Ryplazim (plasminogen, human-tvmh)

It isessential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

For IV use after reconstitution only.

Plasminogen, human-tmvh lyophilized powder should be reconstituted as directed by the manufacturer to provide a 5.5-mg/mL solution. The solution should be prepared within 3 hours of administration. The prepared dose of plasminogen, human-tmvh should be administered slowly over 10-30 minutes (i.e., approximately 1 mL every 12 seconds) into a peripheral vein using an appropriately sized administration syringe connected through a syringe disc filter to a butterfly infusion set.

The recommended dosage of plasminogen, human-tmvh for the treatment of plasminogen deficiency type 1 in pediatric patients is 6.6 mg/kg administered IV every 2-4 days. The frequency of administration is based on plasminogen activity level and clinical status of lesions. The manufacturer's labeling should be consulted for detailed information on interpretation of plasminogen activity level and determination of dosing frequency.

The recommended dosage of plasminogen, human-tmvh for the treatment of plasminogen deficiency type 1 in adults is 6.6 mg/kg administered IV every 2-4 days. The frequency of administration is based on plasminogen activity level and clinical status of lesions. The manufacturer's labeling should be consulted for detailed information on interpretation of plasminogen activity level and determination of dosing frequency.

No dosing information is available for this tab.

No dosing information is available for this tab.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Plasminogen/Anticoagulants; Antiplatelets

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Bleeding has been reported with the use of plasminogen.(1)

CLINICAL EFFECTS: Concurrent use of plasminogen with either anticoagulants or antiplatelets may increase the risk of active bleeding during plasminogen therapy, including bleeding from mucosal disease-related lesions that may manifest as gastrointestinal (GI) bleeding, hemoptysis, epistaxis, vaginal bleeding, or hematuria.(1)

PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs).

PATIENT MANAGEMENT: Patients receiving concurrent therapy with plasminogen and anticoagulants and/or antiplatelets should be closely monitored during plasminogen therapy for active bleeding from mucosal disease-related lesions, including GI bleeding, hemoptysis, epistaxis, vaginal bleeding, or hematuria.(1) Prior to initiation of treatment with plasminogen, confirm healing of lesions or wounds suspected as a source of a recent bleeding event. Monitor patients during and for 4 hours after infusion when administering plasminogen with concurrent anticoagulants, antiplatelet drugs, or other agents which may interfere with normal coagulation.(1) If patient experiences uncontrolled bleeding (defined as any gastrointestinal bleeding or bleeding from any other site that persists longer than 30 minutes), seek emergency care and discontinue plasminogen immediately.(1) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory tests (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug.

DISCUSSION: Plasminogen has not been studied in patients at an increased risk of bleeding. Bleeding has been reported with plasminogen in a two single-arm, open-label clinical trials as well as in compassionate use programs. The incidence of hemorrhage in patients with Plasminogen Deficiency Type 1 was 16% (3/19 patients).(1) One of the bleeding events occurred two days after receiving the second dose of plasminogen in a patient with a recent history of GI bleeding due to gastric ulcers. The patient received plasminogen through a compassionate use program and the dose was 6.6 mg/kg body weight every 2 days. Endoscopy showed multiple ulcers with one actively bleeding ulcer near the pylorus.(1)

Plasminogen, human-tmvh is contraindicated in patients with known hypersensitivity to plasminogen or to other components of plasminogen, human-tmvh.

There are no contraindication contraindications for this drug.

• Increased risk of bleeding

There are no moderate contraindications for this drug.

The most frequent (incidence >=10%) adverse reactions in clinical trials were abdominal pain, bloating, nausea, fatigue, extremity pain, hemorrhage, constipation, dry mouth, headache, dizziness, arthralgia, and back pain.

Less Frequent

• Sloughing of tissue at mucosal lesion

Rare or Very Rare

• Hypersensitivity drug reaction

More Frequent

• Abdominal distension
• Acute abdominal pain
• Arthralgia
• Back pain
• Constipation
• Dizziness
• Fatigue
• Headache disorder
• Hemorrhage
• Nausea
• Pain in extremities
• Xerostomia

No enhanced messaging available.

The safety and efficacy of plasminogen, human-tmvh have been established in pediatric patients. Use of plasminogen, human-tmvh is supported by the two clinical trials and by expanded access and compassionate use programs that included 18 pediatric patients 11 months to 17 years of age.

Risk Summary: There are no clinical trials of plasminogen, human-tmvh use in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with plasminogen, human-tmvh to assess whether it can cause fetal harm when administered to a pregnant woman. In the United States, the background risk of major birth defects is about 3%, and miscarriage occurs in up to 20% of clinically recognized pregnancies.

Endogenous plasminogen is distributed into human milk; however, there is no information available on the presence of plasminogen, human-tmvh in human milk, the effects on the breast-fed infant, or the effects on milk production. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for plasminogen, human-tmvh and any potential adverse effects on the breast-fed infant from plasminogen, human-tmvh or from the underlying maternal condition.

The safety and efficacy of plasminogen, human-tmvh have not been established in geriatric patients. Clinical studies of plasminogen, human-tmvh for this indication did not include patients 65 years of age and older. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.