Plasminogen

Plasminogen is plasma-derived human plasminogen used for the treatment of plasminogen deficiency type 1 (hypoplasminogenemia).

• Plasminogen is available under the following different brand names: Ryplazim, plasminogen, human-tvmh.

Common side effects of Plasminogen include:

• Abdominal pain,
• Bloating,
• Nausea,
• Fatigue,
• Pain in extremities,
• Bleeding,
• Constipation,
• Dry mouth,
• Headache,
• Dizziness,
• Joint pain, and
• Back pain.

Serious side effects of Plasminogen include:

• Bleeding,
• Gastrointestinal bleeding,
• Genitourinary bleeding,
• Nosebleed,
• Bleeding gums, and
• Bleeding at the injection site

Rare side effects of Plasminogen include:

• None 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out. 

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Injection, of lyophilized powder for reconstitution

• 68.8 mg/vial (5.5 mg/mL after reconstitution)

Plasminogen Deficiency Type 1

Adult and pediatric dosage

• 6.6 mg/kg intravenous every 2-4 days
• Calculate total infusion volume.
• Final concentration following reconstitution: 5.5 mg/mL.
• 6.6 mg/kg divided by 5.5 mg/mL = 1.2 mL/kg
• Infusion volume (mL) = body weight (kg) x 1.2 mL/kg
• Number of vials = infusion volume (mL) X 0.08 (round up the estimated number of vials)
• Determine dose frequency.
  • Obtain a baseline plasminogen activity level; if receiving plasminogen supplementation with fresh frozen plasma, allow for a 7-day washout period beforehand
  • Initiate dosing every 3 days.
  • Obtain a trough plasminogen activity level approximately 72 hours after the initial dose and before the second dose (same time of day as the initial dosing)
  • If the plasminogen activity level is below 10% above the baseline plasminogen level, change the dosing frequency to every 2 days.
  • If the plasminogen activity level is above 10 and below 20% above baseline, maintain dosing frequency every 3 days.
  • If the plasminogen activity level is above 20% above baseline, change the dosing frequency to every 4 days.
  • Maintain dosing frequency as determined above for 12 weeks while treating active lesions.
  • If lesions resolve by 12 weeks, continue at the same dosing frequency, and monitor for new or recurrent lesions every 12 weeks.
  • If lesions do not resolve by 12 weeks, or there are new or recurrent lesions, increase the dosing frequency in 1-day increments every 4-8 weeks up to every 2 days dosing while reassessing clinical improvement until lesion resolution or until the lesions stabilize without further worsening; if desired clinical change does not occur by 12 weeks, check trough plasminogen activity level.
• Lesions not resolved by 12 weeks.
  • If the trough plasminogen activity level is above 10% above the baseline trough level, consider other treatment options, such as surgical removal of the lesion in addition to plasminogen treatment.
  • If the trough plasminogen activity level is below 10% above the baseline trough level, obtain a second trough plasminogen activity level to confirm; if the low plasminogen activity level is confirmed in combination with no clinical efficacy, consider discontinuing plasminogen treatment owing to the possibility of neutralizing antibodies.

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Plasminogen has no noted serious interactions with any other drugs.
• Plasminogen has no noted severe interactions with any other drugs.
• Plasminogen has no noted moderate interactions with any other drugs.
• Plasminogen has no noted minor interactions with any other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice or health questions or concerns.

Contraindications

• Hypersensitivity

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Plasminogen?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Plasminogen?”

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 the 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 the risk of transmitting infection agents; report any infection thought to be possibly transmitted by this product to Prometic at 1-800-735-4086 and [email protected], 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 the 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 hours after infusion.
  • Seek emergency care if uncontrolled bleeding develops (. e, bleeding that persists above 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 above 4 hours after the first dose.
• Laboratory abnormalities
  • Patients receiving plasminogen may have elevated levels of D-dimer in the blood.
  • Interpret D-dimer levels with caution in patients being screened for venous thromboembolism (VTE); elevated levels may be associated with the 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 and Lactation

• 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 its presence in human milk, effects on breastfed infants, or effects on milk production.