<section class="Section" data-sectioncode="34089-3"><a name="LINK_adf498f2-321a-4ed9-a8a6-b3f986feb2b0"></a><a name="section-8"></a><h1>11 DESCRIPTION</h1>RUCONEST is a recombinant analogue of human complement component 1 esterase inhibitor for intravenous injection. RUCONEST 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 U of rhC1INH activity is defined as the equivalent of C1 esterase inhibiting activity present in 1 mL of pooled normal plasma.RUCONEST 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 RUCONEST contains 2100 U 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 RUCONEST contains 150 U of rhC1INH per 1 mL in a 20 mM sodium citrate buffer with a pH of 6.8. RUCONEST does not contain preservatives and each vial is for single use only. RUCONEST 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 ( <a href="#_Ref439236544">Table 4</a>).  RUCONEST contains less than 0.002% of host-related impurities. <a name="_Ref439236544"></a><table cellpadding="0pt" cellspacing="0pt" width="55%"><caption>Table 4. Viral reduction capacity of the rhC1INH manufacturing process</caption><col width="16%"/><col width="10%"/><col width="10%"/><col width="10%"/><col width="9%"/><col width="8%"/><tfoot><tr class="First Last"><td align="left" class="Botrule" colspan="6" valign="top">a MLV: Murine leukemia virus; REO-3: Reovirus type 3; ORF: Scab-mouth ORF virus; FCV: Feline calicivirus; PPV: Porcine parvovirus; b SP BB: SP Sepharose BB; SD: Solvent/detergent; Q HP: Q Sepharose HP; Zn FF: Zinc Chelating Sepharose FF; c Not added to the total reduction factor since independence of clearance mechanism has not been experimentally verified; d Not applicable since indicated model virus is not enveloped; e Not tested because SD chemicals are present in the starting material. </td></tr></tfoot><tbody class="Headless"><tr class="First"><td class="Botrule Lrule Rrule Toprule" valign="top"></td><td class="Botrule Lrule Rrule Toprule" colspan="5" valign="top">Virus Reduction Factor (Log 10) </td></tr><tr><td class="Botrule Lrule Rrule" valign="middle">Step</td><td class="Botrule Lrule Rrule" valign="middle">MLV a</td><td class="Botrule Lrule Rrule" valign="middle">REO 3</td><td class="Botrule Lrule Rrule" valign="middle">ORF</td><td class="Botrule Lrule Rrule" valign="middle">FCV</td><td class="Botrule Lrule Rrule" valign="middle">PPV</td></tr><tr><td class="Botrule Lrule Rrule" valign="middle">SP BB chromatography b</td><td class="Botrule Lrule Rrule" valign="top">1.8</td><td class="Botrule Lrule Rrule" valign="top">2.2 c</td><td class="Botrule Lrule Rrule" valign="top">1.5 c</td><td class="Botrule Lrule Rrule" valign="top">2.3</td><td class="Botrule Lrule Rrule" valign="top">1.5 b</td></tr><tr><td class="Botrule Lrule Rrule" valign="middle">SD incubation b</td><td class="Botrule Lrule Rrule" valign="top">≥ 5.8</td><td class="Botrule Lrule Rrule" valign="top">NA d</td><td class="Botrule Lrule Rrule" valign="top">3.7</td><td class="Botrule Lrule Rrule" valign="top">NA</td><td class="Botrule Lrule Rrule" valign="top">NA</td></tr><tr><td class="Botrule Lrule Rrule" valign="middle">Q HP chromatography b</td><td class="Botrule Lrule Rrule" valign="top">NT e</td><td class="Botrule Lrule Rrule" valign="top">4.8</td><td class="Botrule Lrule Rrule" valign="top">NT</td><td class="Botrule Lrule Rrule" valign="top">0.8 c</td><td class="Botrule Lrule Rrule" valign="top">2.2</td></tr><tr><td class="Botrule Lrule Rrule" valign="middle">Zn FF chromatography b</td><td class="Botrule Lrule Rrule" valign="top">1.1 c</td><td class="Botrule Lrule Rrule" valign="top">3.2 c</td><td class="Botrule Lrule Rrule" valign="top">3.3</td><td class="Botrule Lrule Rrule" valign="top">1.9 c</td><td class="Botrule Lrule Rrule" valign="top">0.4 c</td></tr><tr><td class="Botrule Lrule Rrule" valign="middle">Nanofiltration</td><td class="Botrule Lrule Rrule" valign="top">≥ 5.5</td><td class="Botrule Lrule Rrule" valign="top">≥ 6.5</td><td class="Botrule Lrule Rrule" valign="top">≥ 5.8</td><td class="Botrule Lrule Rrule" valign="top">≥ 6.9</td><td class="Botrule Lrule Rrule" valign="top">5.8</td></tr><tr class="Last"><td class="Botrule Lrule Rrule" valign="middle">Total reduction factor</td><td class="Botrule Lrule Rrule" valign="top">≥ 13.1</td><td class="Botrule Lrule Rrule" valign="top">≥ 11.3</td><td class="Botrule Lrule Rrule" valign="top">≥ 12.8</td><td class="Botrule Lrule Rrule" valign="top">≥ 9.2</td><td class="Botrule Lrule Rrule" valign="top">8.0</td></tr></tbody></table></section>

