Conestat alfa

Conestat alfa
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aparna Vuppala, M.B.B.S. [2]

Disclaimer

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Overview

Conestat alfa is a C1 esterase inhibitor that is FDA approved for the treatment of acute attacks in adult and adolescent patients with hereditary angioedema (HAE). Common adverse reactions include abdominal pain, diarrhea, nausea, headache, pain in throat.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Hereditary angioedema

• conestat alfa is a C1 esterase inhibitor [recombinant] indicated for the treatment of acute attacks in adult and adolescent patients with hereditary angioedema (HAE).
• Limitation of Use: Effectiveness was not established in HAE patients with laryngeal attacks.

• For intravenous use after reconstitution only.

Recommended Dosing

• Initiate treatment with conestat alfa under the supervision of a qualified healthcare professional experienced in the treatment of HAE.
• Appropriately trained patients may self-administer upon recognition of an HAE attack.
• The recommended dose of conestat alfa is 50 IU per kg with a maximum of 4200 IU to be administered as a slow intravenous injection over approximately 5 minutes.

• If the attack symptoms persist, an additional (second) dose can be administered at the recommended dose level. Do not exceed 4200 IU per dose. No more than two doses should be administered within a 24 hour period.

This image is provided by the National Library of Medicine.

Preparation and Handling

• Store conestat alfa in the original carton and protect from light prior to reconstitution.
• Do not use after expiration date on the product vial label.
• Water for Injection is not included in the conestat alfa package.
• Use aseptic technique to reconstitute, mix the solution, and to combine the reconstituted solution from more than one vial .
• Do not mix or administer conestat alfa with other medicinal products or solutions.
• Discard all partially used vials after treatment.

Reconstitution

• Each package contains one single-use vial of conestat alfa. To reconstitute, the following are also required:
• Sterile Water for Injection (diluent) - At least 14 mL per vial of conestat alfa requiring reconstitution.

• Alcohol swab
• Syringe
• Commercially available vial adapter with vented vial spike and syringe luer lock or large bore needle. If using a syringe with vial adapter, use a new vial adapter for each vial of conestat alfa and diluent.

• The procedures below are provided as general guidelines for the reconstitution and administration of conestat alfa.

• Ensure that the conestat alfa vial and diluent vial are at room temperature.
• Remove the flip caps from the conestat alfa and diluent vials. Treat the vial stoppers with the alcohol swab and allow to dry.
• Using the syringe/needle or syringe/vial adapter, withdraw 14 mL of sterile water for injection from the diluent vial.
• Remove the syringe and transfer the diluent to the conestat alfa vial. Add the diluent slowly to avoid forceful impact on the powder. Swirl the vial slowly to mix and avoid foaming.
• Repeat this procedure using another 14 mL of diluent and a second vial of conestat alfa.
• If the same patient is to receive more than one vial, the contents of multiple vials may be pooled into a single administration device (i.e., syringe).
• Inspect conestat alfa visually for particulate matter and discoloration after reconstitution and prior to administration. The reconstituted solution should be colorless, clear, and free from visible particles. Do not use if the solution is cloudy, colored, or contains particulates.
• conestat alfa vial is for single-use only.
• Use the reconstituted product immediately, or within 8 hours stored at 2°C-8°C (36°F-46°F). Discard partially used vials.
• Do not freeze the reconstituted solution.

Administration

• Do not mix conestat alfa with other medicinal products. Administer conestat alfa by a separate infusion line.
• Use aseptic technique when administering conestat alfa.

• Follow recommended venipuncture guidelines for initiating intravenous therapy.
• Administer conestat alfa by slow intravenous injection over approximately 5 minutes.
• For self-administration, provide the patient with instructions and training for intravenous injection outside of a clinic setting so patients may self-administer conestat alfa upon recognition of symptoms of an HAE attack.
• After administration, immediately discard any unused product and all used disposable supplies in accordance with local requirements.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Conestat alfa in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Conestat alfa in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding FDA-Labeled Use of Conestat alfa in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Conestat alfa in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Conestat alfa in pediatric patients.

