Human C1 Esterase Inhibitor

Kallikrein Inhibitors

Hereditary Angioedemas

<section class="Section" data-sectioncode="34089-3"><a name="S11"></a><a name="section-10"></a><p></p><h1>11 DESCRIPTION</h1><p class="First">HAEGARDA is a human plasma-derived, purified, pasteurized, lyophilized concentrate of C1-INH to be reconstituted for S.C. administration. HAEGARDA is prepared from large pools of human plasma from U.S. donors. The potency of C1-INH is expressed in International Units (IU), which is related to the current WHO Standard for C1-INH products.</p><p>Reconstituted HAEGARDA has a concentration of 500 IU/mL C1-INH, 65 mg/mL total protein, 10 mg/mL glycine, 8.5 mg/mL sodium chloride and 2.7 mg/mL sodium citrate.</p><div class="Section" data-sectioncode="42229-5"><a name="section-10.1"></a><p></p><p class="First"><span class="Underline">C1 Esterase Inhibitor</span></p><p>C1-INH is a soluble, single-chain highly glycosylated protein containing 478 amino acid residues which belongs to the serine protease inhibitor (serpin) family.</p><p>All plasma used in the manufacturing of C1-INH is obtained from U.S. donors and is tested using serological assays for hepatitis B surface antigen and antibodies to HIV-1/2 and HCV. Additionally, the plasma is tested with Nucleic Acid Testing (NAT) for HBV, HCV, HIV-1 and HAV and found to be non-reactive (negative). The plasma is also tested by NAT for Human Parvovirus B19. Only plasma that has passed virus screening is used for production, and the limit for Parvovirus B19 in the fractionation pool is set not to exceed 10<span class="Sup">4</span> IU of Parvovirus B19 DNA per mL.</p><p>The manufacturing process for HAEGARDA includes multiple steps that reduce the risk of virus transmission. The virus inactivation/reduction capacity consists of three steps:</p><ul class="Disc"><li>Pasteurization in aqueous solution at 60°C for 10 hours</li><li>Hydrophobic interaction chromatography</li><li>Virus filtration (also called nanofiltration) by two filters, 20 nm and 15 nm, in series. </li></ul><p>Viral inactivation and reduction were evaluated in a series of in vitro spiking experiments. The total mean cumulative virus inactivation/reduction is shown in Table 2.</p><table width="100%"><caption><span>Table 2. Mean Virus Inactivation/Reductions in HAEGARDA</span></caption><col align="left" valign="middle" width="17%"/><col align="center" valign="middle" width="17%"/><col align="center" valign="middle" width="28%"/><col align="center" valign="middle" width="19%"/><col align="center" valign="middle" width="19%"/><thead><tr class="First Last"><th align="center" class="Lrule Rrule" valign="middle">Virus Studied</th><th align="center" class="Rrule">Pasteurization<br/> [log<span class="Sub">10</span>]</th><th align="center" class="Rrule">Hydrophobic Interaction Chromatography<br/>[log<span class="Sub">10</span>]</th><th align="center" class="Rrule">Virus Filtration<br/>[log<span class="Sub">10</span>]</th><th align="center" class="Rrule">Total Cumulative [log<span class="Sub">10</span>]</th></tr></thead><tfoot><tr class="First"><td align="left" colspan="5">HIV-1, Human immunodeficiency virus type 1, a model for HIV-1 and HIV-2</td></tr><tr><td align="left" colspan="5">BVDV, Bovine viral diarrhea virus, a model for HCV</td></tr><tr><td align="left" colspan="5">PRV, Pseudorabies virus, a model for large enveloped DNA viruses</td></tr><tr><td align="left" colspan="5">WNV, West Nile virus</td></tr><tr><td align="left" colspan="5">HAV, Hepatitis A virus</td></tr><tr><td align="left" colspan="5">CPV, Canine parvovirus</td></tr><tr><td align="left" colspan="5">B19V, Human Parvovirus</td></tr><tr><td align="left" colspan="5">B19ND, Not determined</td></tr><tr class="Last"><td align="left" colspan="5">NA, Not applicable</td></tr></tfoot><tbody><tr class="Botrule First"><td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">Enveloped Viruses</span></td></tr><tr class="Botrule"><td align="left" class="Lrule Rrule">HIV-1</td><td align="center" class="Rrule">≥6.6</td><td align="center" class="Rrule">≥4.5</td><td align="center" class="Rrule">≥5.1</td><td align="center" class="Rrule">≥16.2</td></tr><tr class="Botrule"><td align="left" class="Lrule Rrule">BVDV</td><td align="center" class="Rrule">≥9.2</td><td align="center" class="Rrule">≥4.7</td><td align="center" class="Rrule">≥5.3</td><td align="center" class="Rrule">≥19.2</td></tr><tr class="Botrule"><td align="left" class="Lrule Rrule">PRV</td><td align="center" class="Rrule">6.3</td><td align="center" class="Rrule">≥6.5</td><td align="center" class="Rrule">≥7.1</td><td align="center" class="Rrule">≥19.9</td></tr><tr class="Botrule"><td align="left" class="Lrule Rrule">WNV</td><td align="center" class="Rrule">≥7.0</td><td align="center" class="Rrule">ND</td><td align="center" class="Rrule">≥8.0</td><td align="center" class="Rrule">≥15.0</td></tr><tr class="Botrule"><td align="left" class="Lrule Rrule" colspan="5"><span class="Bold">Non-Enveloped Viruses</span></td></tr><tr class="Botrule"><td align="left" class="Lrule Rrule">HAV</td><td align="center" class="Rrule">≥6.4</td><td align="center" class="Rrule">2.8</td><td align="center" class="Rrule">≥5.3</td><td align="center" class="Rrule">≥14.5</td></tr><tr class="Botrule"><td align="left" class="Lrule Rrule">CPV</td><td align="center" class="Rrule">1.4</td><td align="center" class="Rrule">3.9</td><td align="center" class="Rrule">7.1</td><td align="center" class="Rrule">12.4</td></tr><tr class="Last"><td align="left" class="Lrule Rrule">B19V</td><td align="center" class="Rrule">3.9</td><td align="center" class="Rrule">ND</td><td align="center" class="Rrule">ND</td><td align="center" class="Rrule">NA</td></tr></tbody></table></div></section>

