Elapegademase-Lvlr
FDA Drug Information • Also known as: Revcovi
- Brand Names
- Revcovi
- Route
- INTRAMUSCULAR
- Dosage Form
- INJECTION
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION Elapegademase-lvlr is a recombinant adenosine deaminase (rADA) based on bovine amino acid sequence, conjugated to monomethoxypolyethylene glycol (mPEG). rADA is manufactured in E. coli and is covalently conjugated to mPEG with a succinimidyl carbamate linker to produce methoxypolyethylene glycol recombinant adenosine deaminase (SC-PEG rADA). The approximate molecular weight of elapegademase-lvlr (SC-PEG rADA) is 113 KDa. REVCOVI (elapegademase-lvlr) injection is a sterile, preservative free, clear, colorless solution for intramuscular use supplied in single-dose vials. Each vial provides 1.5 mL of solution containing 2.4 mg elapegademase-lvlr (1.6 mg/mL), sodium chloride (12.75 mg), sodium phosphate dibasic heptahydrate (12.7 mg), sodium phosphate monobasic monohydrate (3.81 mg), and Water for Injection, USP. The pH is 6.9.
What Is Elapegademase-Lvlr Used For?
1 INDICATIONS AND USAGE REVCOVI is indicated for the treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in pediatric and adult patients. REVCOVI is a recombinant adenosine deaminase indicated for the treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in pediatric and adult patients. ( 1 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Patients transitioning from Adagen to REVCOVI : The starting dose of REVCOVI is 0.2 mg/kg weekly, intramuscularly. See Full Prescribing Information (FPI) for conversion formula from Adagen to REVCOVI. ( 2.1 ) Adagen-naïve patients : The starting dose of REVCOVI is 0.4 mg/kg weekly based on ideal body weight or actual weight whichever is greater, divided into two doses (0.2 mg/kg twice a week), intramuscularly. ( 2.1 ) For complete information, maintenance dosing and therapeutic monitoring, see FPI. ( 2.1 , 2.3 ) REVCOVI is for intramuscular injection only. See FPI for administration instructions. ( 2.2 ) 2.1 Recommended Dosage Patients transitioning from Adagen to REVCOVI If a patient's weekly Adagen dose is unknown, or a patient's weekly Adagen dose is at or lower than 30 U/kg, the recommended minimum starting dose of REVCOVI is 0.2 mg/kg, intramuscularly, once a week. If a patient's weekly Adagen dose is above 30 U/kg, an equivalent weekly REVCOVI dose (mg/kg) should be calculated using the following conversion formula: REVCOVI dose in mg/kg = Adagen dose in U/kg 150 Subsequent doses may be increased by increments of 0.033 mg/kg weekly if trough ADA activity is under 30 mmol/hr/L, trough deoxyadenosine nucleotides (dAXP) are above 0.02 mmol/L, and/or the immune reconstitution is inadequate based on the clinical assessment of the patient. The total weekly dose may be divided into multiple intramuscular (IM) administrations during a week. Adagen-naïve patients The starting weekly dose of REVCOVI is 0.4 mg/kg based on ideal body weight or actual weight whichever is greater, divided into two doses (0.2 mg/kg twice a week), intramuscularly, for a minimum of 12 to 24 weeks until immune reconstitution is achieved. After that, the dose may be gradually adjusted down to maintain trough ADA activity over 30 mmol/hr/L, trough dAXP level under 0.02 mmol/L, and/or to maintain adequate immune reconstitution based on clinical assessment of the patient. The optimal long-term dose and schedule of administration should be established by the treating physician for each patient individually and may be adjusted based on the laboratory values for trough ADA activity, trough dAXP level, and/or on the treating physician's medical assessment of the patient's clinical status . 2.2 Administration Instructions REVCOVI is for IM injection only. Follow sterile IM administration technique guidelines appropriate to the patient's age and anatomy (i.e. choice of needle gauge and length, site of administration). Take precautions not to inject into or near an artery or nerve. Alternate the injection site periodically. Preparation of Injection and Procedure Instructions REVCOVI should not be diluted nor mixed with any other drug prior to administration. Visually inspect REVCOVI for particulate matter and discoloration prior to administration. REVCOVI is a clear, colorless solution; discard if solution is discolored, cloudy or contains particulate...