PROLASTIN-C

PROLASTIN-C — alpha-1-proteinase inhibitor human
TALECRIS BIOTHERAPEUTICS, INC.

primary-displayVial Label

1 INDICATIONS AND USAGE

PROLASTIN-C is a preparation of alpha1 -proteinase inhibitor that is indicated for chronic augmentation and maintenance therapy in adults with emphysema due to deficiency of alpha1 -proteinase inhibitor (Alpha1 -PI, alpha1 -antitrypsin deficiency). The effect of augmentation therapy with any Alpha1 -PI product on pulmonary exacerbations and on the progression of emphysema in alpha1 -antitrypsin deficiency has not been demonstrated in adequately powered, randomized, controlled, clinical trials. PROLASTIN-C is not indicated as therapy for lung disease in patients in whom severe Alpha1 -PI deficiency has not been established.

2 DOSAGE AND ADMINISTRATION

For intravenous use only.

The recommended dose of PROLASTIN-C is 60 mg/kg body weight administered once weekly. Dose ranging studies using efficacy endpoints have not been performed with any alpha1 -proteinase inhibitor product. Each vial of PROLASTIN-C contains the labeled amount of functionally active Alpha1 -PI in milligrams (as determined by the capacity to neutralize porcine pancreatic elastase) as stated on the label.

PROLASTIN-C should be given intravenously at a rate of approximately 0.08 mL/kg/min as determined by the response and comfort of the patient. The recommended dosage of 60 mg/kg takes approximately 15 minutes to infuse.

2.1 Preparation and Handling

  • Do not freeze. Breakage of the diluent bottle may occur.
  • PROLASTIN-C and diluent should be at room temperature before reconstitution.
  • Inspect reconstituted PROLASTIN-C visually for particulate matter and discoloration prior to pooling and use.
  • PROLASTIN-C should be kept at room temperature after reconstitution and should be administered within 3 hours.
  • PROLASTIN-C should be given alone, without mixing with other agents or diluting solutions.
  • Reconstituted product from several vials may be pooled into an empty, sterile IV solution container by using aseptic technique.
  • Do not use after expiration date.

2.2 Administration

Each product package contains one PROLASTIN-C single use vial, one 20 mL vial of Sterile Water for Injection (diluent), one color-coded sterile transfer needle, and one sterile filter needle. Administer within three hours after reconstitution.

Reconstitution

Use aseptic technique.

  1. PROLASTIN-C and diluent should be at room temperature before reconstitution.
  2. Remove the plastic flip tops from each vial.
  3. Swab the exposed stopper surfaces with alcohol and allow surface to dry.
  4. Remove the plastic cover from the short end of the transfer needle. Insert the exposed end of the needle through the center of the stopper in the DILUENT vial.
  5. Remove the cover at the other end of the transfer needle by twisting it carefully.
  6. Invert the DILUENT vial and insert the attached needle into the PRODUCT vial at a 45° angle (Figure A below). This will direct the stream of diluent against the wall of the product vial and minimize foaming. The vacuum will draw the diluent into the PRODUCT vial.
  7. Remove the DILUENT bottle and transfer needle.
  8. Immediately after adding the diluent, swirl vigorously for 10-15 seconds to thoroughly break up cake then swirl continuously until the powder is completely dissolved (Figure B below). Some foaming will occur, but does not affect the quality of the product.
  9. Inspect the vial visually for particulate matter and discoloration prior to pooling and administration. A few small particles may occasionally remain after reconstitution. If particles are visible, remove by passage through a sterile filter (e.g., 15 micron filter) used for administering blood products (not supplied).
  10. Reconstituted product from several vials may be pooled into an empty, sterile IV solution container by using aseptic technique. A sterile filter needle is provided for this purpose.

Described here is one acceptable method of reconstitution. The product could also be reconstituted with other appropriate devices according to the manufacturer’s accepted procedure.

PROLASTIN-C Reconstitution Method
(click image for full-size original)

Shelf Life

PROLASTIN-C should be stored at temperatures not to exceed 25°C (77°F) for the period indicated by the expiration date on its label.

Special Precautions for Storage

Freezing should be avoided as breakage of the diluent bottle might occur.

3 DOSAGE FORMS AND STRENGTHS

PROLASTIN-C is supplied in 1000 mg single use vials with a separate 20 mL vial of Sterile Water for Injection, USP.

4 CONTRAINDICATIONS

PROLASTIN-C is contraindicated in IgA deficient patients with antibodies against IgA, due to the risk of severe hypersensitivity.

5 WARNINGS AND PRECAUTIONS

5.1 Sensitivity

Hypersensitivity reactions may occur. Should evidence of an acute hypersensitivity reaction be observed, the infusion should be stopped promptly and appropriate countermeasures and supportive therapy should be administered. (See Patient Counseling Information [17])

PROLASTIN-C may contain trace amounts of IgA. Patients with known antibodies to IgA, which can be present in patients with selective or severe IgA deficiency, have a greater risk of developing potentially severe hypersensitivity and anaphylactic reactions. PROLASTIN-C is contraindicated in patients with antibodies against IgA.

