Version May 2024
Plasminogen deficiency type 1 (hypoplasminogenemia):
Note: If the patient is receiving plasminogen supplementation with fresh frozen plasma, allow for a 7-day washout period before obtaining baseline plasminogen activity level.
IV:
Initial:6.6 mg/kg; obtain plasminogen activity level prior to the initial dose and 72 hours after, then redose as follows:
If plasminogen activity level increase is <10% from baseline: Administer 6.6 mg/kg every 2 days for 12 weeks while assessing for clinical improvement of lesion(s).
If plasminogen activity level increase is ≥10% and ≤20% from baseline: Administer 6.6 mg/kg every 3 days for 12 weeks; if lesions do not resolve by 12 weeks or there are new lesions, increase dose frequency to every-2-day dosing while assessing for clinical improvement of lesion(s).
If plasminogen activity level increase is >20% from baseline: Administer 6.6 mg/kg every 4 days for 12 weeks; if lesions do not resolve by 12 weeks or there are new lesions, increase dose frequency in 1-day increments every 4 to 8 weeks up to every-2-day dosing while assessing for clinical improvement of lesion(s).
Maintenance:
If lesions resolve by 12 weeks: Continue 6.6 mg/kg at the same frequency (eg, every 2 to 4 days) and monitor for new or recurrent lesions every 12 weeks.
If lesions do not resolve by 12 weeks after titrating to a dosage frequency of every 2 days: Check trough plasminogen activity level and proceed as follows:
Trough plasminogen activity level increase is ≥10% from baseline: Consider other treatment options.
Trough plasminogen activity level increase is <10% from baseline: Obtain a second trough level to confirm low plasminogen activity level and consider discontinuing therapy due to possibility of neutralizing antibodies.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing; use with caution starting at the low end of the dosage range (eg, administer every 4 days to begin therapy).
(For additional information see "Human plasma-derived plasminogen: Pediatric drug information")
Plasminogen deficiency type 1 (hypoplasminogenemia):
Note: Obtain plasminogen activity level prior to the initial dose (baseline); if the patient is receiving plasminogen supplementation with fresh frozen plasma, allow for a 7-day washout period before obtaining baseline plasminogen activity level.
Infants, Children, and Adolescents: IV: Initial: 6.6 mg/kg/dose; frequency is determined by plasminogen activity level obtained ~72 hours after initial dose as follows:
If plasminogen activity level is >20% above baseline: IV: 6.6 mg/kg/dose every 4 days for 12 weeks. If lesions resolve by 12 weeks, continue a maintenance dose of 6.6 mg/kg/dose every 4 days and monitor for new or recurrent lesions every 12 weeks. If lesions do not resolve or there are new lesions after 12 weeks, increase dose frequency in 1-day increments every 4 to 8 weeks up to every-2-day dosing while assessing for clinical improvement of lesion(s).
If plasminogen activity level is ≥10 and ≤20% above baseline: IV: 6.6 mg/kg/dose every 3 days for up to 12 weeks. If lesions resolve by 12 weeks, continue a maintenance dose of 6.6 mg/kg/dose every 3 days and monitor for new or recurrent lesions every 12 weeks. If lesions do not resolve or there are new lesions after 12 weeks, increase dose frequency to every-2-day dosing while assessing for clinical improvement of lesion(s).
If plasminogen activity level is <10% above baseline: IV: 6.6 mg/kg/dose every 2 days for up to 12 weeks while assessing for clinical improvement of lesion(s). If lesions resolve by 12 weeks, continue a maintenance dose of 6.6 mg/kg/dose every 2 days and monitor for new or recurrent lesions every 12 weeks.
If lesions do not resolve or there are new lesions after 12 weeks at a dosing frequency of every 2 days: Check trough plasminogen activity level and proceed as follows:
Trough plasminogen activity level increase is ≥10% from baseline: Consider other treatment options.
Trough plasminogen activity level increase is <10% from baseline: Obtain another trough to confirm then discontinue therapy due to possibility of neutralizing antibodies.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Gastrointestinal: Abdominal pain, bloating, constipation, gastric dilation, nausea, xerostomia
Hematologic & oncologic: Hemorrhage
Immunologic: Antibody development
Nervous system: Dizziness, fatigue, headache
Neuromuscular & skeletal: Arthralgia, back pain, limb pain
Hypersensitivity to plasminogen or any component of the formulation.
Concerns related to adverse effects:
• Antibody formation: Neutralizing antibodies (inhibitors) to plasminogen may develop. Monitor for the loss of clinical efficacy (eg, new or recurrent lesions) and confirm that adequate plasminogen activity levels have been achieved and are being maintained (eg, plasminogen activity trough levels).