Contraindications

• conestat alfa is contraindicated in patients with a history of allergy to rabbits or rabbit-derived products.
• conestat alfa is contraindicated in patients with a history of life-threatening immediate hypersensitivity reactions to C1 esterase inhibitor preparations, including anaphylaxis.

Warnings

Hypersensitivity

• Severe hypersensitivity reactions may occur . The signs and symptoms of hypersensitivity reactions may include hives, generalized urticaria, tightness of the chest, wheezing, hypotension, and/or anaphylaxis during or after injection of conestat alfa. Should symptoms occur, discontinue conestat alfa and institute appropriate treatment. Because hypersensitivity reactions may have symptoms similar to HAE attacks, treatment methods should be carefully considered.

Thromboembolic Events

• Serious arterial and venous thromboembolic (TE) events have been reported at the recommended dose of plasma derived C1 esterase inhibitor products in patients with risk factors. Risk factors may include the presence of an indwelling venous catheter/access device, prior history of thrombosis, underlying atherosclerosis, use of oral contraceptives or certain androgens, morbid obesity, and immobility. Monitor patients with known risk factors for TE events during and after conestat alfa administration.

Adverse Reactions

Clinical Trials Experience

• The serious adverse reaction in clinical studies of conestat alfa was anaphylaxis.

• The most common adverse reactions (≥ 2%) reported in all clinical trials were headache, nausea, and diarrhea.

Clinical Trials Experience

• Because clinical trials are conducted under widely varying conditions, the 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 clinical practice.

• The conestat alfa clinical development program evaluated a combined total of 940 administrations in 236 subjects (symptomatic and non-symptomatic). In clinical studies, a total of 205 symptomatic HAE patients received treatment with conestat alfa for a combined total of 650 acute angioedema attacks. Among these HAE patients, 83 were treated for a single HAE attack and 122 were treated for multiple attacks.

• Three randomized, placebo-controlled clinical trials (RCTs) were conducted in which 137 patients experiencing acute HAE attacks received conestat alfa (either an initial 50 IU/kg or 100 IU/kg body weight dose) or placebo (saline solution).

• Table 2 shows all adverse reactions (ARs) in the RCTs, compared with the placebo group.

This image is provided by the National Library of Medicine.

• Integrated RCT and Open-Label Extension (OLE) Studies

• In a total of seven RCT and OLE studies, 205 patients experiencing acute HAE attacks were treated with conestat alfa for a total of 650 HAE attacks. Included in this population were 124 patients who were treated at the 50 IU/kg dosage strength for one or more attacks.

• Table 3 shows adverse reactions in ≥ 2% of patients in any conestat alfa group for the integrated dataset combining all seven RCT and OLE studies in patients experiencing acute HAE attacks.

This image is provided by the National Library of Medicine.

Immunogenicity

• As with all therapeutic proteins, there is potential for immunogenicity. Pre- and post-exposure samples from 205 HAE patients treated for 650 acute attacks with conestat alfa were tested for the antibodies against plasma-derived C1INH or rhC1INH and for antibodies against host-related impurities (HRI). Testing was performed prior to and after treatment of a first attack and subsequent repeated attacks at 7, 22 or 28, and 90 days after conestat alfa treatment.

• Prior to the first exposure to conestat alfa, the frequency of anti-C1INH antibodies varied from 1.2% to 1.6% of samples. After the first exposure, the frequency of anti-C1INH antibodies varied from 0.6% to1.0% of samples tested. After repeated exposures, the frequency of anti-C1INH antibodies varied from 0.5 to 2.2% of samples tested. The frequency of anti-HRI antibodies was 1.0% in pre-exposure samples, and after the first exposure varied from 3.5% to 4.6%. After repeated exposure, the frequency of anti-HRI antibodies varied from 5.7% to 17% of samples. At least 10% of subjects formed a specific antibody response to conestat alfa after five treated HAE attacks. No anti-C1INH neutralizing antibodies were detected. Observed anti-C1INH and anti-HRI antibodies were not associated with adverse clinical findings.

• The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to conestat alfa with the incidence of antibodies to other products may be misleading.

Postmarketing Experience

• Because postmarketing reporting of adverse reactions is voluntary and from a population of uncertain size, it is not always possible to reliably estimate the frequency of these reactions or establish a causal relationship to product exposure.