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The most common adverse reactions reported were cough (50%) and vomiting (33%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Chiesi USA, Inc. at 1-888-661-9260 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. REVCOVI was administered intramuscularly in two prospective, open-label, single-arm, multi‑center studies to evaluate efficacy, safety, tolerability, and pharmacokinetics in patients with ADA-SCID: Study 1 was performed in the US and Study 2 was performed in Japan [see Clinical Studies ( 14 )] . Overall, 10 patients were treated and adverse reactions reported are summarized below. Study 1 Study 1 is a one-way crossover study, conducted in the US, to evaluate the safety, efficacy, and pharmacokinetics of REVCOVI in patients with ADA‑SCID who were receiving therapy with Adagen. Six patients, 8 to 37 years of age enrolled in the study. Patients' exposure to REVCOVI ranged from 2 weeks to 146 weeks. No deaths were reported and one patient discontinued treatment due to injection site pain associated with an earlier drug product formulation that was consequently modified. The most common adverse reactions were cough (3/6 patients) and vomiting (2/6 patients). Other adverse reactions that were reported in one patient each were: abdominal pain upper, arthralgia, asthenia, cerumen impaction, conjunctivitis, convulsion, dental caries, diarrhea, ear canal irritation, ear lobe infection, epistaxis, fatigue, fungal skin infection, gait disturbance, gastrointestinal infection, groin abscess, hematochezia, haemophilus infection (pulmonary), hemoptysis, influenza, injection site discomfort, laceration, lymphadenopathy, migraine, nasal edema, nausea, nephrolithiasis, oral candidiasis, oropharyngeal pain, otitis externa, productive cough, rash, stoma site infection, swelling face, tooth abscess, tooth extraction and upper respiratory tract infection, regardless of investigator causality assessment. Study 2 Study 2 is a single-arm clinical study that was conducted to assess the safety, efficacy and pharmacokinetics of REVCOVI in patients with ADA-SCID. Four patients 3.4 months to 25 years of age, all Asian, were enrolled in the study and received REVCOVI. Three patients received REVCOVI for 21 weeks and one patient received REVCOVI for 15 weeks. One death due to CMV pneumonitis and respiratory failure was observed in an infant, who had also experienced pulmonary hemorrhage, respiratory failure and upper respiratory tract infection that represented serious adverse events. Neutropenia was a serious adverse reaction reported by one of the patients. There were 22 reported adverse events for four patients. Most common adverse events were respiratory infections (2/4 patients). 6.2 Immunogenicity As with all therapeutic proteins, there is potential for immunogenicity. The immunogenicity results from Study 1 and Study 2 suggest that patients who previously received Adagen may present an immunologic response to REVCOVI. Therefore, monitoring for changes in ADA levels during REVCOVI treatment is recommended. [see Dosage and Administration ( 2.3 )] The observed incidence of antibodies (including neutralizing antibodies) is dependent on assay sensitivity and specificity, assay methodology, and concomitant medications. Therefore, the comparison of the incidence of antibodies to REVCOVI with the incidence of antibodies to other products may be misleading. 6.3 Postmarketing Experience with ADAGEN The following postmarketing adverse reactions were voluntarily reported for Adagen, the same class of enzyme replacement therapy used in the treatment of ADA-SCID, and may also be seen with REVCOVI treatment: Hematologic: hemolytic anemia,...
Drug Interactions
7 DRUG INTERACTIONS The drug interaction potential of REVCOVI is not known.
Contraindications
4 CONTRAINDICATIONS None. None ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Adequate and well-controlled studies with REVCOVI have not been conducted in pregnant women to inform a drug-associated risk. Animal reproduction studies have not been conducted with REVCOVI. It is not known whether REVCOVI can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human No pregnancy was reported for any patients receiving REVCOVI. There are two reports of confirmed cases of successful pregnancy and delivery in ADA-SCID patients treated with Adagen (the same class of enzyme replacement therapy used in the treatment of ADA-SCID). No teratogenic effects of Adagen were reported. For patients treated with REVCOVI, more frequent monitoring of the health status for both the mother during pregnancy and the development of the offspring is recommended.
Overdosage
10 OVERDOSAGE There are no reports of administration of REVCOVI in excess of the prescribed doses. The highest weekly prescribed dose administered in the clinical studies was 0.4 mg/kg. In nonclinical studies, there was no evidence of toxicity related to study drug at doses up to 1.8-fold the clinical dose (based on mean human AUC normalized to the dose of REVCOVI administered per patient), except for a slight increase in activated partial thromboplastin time (APTT).
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING REVCOVI (elapegademase-lvlr) injection, 2.4 mg/1.5 mL (1.6 mg/mL), is a sterile, preservative free, clear, colorless solution for intramuscular use available as one single-dose vial per carton (NDC 10122-502-01). The vial stopper is not made with natural rubber latex. Single-dose vial; do not re-use the vial. Discard unused portions. Store REVCOVI in the refrigerator between 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze or shake. REVCOVI should not be used if there are any indications that it may have been frozen.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.