heparin in milk would not be orally absorbed by     a nursing infant. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Heparin Sodium in 0.45% Sodium Chloride Injection or Heparin Sodium in 5% Dextrose Injection and any potential adverse effects on the breastfed infant from Heparin Sodium in 0.45% Sodium Chloride Injection or Heparin Sodium in 5% Dextrose Injection or from the underlying maternal condition.

Other

PLR conversion, please refer to label

Questions related to the drug data in these files should be directed to the Center for Drug Evaluation and Research, Division of Drug Information
druginfo@fda.hhs.gov.

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