• Adverse reactions in HAE patients receiving conestat alfa include abdominal pain and rash.

Drug Interactions

There is limited information regarding Conestat alfa Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): B

• Studies performed in rats and rabbits at doses up to 12.5 times the human dose of 50 IU/kg could not exclude an effect on embryofetal development. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, conestat alfa should only be used during pregnancy if clearly needed.

Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Conestat alfa in women who are pregnant.

Labor and Delivery

• The safety and efficacy of conestat alfa administration prior to or during labor and delivery have not been established. Use only if clearly needed.

Nursing Mothers

• It is not known if conestat alfa is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when conestat alfa is administered to a nursing woman.

Pediatric Use

• The safety and efficacy of conestat alfa were evaluated in 17 adolescent patients (13-17 years of age) treated for 52 HAE attacks. Eight out of 17 (47%) adolescent patients experienced adverse reactions. No serious adverse reactions were reported in these patients. The most common reactions (occurring in at least 2 patients) were: abdominal pain, headache, and oropharyngeal pain.
• The clinical studies of conestat alfa included seven patients older than 65 years. The clinical studies included an insufficient number of patients in this age group to determine if they respond differently from younger patients.

Geriatic Use

There is no FDA guidance on the use of Conestat alfa in geriatric settings.

Gender

There is no FDA guidance on the use of Conestat alfa with respect to specific gender populations.

Race

There is no FDA guidance on the use of Conestat alfa with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Conestat alfa in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Conestat alfa in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Conestat alfa in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Conestat alfa in patients who are immunocompromised.

Administration and Monitoring

Administration

• Intravenous

Monitoring

There is limited information regarding Conestat alfa Monitoring in the drug label.

IV Compatibility

There is limited information regarding IV Compatibility of Conestat alfa in the drug label.

Overdosage

There is limited information regarding Chronic Overdose of Conestat alfa in the drug label.

Pharmacology

This image is provided by the National Library of Medicine.

Mechanism of Action

• C1 esterase inhibitor (C1INH) is a normal constituent of human blood and is one of the serine protease inhibitors (serpins). The primary function of C1INH is to regulate the activation of the complement and contact system pathways. Regulation of these systems is performed through the formation of complexes between the protease and the inhibitor, resulting in inactivation of both and consumption of the C1INH.

• C1INH exerts its inhibitory effect by irreversibly binding several proteases (target proteases) of the contact and complement systems. The effect of conestat alfa on the following target proteases was assessed in vitro: activated C1s, kallikrein, factor XIIa and factor XIa. Inhibition kinetics were found to be comparable with those observed for plasma-derived human C1INH.

• HAE patients have low levels of endogenous or functional C1INH. Although the events that induce attacks of angioedema in HAE patients are not well defined, it is thought that contact system activation, and resulting increased vascular permeability lead to the clinical manifestation of HAE attacks. Suppression of contact system activation by C1INH through the inactivation of plasma kallikrein and factor XIIa is thought to modulate vascular permeability by preventing the generation of bradykinin.

• Administration of conestat alfa increases plasma levels of functional C1INH activity.

Structure

• conestat alfa is a recombinant analogue of human complement component 1 esterase inhibitor for intravenous injection. conestat alfa is purified from the milk of transgenic rabbits, and supplied as a sterile, preservative-free, white/off-white lyophilized powder for reconstitution for injection. One IU of rhC1INH activity is defined as the equivalent of C1 esterase inhibiting activity present in 1 mL of pooled normal plasma.

• conestat alfa is a soluble, single-chain glycoprotein containing 478 amino acids, with a molecular mass of 68 kDa, of which approximately 22% comprises oligosaccharide structures. The primary and secondary structures of the molecule and target protease selectivity are consistent with those of plasma-derived C1 esterase inhibitor.

• Each vial of conestat alfa contains 2100 IU of rhC1INH, 937 mg of sucrose, 83.3 mg of sodium citrate dihydrate and 1.0 mg of citric acid monohydrate. After reconstitution with 14 mL of sterile Water for Injection, each vial of conestat alfa contains 150 IU of rhC1INH per 1 mL in a 20 mM sodium citrate buffer with a pH of 6.8. conestat alfa does not contain preservatives and each vial is for single use only.

