plasminogen (Rx)

>10%

Abdominal pain (16%)

Gastric dilation (16%)

Nausea (16%)

Fatigue (16%)

Pain in extremity (16%)

Hemorrhage (16%)

Constipation (11%)

Dry mouth (11%)

Headache (11%)

Dizziness (11%)

Arthralgia (11%)

Back pain (11%)

Contraindications

Hypersensitivity

Cautions

Hypersensitivity reactions, including anaphylaxis, may occur

Formation of neutralizing antibodies to plasminogen following administration has not been reported to date; monitor for loss of clinical efficacy as manifested by development of new or recurrent lesions; obtain plasminogen activity trough levels to confirm that adequate plasminogen activity levels have been achieved and are being maintained

Human plasma-derived products carry risk of transmitting infection agents; report any infection thought to be possibly transmitted by this product to Prometic at 1-800-735-4086 and prometicsmb@continuumindia.com, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

Bleeding

• May worsen active bleeding not related to disease lesions
• Patients with plasminogen deficiency type 1 may bleed from active mucosal disease related lesions during treatment
• Depending on the lesion sites, this may manifest as GI bleeding, hemoptysis, epistaxis, vaginal bleeding, or hematuria
• Before initiating, confirm healing of lesions or wounds suspected as a source of recent bleeding events
• May prolong or worsen bleeding in patients with bleeding diatheses or if taking anticoagulants and/or antiplatelet drugs and other agents that may interfere with normal coagulation; monitor during and for 4 hr after infusion
• Seek emergency care if uncontrolled bleeding develops (ie, bleeding that persists >30 minutes) and discontinue immediately

Tissue sloughing

• Tissue sloughing at mucosal sites may occur as plasminogen activity levels are restored to physiological levels and fibrinolysis occurs
• Lesions in the respiratory, GI, and GU systems may slough following treatment, resulting in bleeding or organ obstruction
• Patients with tracheobronchial lesions may develop airway obstruction or hemoptysis; closely monitor patients with either confirmed or suspected airway disease as manifested by cough, wheezing, shortness of breath, or dysphonia; initiate in an appropriate clinical setting with personnel trained in airway management and readily available respiratory support equipment; monitor at-risk patients for ≥4 hr after first dose

Laboratory abnormalities

• Patients receiving plasminogen may have elevated levels of D-dimer in blood
• Interpret D-dimer levels with caution in patients being screened for venous thromboembolism (VTE); elevated levels may be associated with physiological activity of plasminogen (fibrinolysis of ligneous lesions) and not indicative of VTE
• Consider other tests to screen for VTE, as D-dimer levels will lack interpretability

Pregnancy

There are no clinical trials regarding use in pregnant females

No animal reproductive and developmental toxicity studies have been conducted

Lactation

Endogenous plasminogen is excreted in human milk; however, data are unavailable regarding presence in human milk, effects on breastfed infants, or effects on milk production

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Plasma-derived human plasminogen; treatment temporarily increases plasminogen blood levels

Plasminogen is a naturally occurring protein synthesized by the liver and circulates in the blood

Activated plasminogen, plasmin, is a fundamental component of the fibrinolytic system, blood clot lysis, and extravasated fibrin clearance

Plasminogen is vital in wound healing, cell migration, tissue remodeling, angiogenesis, and embryogenesis

Plasminogen deficiency marked by low plasminogen levels results in various rare conditions (eg, ligneous conjunctivitis); plasminogen replenishes deficient levels in the body

Distribution

Vd (first dose): 63.3 mL/kg

Elimination

Half-life: 34 hr (first dose); 39.2 (week 12)

IV Incompatibilities

Do not mix with other medications

IV Preparation

Prepare within 3 hr of administration

Reconstitution

• Allow vial(s) to equilibrate to room temperature before reconstitution (≥15 minutes if stored at 5ºC); do not refrigerate after reconstitution
• Sterilize surface of rubber stoppers with alcohol wipes and allow to dry
• Using a 20-mL sterile syringe with a sterile 18- to 22-gauge needle, withdraw 12.5 mL of sterile water for injection (SWFI) for each vial being reconstituted

• 10-mL SWFI vials

  • If using 10-mL vials of SWFI, each vial of plasminogen requires two 10-mL vials of SWFI
  • Withdraw 9 mL of SWFI from the first 10-mL vial and discard the first needle; attach a new 18- to 22-gauge sterile needle and withdraw 3.5 mL SWFI from the second 10-mL vial to equal 12.5 mL
  • Discard used SWFI vials
  • Repeat process for each vial needing to be reconstituted
  • If using larger volume SWFI vials, only 1 syringe is needed
• Using the same needle and syringe, gently and slowly add the 12.5 mL of SWFI to the plasminogen vial, directing the stream down toward the side to prevent foaming; discard the used syringe and needle(s)
• Gently swirl vial by rotating it slowly to ensure that lyophilized powder dissolves fully; do not shake
• Plasminogen should fully dissolve within 10 minutes; discard if not fully dissolved after 10 minutes

Prepare syringe for administration

• Select an administration syringe of appropriate volume based on infusion volume calculated
• Note: A 30-mL syringe can hold up to 2 reconstituted vials
• Using administration syringe(s) with 18- to 22-gauge needle(s), slowly withdraw the reconstituted plasminogen from each vial to administer the exact infusion volume

IV Administration

For IV use only through a syringe disc filter; 1 filter needed per infusion

Inspect solution; do not use if discoloration or particulate matter observed

Administer in separate infusion line

Draw 10 mL of normal saline into a different syringe; push plunger down to remove any air bubbles

Attach syringe disc filter to the prefilled syringe of normal saline and infusion tubing

Prime tubing with the normal saline through the syringe disc filter and butterfly needle tubing to remove any air bubbles

Remove normal saline syringe; keep syringe disc filter attached to the tubing, as it is required for plasminogen administration; discard normal saline syringe

Attach the administration syringe containing plasminogen to the syringe disc filter that is connected to the butterfly needle tubing

Choose a peripheral vein (eg, antecubital or dorsum of hand); clean the injection site (do not blow on it); insert butterfly infusion set needle in peripheral vein, and tape in place

Infuse total dose slowly over 10-30 minutes (~5 mL/min); push plunger of the syringe ~1 mL every 12 seconds

Discard unused solution and administration equipment following administration

Storage

Store at 2-25ºC (36-77ºF) in its original carton until ready to use

Do not freeze

Once reconstituted, must be administered within 3 hr; do not refrigerate after reconstitution

Store diluent and syringe disc filters at 20-25ºC (68-77ºF)