Ruconest

C1 esterase inhibitor

C1 esterase inhibitor (recombinant)

C1 esterase inhibitor (recombinant) 2100 UNT Injection

C1 esterase inhibitor (recombinant) 2100 UNT Injection [Ruconest]

Cytochrome P450 2D6 Inhibitors

Cytochrome P450 3A4 Inhibitors

Kallikrein Inhibitors

P-Glycoprotein Inhibitors

Plasma Kallikrein Inhibitor

<section class="Section" data-sectioncode="34089-3"><a name="S11"></a><a name="section-9"></a><h1>11 DESCRIPTION</h1>ORLADEYO (berotralstat) capsules is a plasma kallikrein inhibitor. Berotralstat is presented as the dihydrochloride salt with the chemical name 1-[3-(aminomethyl)phenyl]-N-(5-{(R)-(3-cyanophenyl)[(cyclopropylmethyl)amino]methyl}-2-fluorophenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide dihydrochloride. The chemical structure is:<div class="Figure"><img alt="Chemical Structure" src="orladeyo-01.jpg"/></div>Berotralstat dihydrochloride is a white to off-white powder that is soluble in water at pH ≤4. The molecular formula is C30H26F4N6O ∙ 2HCl and the molecular weight is 635.49 (dihydrochloride).ORLADEYO is supplied as 150 mg (equivalent to 169.4 mg berotralstat dihydrochloride) and 110 mg (equivalent to 124.3 mg berotralstat dihydrochloride) hard gelatin capsules for oral administration. Each capsule contains the active ingredient berotralstat dihydrochloride and the inactive ingredients colloidal silicon dioxide, crospovidone, magnesium stearate, and pregelatinized starch.</section>

Orladeyo

berotralstat

berotralstat 110 MG Oral Capsule

berotralstat 110 MG Oral Capsule [Orladeyo]

berotralstat 150 MG Oral Capsule

berotralstat 150 MG Oral Capsule [Orladeyo]

Ruconest is a synthetic version of the naturally occurring c1 esterase inhibitor protein in the bloodstream, which plays a crucial role in regulating swelling in the body. Individuals with Hereditary Angioedema lack an adequate amount of this protein, leading to episodes of swelling and associated symptoms like digestive issues and breathing difficulties.

Ruconest is an injectable medication designed to treat acute angioedema attacks in adult and adolescent patients with Hereditary Angioedema.

Ruconest is intended for use in individuals who are at least 13 years old.