• conestat alfa is purified from the milk of transgenic rabbits. The rabbits are maintained in a closed colony that is controlled and routinely monitored for specific pathogens. The skimmed milk is screened for adventitious contaminants prior to further manufacture. The manufacturing process has been validated to demonstrate adequate capacity for removal and/or inactivation of viruses (Table 4). conestat alfa contains less than 0.002% of host-related impurities.

This image is provided by the National Library of Medicine.

Pharmacodynamics

• The complement component (protein) C4 is a substrate for activated C1. Patients with HAE have low levels of C4 in the circulation; conestat alfa shows a dose-dependent restoration of complement homeostasis of C4 in HAE patients. A dose of 50 IU/kg of conestat alfa increases plasma C1INH activity levels to greater than 0.7 IU/mL (the lower limit of normal) in HAE patients.

Pharmacokinetics

• The pharmacokinetics of conestat alfa was evaluated in a study of 12 asymptomatic HAE patients (dose ranged from 6.25 IU/kg to 100 IU/kg). Pharmacokinetics evaluation was performed by non-compartmental analysis, using functional C1INH levels. Following administration of conestat alfa (50 IU/kg) in asymptomatic HAE patients (Table 5), the mean Cmax was 1.2 IU/mL, and the elimination half-life was approximately 2.5 hours. The clearance of conestat alfa was nonlinear (clearance decreased with increasing dose) over the dose range of 25-100 IU/kg.

This image is provided by the National Library of Medicine.

• Studies have not been conducted to evaluate the PK of conestat alfa in special patient populations, identified by race, age (pediatric or geriatric), or the presence of renal or hepatic impairment.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

• No animal studies have been conducted to evaluate the effects of conestat alfa on carcinogenesis and mutagenesis. Fertility was not evaluated in animal studies.

Animal Toxicology and/or Pharmacology

• Single- and repeat-dose studies of up to 14 days in rats, dogs, and cynomolgus monkeys with daily doses of conestat alfa up to 80 times the human dose (50 IU/kg) were conducted. In a 14-day monkey toxicology study of intravenous doses up to 2000 IU/kg twice daily, increases in AST and ALP were observed at doses of 500 IU/kg and higher. No histopathological correlates were observed in the liver and the increases in liver enzymes were reversible. Histologic findings included changes in the size of thymic cortex and medulla, and microvacuoles in the epithelial cells lining the renal tubules. The renal tubular vacuolation was dose dependent, but was not accompanied by other histological changes in the kidney. This finding was only partially reversible at the highest dose level of 2000 IU/kg twice daily. It was concluded that the NOAEL of conestat alfa was 1000 IU/kg twice daily in this species. There were no adverse findings in a safety pharmacology study in dogs and a local tolerance study in rabbits. It is concluded that preclinical toxicology data for daily doses up to 40 times the proposed human dose of conestat alfa (50 IU/kg) do not indicate a safety concern for the use of conestat alfa in humans.

• Embryo-fetal studies have been conducted in rabbits and rats at a dose of conestat alfa 12.5 times the human dose of 50 IU/kg. In rats, no malformed fetuses were observed. In rabbits, an increase in the incidence of fetal cardiac vessel defects was observed (1.12% [2 cases] in the treatment group compared to 0.03% in historical controls). These defects are considered to be a chance finding, but a conestat alfa-related effect cannot be excluded.

Clinical Studies

• The safety and efficacy of conestat alfa for treatment of acute angioedema attacks in patients with HAE was established in Study 1, a double-blind, randomized, placebo-controlled trial (RCT) which included an open-label extension (OLE) phase; and supported by the results of 2 additional RCTs and 2 additional OLE studies.

Randomized, Controlled Trials

• The safety and efficacy of conestat alfa in the treatment of acute attacks in patients with hereditary angioedema were demonstrated in a placebo-controlled, double-blind, randomized study (Study 1). Supportive evidence of effectiveness is provided by two double-blind, randomized, placebo-controlled studies (Studies 2 and 3). Evidence for the efficacy of repeat treatment of HAE attacks is provided from the open-label extensions (OLE) of each of the three randomized studies.

