June 26, 2016
Recommended Topic Related To:

Berinert

"The US Food and Drug Administration (FDA) today approved a drug for children and adults with hemophilia B called albutrepenonacog alfa (Idelvion, CSL Behring), which combines albumin with factor IX to reduce injection frequency.

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Berinert




Warnings
Precautions

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Hypersensitivity

Severe hypersensitivity reactions may occur. Epinephrine should be immediately available for treatment of acute severe hypersensitivity reaction [see PATIENT INFORMATION]. The signs and symptoms of hypersensitivity reactions may include hives, generalized urticaria, tightness of the chest, wheezing, hypotension, and/or anaphylaxis during or after injection of Berinert.

Because hypersensitivity reactions may have symptoms similar to HAE attacks, treatment methods should be carefully considered. In case of suspected hypersensitivity, immediately discontinue administration of Berinert and institute appropriate treatment.

Thromboembolic Events

Serious arterial and venous thromboembolic (TE) events have been reported at the recommended dose of C1 Esterase Inhibitor (Human) products, including Berinert, following administration in patients with HAE. Risk factors may include the presence of an indwelling venous catheter/access device, prior history of thrombosis, underlying atherosclerosis, use of oral contraceptives or certain androgens, morbid obesity, and immobility. Benefits of treatment of HAE attacks should be weighed against the risks of TE events in patients with underlying risk factors. Monitor patients with known risk factors for TE events during and after Berinert administration.

TE events have also been reported following administration of a C1 Esterase Inhibitor (Human) product when used for unapproved indications at higher than recommended doses1,2 [see OVERDOSAGE and Nonclinical Toxicology].

Transmission Of Infectious Agents

Because Berinert is made from human blood, it may contain infectious agents (eg, viruses and, theoretically, the Creutzfeldt-Jakob disease [CJD] agent) that can cause disease. The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by processes demonstrated to inactivate and/or remove certain viruses during manufacturing [see DESCRIPTION and PATIENT INFORMATION].

Despite these measures, such products may still potentially transmit disease. There is also the possibility that unknown infectious agents may be present in such products. Since 1979, a few suspected cases of viral transmission have been reported with the use of Berinert outside the US, including cases of acute hepatitis C. From the incomplete information available from these cases, it was not possible to determine with certainty if the infections were or were not related to prior administration of Berinert. With the introduction of the pasteurization step (heat treatment in aqueous solution at 60°C for 10 hours) in 1985, case reports on suspected transmission of viruses have not demonstrated a causal relationship to the administration of Berinert.

The physician should discuss the risks and benefits of this product with the patient before prescribing or administering it to the patient [see PATIENT INFORMATION]. All infections thought by a physician possibly to have been transmitted by Berinert should be reported by lot number, by the physician, or other healthcare provider to the CSL Behring Pharmacovigilance Department at 1-866-915-6958.

Laryngeal Attacks

Given the potential for airway obstruction during acute laryngeal HAE attacks, patients self-administering Berinert should be advised to immediately seek medical attention in an appropriate healthcare facility after treatment with Berinert.

Patient Counseling Information

See FDA-approved patient labeling (PATIENT INFORMATION).

Inform patients to immediately report the following to their physician:

  • Signs and symptoms of allergic hypersensitivity reactions, such as hives, urticaria, tightness of the chest, wheezing, hypotension and/or anaphylaxis experienced during or after injection of Berinert [see WARNINGS AND PRECAUTIONS]
  • Signs and symptoms of a thromboembolic event including pain and/or swelling of an arm or leg with warmth over the affected area, discoloration of an arm or leg, unexplained shortness of breath, chest pain or discomfort that worsens on deep breathing, unexplained rapid pulse, numbness or weakness on one side of the body. Advise patients with known risk factors for thromboembolic events that they are at an increased risk for these events [see WARNINGS AND PRECAUTIONS].
  • Advise female patients to notify their physician if they become pregnant or intend to become pregnant during the treatment of acute abdominal or facial attacks of HAE with Berinert.
  • Advise patients to notify their physician if they are breastfeeding or plan to breastfeed.
  • Advise patients to consult with their healthcare professional prior to travel.
  • Advise patients/caregivers to bring an adequate supply of Berinert when traveling.
  • Advise patients to bring Berinert with them when they visit a healthcare provider/ facility for an acute HAE attack.
  • Advise patients that, because Berinert is made from human blood, it may carry a risk of transmitting infectious agents, eg, viruses, and, theoretically, the Creutzfeldt- Jakob (CJD) agent [see WARNINGS AND PRECAUTIONS and DESCRIPTION]. Inform patients of the risks and benefits of Berinert before prescribing or administering it to the patient.