• Bleeding: May lead to bleeding or worsen active bleeding. Prior to treatment initiation, confirm healing of lesions or wounds from recent bleeding event. Monitor patients during and after infusion when administering to patients with bleeding diatheses or taking anticoagulants, antiplatelets, or other agents that may interfere with coagulation. Discontinue use if uncontrollable bleeding occurs.
• Hypersensitivity reactions: Hypersensitivity reactions, including anaphylaxis, may occur. If symptoms occur, discontinue therapy and administer appropriate treatment.
• Tissue sloughing: Tissue sloughing at mucosal sites (eg, GI, genitourinary, respiratory) may occur after treatment initiation resulting in bleeding or organ obstruction. Patients with GI and genitourinary lesions may experience tissue sloughing that causes pain, bleeding, or passage of tissue from affected organ systems. Patients with tracheobronchial lesions may experience tissue sloughing; monitor patients with confirmed/suspected airway disease for airway obstruction or hemoptysis.
Dosage form specific issues:
• Human plasma: Product of human plasma; may potentially contain infectious agents (eg, viruses, the variant Creutzfeldt-Jakob disease [vCJD] agent and, theoretically, the Creutzfeldt-Jakob disease [CJD] agent) that could transmit disease. Screening of donors, as well as testing and/or inactivation or removal of certain viruses, reduces the risk. Infections thought to be transmitted by this product should be reported to the manufacturer.
Other warnings/precautions:
• Appropriate use: Initiate treatment in a clinical setting with personnel trained in airway management and respiratory equipment readily available.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Ryplazim: 68.8 mg (1 ea)
No
Solution (reconstituted) (Ryplazim Intravenous)
68.8 mg (per each): $2,476.80
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
IV: Administer slow IV push (~5 mL/minute) over 10 to 30 minutes through a syringe disc filter (eg, Baxter Supor 5-micron syringe filter or equivalent).
Administer via a dedicated infusion line; do not administer with other medications. Attach the syringe disc filter to a separate prefilled syringe of NS and infusion tubing with butterfly needle. Inject NS through the syringe disc filter and butterfly needle tubing to remove air bubbles. Remove the NS syringe. Attach the syringe containing plasminogen (human) to the syringe disc filter and tubing.
Parenteral: IV: For IV use only. Must be administered using a syringe disc filter and infusion tubing with butterfly needle. Prepare the filter and infusion tubing with butterfly needle by attaching to a prefilled NS syringe and injecting NS through to remove air bubbles. Remove the NS syringe leaving the disc filter and butterfly tubing together; attach the syringe containing plasminogen (human) to the syringe disc filter and tubing. Administer slowly over 10 to 30 minutes (~5 mL/minute) through a syringe disc filter using a dedicated infusion line. Do not coinfuse with other medications. If severe or life-threatening hypersensitivity reactions occur, immediately discontinue infusion and provide emergency care.
Plasminogen deficiency type 1 (hypoplasminogenemia): Treatment of patients with plasminogen deficiency type 1 (hypoplasminogenemia).
Plasminogen may be confused with pooled plasma or plasma protein fraction.
None known.
There are no known significant interactions.
Patients diagnosed with plasminogen deficiency type 1 (hypoplasminogenemia) may have pseudomembranes that cover the vagina (Celkan 2017). Treatment with plasminogen (human) improves or resolves vaginal pseudomembranous lesions (Shapiro 2018). Vaginal bleeding may occur with treatment.
Animal reproduction studies have not been conducted.
Endogenous plasminogen is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Plasminogen activity level (at baseline, 72 hours after initial dose, and as clinically indicated); monitor patients with bleeding diatheses and taking medications that interfere with normal coagulation during the infusion and for 4 hours after; monitor patients with confirmed or suspected airway disease with tracheobronchial lesions for development of airway obstruction or hemoptysis for ≥4 hours after receiving first dose.
Temporarily increases plasminogen levels in blood, thereby providing a temporary correction of the plasminogen deficiency and reduction or resolution of extravascular fibrinous lesions.
Note: Data are for adult and pediatric patients combined.
Onset of action: Mean absolute plasminogen activity reached physiological levels (70% to 130%) immediately after the first infusion.
Duration of action: Plasminogen activity sustained for ~24 hours after administration and remained an absolute 10% above baseline for 72 hours after initial dosing and for 96 hours after 12 weeks of therapy.
Distribution: Vss: 63.3 mL/kg (after first dose); 49.3 mL/kg (after week 12).
Half-life elimination: 34 hours (after first dose); 39.2 hours (after week 12).
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