HAEGARDA

C1 esterase inhibitor

C1 esterase inhibitor (human)

C1 esterase inhibitor (human) 2000 UNT Injection

C1 esterase inhibitor (human) 2000 UNT Injection [Haegarda]

C1 esterase inhibitor (human) 3000 UNT Injection

C1 esterase inhibitor (human) 3000 UNT Injection [Haegarda]

Haegarda

Cytochrome P450 2D6 Inhibitors

Cytochrome P450 3A4 Inhibitors

P-Glycoprotein Inhibitors

Plasma Kallikrein Inhibitor

<section class="Section" data-sectioncode="34089-3"><a name="S11"></a><a name="section-9"></a><p></p><h1>11 DESCRIPTION</h1><p class="First">ORLADEYO (berotralstat) capsules is a plasma kallikrein inhibitor. Berotralstat is presented as the dihydrochloride salt with the chemical name 1-[3-(aminomethyl)phenyl]-<span class="Italics">N</span>-(5-{(<span class="Italics">R</span>)-(3-cyanophenyl)[(cyclopropylmethyl)amino]methyl}-2-fluorophenyl)-3-(trifluoromethyl)-1<span class="Italics">H</span>-pyrazole-5-carboxamide dihydrochloride. The chemical structure is:</p><div class="Figure"><img alt="Chemical Structure" src="orladeyo-01.jpg"/></div><p>Berotralstat dihydrochloride is a white to off-white powder that is soluble in water at pH ≤4. The molecular formula is C<span class="Sub">30</span>H<span class="Sub">26</span>F<span class="Sub">4</span>N<span class="Sub">6</span>O ∙ 2HCl and the molecular weight is 635.49 (dihydrochloride).</p><p>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.</p></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]

Haegarda is a synthetic version of a blood protein that regulates swelling in the body. Individuals with Hereditary Angioedema (HAE) lack sufficient levels of this protein, leading to swelling episodes and symptoms like digestive issues and breathing difficulties.

Haegarda is an injectable medication designed to proactively prevent swelling and painful attacks in patients aged 6 and older with Hereditary Angioedema.

It's important to note that Haegarda is not intended for the treatment of acute HAE attacks. If you experience an acute HAE attack, please initiate personalized treatment as advised by your healthcare provider.

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FAQs: Hereditary Angioedema (HAE)

Instructions For Use: Hereditary Angioedema (HAE)

Women and Hereditary Angioedema Brochure

Managing HAE Checklist

Doctor Discussion Guide

Haegarda Compliance Brochure

Helpful Tips for Safe Travel

Travel Medical Letter

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.

Haegarda®(C1 esterase inhibitor (human))	Orladeyo®(berotralstat)

Prescription Only Haegarda is a synthetic version of a blood protein that regulates swelling in the body. Individuals with Hereditary Angioedema (HAE) lack sufficient levels of this protein,...	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
Subcutaneous . Learn more.	Oral. Learn more.
Dosing
Administer 60 International Units per kg body weight twice weekly (every 3 or 4 days).. Learn more.	One capsule (150 mg) taken orally once daily with food.. Learn more.
Latin Shorthand
Administer 60 IU/kg BW BID (q3-4d).. 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
Adverse reactions occurring in more than 4% of subjects treated with HAEGARDA were injection site reactions, hypersensitivity, nasopharyngitis and dizziness.. 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 it safe to use HAEGARDA during pregnancy? There are no prospective clinical data from HAEGARDA use in pregnant women. However, limited retrospective data suggest that C1-INH treatment during pregnancy did not lead to adverse events. The estimated background risk of birth defects and miscarriage in the general U.S. population is 2-4% and 15-20%, respectively. 2. What is known about HAEGARDA use during lactation? There is no information available about the presence of HAEGARDA in human milk, its impact on breastfed infants, or its effects on milk production. The decision to breastfeed should consider the benefits of breastfeeding and the mother's clinical need for HAEGARDA, while also evaluating potential adverse effects on the breastfed infant. 3. Has HAEGARDA been tested in pediatric patients? Yes, the safety and effectiveness of HAEGARDA were evaluated in a subgroup of patients aged 8 to <17 years in clinical trials, and the results were consistent with overall study results. 4. Is HAEGARDA suitable for use in geriatric patients? Clinical studies of HAEGARDA did not include sufficient numbers of subjects aged 65 and over to determine if they respond differently from younger subjects. However, reported clinical experience has not identified differences in responses between the elderly and younger patients. Dosing for elderly patients should be cautious and typically start at the lower end of the dosing range, considering factors like decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapies.

Haegarda® Alternatives