• Study 1 was a randomized, double-blind, placebo-controlled trial that included an open-label extension (OLE) phase to assess the efficacy and safety of conestat alfa 50 IU/kg in the treatment of acute attacks in patients with HAE. Seventy-five (75) adults and adolescent patients were randomized (3:2) to receive conestat alfa 50 IU/kg (N = 44) or placebo (N = 31). Patients ranged in age from 17 to 69 years of age; 63% were female and 37% were male; 96% were Caucasian.

• The primary efficacy endpoint was the time to beginning of relief of symptoms, assessed using patient-reported responses to two questions from a Treatment Effect Questionnaire (TEQ). The TEQ required patients to assess the severity of their attack symptoms at each affected anatomic location, using a seven-point scale (“much worse” to “much better” [TEQ Question 1]), and whether their symptoms had begun to decrease notably since receiving the study medication (“yes” or “no” [TEQ Question 2]). To achieve the primary endpoint, a patient had to have a positive response to both questions along with persistence of improvement at the next assessment time (i.e., the same or better response).

• Rescue treatment with conestat alfa was available for patients who did not experience the beginning of relief at 4 hours after study drug administration, or earlier to patients who experienced life-threatening oropharyngeal-laryngeal angioedema symptoms. If a patient received a medication which could have impacted the efficacy evaluation or open-label conestat alfa as rescue medication, prior to achieving beginning of relief of symptoms, the time to beginning of relief of symptoms was censored at the last assessed time prior to medication use.
• In the RCT phase, the median time to beginning of relief of symptoms was statistically significantly shorter in patients treated with conestat alfa 50 IU/kg compared with patients treated with placebo as assessed by the TEQ;

This image is provided by the National Library of Medicine.

This image is provided by the National Library of Medicine.

• Among several planned subgroup analyses, descriptive statistics showed that in US patients a median time to beginning of relief of symptoms with persistence at the primary attack location (based on TEQ) was 98 minutes [95% CI: (45, 240); n=22] for those receiving conestat alfa and 90 minutes [95% CI: (50, -); n=16] for those receiving placebo. The hazard ratio for time to the beginning of relief of symptoms in this subpopulation was 1.20 [95% CI: 0.48 to 3.01] for patients receiving conestat alfa as compared with patients receiving placebo. Non-US patients receiving conestat alfa had a median time to beginning of relief of 90 minutes [95% CI: (63, 120); n=22] and non-US patients receiving placebo had a median time to beginning of relief of 334 minutes [95% CI: (150, -); n=15]. The hazard ratio for the non-US subgroup was 4.82 [95% CI: 1.58 to 14.72] for patients receiving conestat alfa compared to placebo.

• Examination of gender subgroups suggested a larger treatment effect in men than women. For women receiving conestat alfa, the median time to beginning of relief was 113 minutes [95% CI: (63, 151); n=28], and for women receiving placebo, the median time to beginning of relief was 105 minutes [95% CI: (60, 334); n=19]. The hazard ratio for women receiving conestat alfa versus placebo was 1.22 [95% CI: 0.60 to 2.48]. For men receiving conestat alfa, the median time to beginning of relief was 75 minutes [95% CI: (45, 210); n=16], and for men receiving placebo, the median time to beginning of relief was 480 minutes [95% CI: (150, -); n=12]. *The hazard ratio for men receiving conestat alfa versus placebo was 3.94 [95% CI: 1.23 to 12.68].

• No plausible biological explanations for the regional or gender subgroup effects were found. One possible explanation is a larger-than-expected placebo response among US women. None of the subgroup confidence intervals were adjusted for multiplicity.

• Because almost all of the patients were Caucasian and were between 18 and 65 years of age, race and age subgroup analyses were not considered meaningful.

• Among patients who achieved relief within 4 hours, there were 4 (27%) patients in the placebo group who had a relapse of their symptoms within 24 hours as compared with 1 (3%) in the conestat alfa group. The proportion of patients who received conestat alfa as rescue medication was greater in patients randomized to placebo (13 of 31 patients; 42%) than in patients randomized to conestat alfa (5 of 44 patients; 11%).