Report Adverse Event

Prescribing Information

Medication Guide

Pharmacy List [mentioned at the top of form]

Billing and Coding Guide

Coverage Authorization Request 

Coverage Authorization Appeals

Letter of Medical Necessity - English

Letter of Medical Necessity - Spanish

Ruconest Enrollment Form 

Ruconest Enrollment Form - Spanish 

Enroll in Patient Savings Program

Starter Rx - Bridge Program 

Patient Assistance Program 

Other HCP Resources: Video 

About Ruconest 

HAE and Me App 

Patient Resources: Videos

Ruconest Solutions Support Program 

Reimbursement Form [To seek reimbursement for out-of-pocket medical and travel expenses pertaining to Ruconest]

Patient Brochure

Doctor Discussion Guide 

Doctor Discussion Guide - Spanish

Instructions For Use: Hereditary Angioedema

Instructions For Use (Spanish): Hereditary Angioedema

Orladeyo is prescribed to prevent hereditary angioedema (HAE) attacks in individuals aged 12 and above.

It should not be used to treat an ongoing HAE attack.

The safety and effectiveness of Orladeyo in children under 12 years of age are currently unknown.

Ruconest®(C1 esterase inhibitor (recombinant))	Orladeyo®(berotralstat)

Prescription Only Ruconest is a synthetic version of the naturally occurring c1 esterase inhibitor protein in the bloodstream, which plays a crucial role in regulating swelling in the body....	Prescription Only Orladeyo is prescribed to prevent hereditary angioedema (HAE) attacks in individuals aged 12 and above. It should not be used to treat an ongoing HAE attack. The safety and...
Dosage & Administration
Administration
Intravenous. Learn more.	Oral. Learn more.
Dosing
Weight <84 kg: 50 U per kg. Weight ≥84 kg: 4200 U (2 vials).. Learn more.	One capsule (150 mg) taken orally once daily with food.. Learn more.
Latin Shorthand
Weight <84 kg: 50 U/kg. Weight ≥84 kg: 4200 U (2 vials).. Learn more.	1 capsule po qd w/food.. Learn more.
Financial Assistance
Out-Of-Pocket Costs With Copay Card
Learn more.	$0. Learn more.
Annual Cap
Learn more.	Learn more.
Assistance Expiration
Learn more.	Calendar year. Learn more.
Generics
No lower-cost generic available	No lower-cost generic available
Physician Advisory
Adverse Reactions
The serious adverse reaction reported in clinical trials was anaphylactic reaction. The common adverse reactions (≥ 2%) reported in clinical trials were headache, nausea, and diarrhea.. Learn more.	Most common adverse reactions (≥10%) are abdominal pain, vomiting, diarrhea, back pain, and gastroesophageal reflux disease.. Learn more.
Mechanism of Actions (MoA)
Drugs used in Hereditary Angioedema. Learn more.	Drugs used in Hereditary Angioedema. Learn more.
Special Populations
1. Is RUCONEST safe to use during pregnancy? There are no adequate and well-controlled studies of RUCONEST in pregnant women. Limited postmarketing data suggest no adverse effects in pregnant women treated with RUCONEST. A retrospective case collection study involving 14 pregnant women who received RUCONEST did not report adverse events related to RUCONEST treatment, and all women delivered healthy babies. However, the data's ability to definitively establish absence of risk is limited due to the study's small sample size and non-randomized design. 2. What do we know about RUCONEST use during lactation? There is no available data on the presence of RUCONEST in human milk, its effects on breastfed infants, or its impact on milk production. When considering the use of RUCONEST, the developmental and health benefits of breastfeeding should be balanced with the mother's clinical need, while also assessing potential adverse effects on the breastfed child from RUCONEST or the maternal condition. 3. Has RUCONEST been tested in pediatric patients? Yes, the safety and efficacy of RUCONEST were evaluated in 17 adolescent patients aged 13-17 years who were treated for HAE attacks. Some adverse reactions were observed in these patients, with the most common being abdominal pain, headache, and oropharyngeal pain. However, no serious adverse reactions were reported. 4. Is RUCONEST suitable for use in geriatric patients? Clinical studies of RUCONEST included seven patients older than 65 years, but the number of patients in this age group was insufficient to determine whether they respond differently from younger patients.

Ruconest® Alternatives