Self-administration — Ensure that the patient (or caregiver) is an appropriate candidate for self-administration, this includes, but not limited to a determination that:

  • The patient (or caregiver) is reliably able to recognize the signs and symptoms of their HAE attacks.
  • The patient (or caregiver) has the necessary dexterity and comprehension to be trained to self-administer.

If self-administration is deemed appropriate, ensure that the patient/caregiver receives clear instructions and training on intravenous administration in the home or other appropriate setting and has demonstrated the ability to perform intravenous infusions.

  • Ensure the patients/caregivers understand the importance of not starting selfadministration if the attack (regardless of type) has progressed to a point that the patient/caregiver would be unable to successfully prepare or administer Berinert.
  • Given the potential for airway obstruction during acute laryngeal HAE attacks, patients self-administering Berinert should be advised to immediately seek medical attention in an appropriate healthcare facility in addition to treatment with Berinert.
  • To help exclude the possibility that another potentially serious medical cause may be responsible for their symptoms, advise patients self-administering Berinert to contact their healthcare provider after treating suspected abdominal HAE attacks.
  • Instruct patients/caregivers to record the lot number from the Berinert vial label every time they use Berinert.

The attached BERINERT “Patient Product Information (PPI)” contains more detailed instructions for patients/caregivers who will be self-administering BERINERT.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

No animal studies have been completed to evaluate the effects of Berinert on carcinogenesis, mutagenesis, and impairment of fertility.

Use In Specific Populations

Pregnancy

Pregnancy Category C. Animal reproduction studies have not been conducted with Berinert. It is not known whether Berinert can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Berinert should be given to a pregnant woman only if clearly needed. In a retrospective case collection study, 20 pregnant women ranging in age from 20 to 35 years received Berinert with repeated doses up to 3,500 IU per attack; these women reported no complications during delivery and no harmful effects on their 34 neonates.

Labor And Delivery

The safety and effectiveness of Berinert administration prior to or during labor and delivery have not been established. Use only if clearly needed.

Nursing Mothers

It is not known whether Berinert is excreted in human milk. Because many drugs are excreted in human milk, use only if clearly needed when treating a nursing woman.

Pediatric Use

Safety and efficacy of Berinert in children (ages 0 through 12) have not been established. The clinical studies included an insufficient number of subjects in this age group to determine whether they respond differently from older subjects. In the pharmacokinetic study [see CLINICAL PHARMACOLOGY], the safety and pharmacokinetics of Berinert were evaluated in 5 children (ages 3 through 12) and in 8 adolescent subjects (ages 13 through 16). The 5 children less than 12 years had a shorter half-life (16.7 ± 5.8 hours) and faster clearance (1.9 ± 1.1 mL/hr/kg) compared to adults (half-life: 18.4 ± 3.5 hours, clearance 1.44 ± 0.67 mL/hr/kg).

Geriatric Use

Safety and efficacy of Berinert in the geriatric population have not been established. Clinical studies with Berinert included four subjects older than 65 years. The clinical studies included an insufficient number of subjects in this age group to determine whether they respond differently from younger subjects.

REFERENCES

1. German Medical Profession's Drugs Committee. Severe thrombus formation of Berinert® HS. Deutsches Ärzteblatt. 2000;97:B-864.

2. Horstick, G et al. Application of C1-Esterase Inhibitor During Reperfusion of Ischemic Myocardium: Dose-Related Beneficial Versus Detrimental Effects. Circulation. 2001;104:3125-3131.

This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 6/16/2016

Warnings
Precautions

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


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