• The efficacy of conestat alfa 50 IU/kg for different anatomical locations of HAE attacks is summarized in Table 7.

This image is provided by the National Library of Medicine.

• Life-threatening laryngeal attacks were excluded from the randomized-controlled phase of Study 1

• In the OLE phase of Study 1, patients were treated with open-label conestat alfa 50 IU/kg for repeated attacks of HAE. Forty-four patients who completed the RCT phase were enrolled into the OLE phase where they were treated for a total of 170 attacks. In this phase, the median time to beginning of relief of symptoms was 75 minutes (95% CI: 64, 90), consistent with the results of the RCT phase of the study (Table 6). Results were also comparable across attacks, suggesting that the efficacy of conestat alfa 50 IU/kg was maintained over repeated attacks of HAE. In the OLE phase of Study 1, 5/170 (3%) attacks received a second dose of conestat alfa 50 IU/kg.

• In Study 2 (North American RCT), patients were randomized to receive a single administration of either conestat alfa 50 IU/kg (N=12), conestat alfa 100 IU/kg (N=13) or placebo (N=13). Patients ranged in age from 17 to 66 years of age; 74% were female and 26% were male; and 92% were Caucasian.

• In Study 3 (European RCT), patients were randomized to receive a single administration of either conestat alfa 100 IU/kg (N=16) or placebo (N=16). Patients ranged in age from 17 to 71 years of age: 53% were female and 47% were male; and 100% were Caucasian.

• Patients scored their symptoms using a visual analog scale (VAS) ranging from 0-100 mm. A VAS decrease of > 20 mm compared with baseline with persistence of the improvement at two consecutive time points was considered the onset of relief in Studies 2 and 3.

• In both Study 2 and 3, the efficacy of conestat alfa in the treatment of acute angioedema attacks was demonstrated by significantly shorter times to beginning of relief of symptoms based on the VAS (Figure 2).

This image is provided by the National Library of Medicine.

• In open-label extension studies of Study 2 and 3, 119 patients were treated with conestat alfa for a total of 362 acute angioedema attacks. As observed in Study 1, the efficacy of conestat alfa was maintained for repeat attacks.

How Supplied

• conestat alfa is supplied in single-use 25 mL glass vials with a stopper (siliconized chlorobutyl rubber) and a flip-off seal (aluminum and colored plastic).
• Each carton contains one single-use vial.
• Each vial contains 2100 IU rhC1INH lyophilized powder for reconstitution for injection.
• Store in the original package in order to protect from light.
• Shelf life: 48 months when stored at 2°C to 25°C (36°F to 77°F).
• Do not freeze.
• Each vial of conestat alfa should be reconstituted with 14 mL Water for Injection (not supplied). The reconstituted solution contains 150 IU/mL rhC1INH and is clear and colorless.
• Each vial of conestat alfa is for single use only. conestat alfa contains no preservative. Any product that has been reconstituted should be used immediately, or within 8 hours stored at 2°C to 8°C (36°F to 46°F). Discard partially used vials after treatment

Storage

There is limited information regarding Conestat alfa Storage in the drug label.

Images

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Patient Counseling Information

• Advise the patient to read the FDA-Approved patient labeling (Product Information and Instructions for Use).
• Patients being treated with conestat alfashould receive the following information and instructions. This information is intended to aid the patient in the safe and effective use of conestat alfa.
• Advise female patients to notify their physician if they are pregnant or intend to become pregnant during the treatment of acute attacks of HAE with conestat alfa.
• Advise patients to notify their physician if they are breastfeeding or plan to breastfeed.
• Inform patients of the risks and benefits of conestat alfa before prescribing or administering it to the patient.
• Advise patients to immediately report:
• Signs and symptoms of allergic hypersensitivity reactions, such as hives, urticaria, tightness of the chest, wheezing, hypotension and/or anaphylaxis experienced during or after injection of conestat alfa

Precautions with Alcohol

• Alcohol-Conestat alfa interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

• Ruconest

Look-Alike Drug Names

There is limited information regarding Conestat alfa Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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