5.2 Viral Clearance

Products made from human plasma may carry a risk of transmitting infectious agents, e.g., viruses, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. In each of 2 randomized, double-blind studies in which the predecessor product, PROLASTIN® (Alpha1-Proteinase Inhibitor [Human]), was compared to other Alpha1 products, there was a single case of parvovirus B19 seroconversion in the PROLASTIN arms of each trial. In each case, it could not be determined whether parvovirus B19 had been acquired from PROLASTIN or from the community. However, during clinical studies with PROLASTIN-C, there were no reported treatment emergent cases of hepatitis B, hepatitis C, HIV or parvovirus B19 viral infections. Furthermore, the PROLASTIN-C process incorporates additional plasma safety and virus reduction measures that minimize the residual risk of virus transmission (See Description [11]).

The physician should discuss the risks and benefits of this product with the patient, before prescribing or administering it to a patient. (See Patient Counseling Information [17]). All infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Talecris Biotherapeutics, Inc. [1-800-520-2807].

6 ADVERSE REACTIONS

The most serious adverse reaction observed during clinical studies with PROLASTIN-C was an abdominal and extremity rash in one subject. The rash resolved subsequent to outpatient treatment with antihistamines and steroids. Two instances of a less severe, pruritic abdominal rash were observed upon rechallenge despite continued antihistamine and steroid treatment, which led to withdrawal of the subject from the trial.

The most common drug-related adverse reactions observed at a rate of ≥ 1% in subjects receiving PROLASTIN-C were chills, malaise, headache, rash, hot flush and pruritus.

6.1 Clinical Trials Experience

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

Two separate clinical studies were conducted with PROLASTIN-C: (1) A 20 week, open-label, single arm safety study in 38 subjects, and (2) A 16 week, randomized, double-blind, crossover pharmacokinetic comparability study vs. PROLASTIN in 24 subjects, followed by an 8 week open-label treatment with PROLASTIN-C. Thus, 62 subjects were exposed to PROLASTIN-C in clinical trials.

Adverse reactions considered drug related by the investigators occurring in 1.6% of subjects (one subject each) treated with PROLASTIN-C were malaise, headache, rash, hot flush, and pruritus. Drug related chills occurred in 3.2% (2 subjects) of PROLASTIN-C subjects.

Adverse events occurring irrespective of causality in ≥ 5% of subjects in the first 8 weeks of treatment are shown in Table 1. Adverse events which occurred in the first 8 weeks of treatment are shown in the table in order to control for the differing treatment durations of the safety and PK studies (20 weeks vs. two 8 week periods).

Table 1: Adverse Events Occurring in ≥ 5% of Subjects in the First 8 Weeks of Treatment Irrespective of Causality
PROLASTIN® -CNo. of subjects: 62 PROLASTIN® No. of subjects: 24
Adverse Event No. of subjects with AE(percentage of all subjects) No. of subjects with AE(percentage of all subjects)
Source: studies 11815 and 11816
Nausea 4 (6.5%) 0
Urinary Tract Infection 4 (6.5%) 0
Headache 3 (4.8%) 2 (8.3%)
Arthralgia 2 (3.2%) 2 (8.3%)

Table 2 below displays the overall adverse rate (> 0.5%), irrespective of causality, as a percentage of infusions received.

Table 2: Adverse Event Frequency as a % of all infusions (> 0.5%) Irrespective of Causality
PROLASTIN® -CNo. of infusions: 1132 PROLASTIN® No. of infusions: 192
Adverse Event No. of AE(percentage of all infusions) No. of AE(percentage of all infusions)
Source: studies 11815 and 11816
Upper respiratory tract infection 9 (0.8%) 1 (0.5%)
Urinary tract infection 8 (0.7%) 0
Nausea 7 (0.6%) 0
Headache 4 (0.4%) 3 (1.6%)
Arthralgia 2 (0.2%) 2 (1.0%)

Table 3 below displays the overall rates of adverse events (≥ 5%), in the first eight weeks of treatment, that began during or within 72 hours of the end of an infusion of PROLASTIN-C or PROLASTIN.

Table 3: Adverse Events Occurring in ≥ 5% of Subjects during or within 72 hours of the end of an infusion, in the First 8 Weeks of Treatment Irrespective of Causality
PROLASTIN® -CNo. of subjects: 62 PROLASTIN® No. of subjects: 24
Adverse Event No. of subjects with AE(percentage of all subjects) No. of subjects with AE(percentage of all subjects)
Source: studies 11815 and 11816
Urinary Tract Infection 4 (6.5%) 0
Headache 3 (4.8%) 2 (8.3%)

Ten exacerbations of chronic obstructive pulmonary disease were reported by 8 subjects in the 24 week pharmacokinetic crossover study. During the 16 week double-blind crossover phase, 4 subjects (17%) had a total of 4 exacerbations during PROLASTIN-C treatment and 4 subjects (17%) had a total of 4 exacerbations during PROLASTIN treatment. Two additional exacerbations in 2 subjects (8%) occurred during the 8 week open label treatment period with PROLASTIN-C. The overall rate of pulmonary exacerbations during treatment with either product was 0.9 exacerbations per subject-year.

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