Human C1 Esterase Inhibitor

Kallikrein Inhibitors

Hereditary Angioedemas

<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">BERINERT is a human plasma-derived, purified, pasteurized, lyophilized concentrate of C1 esterase inhibitor to be reconstituted for intravenous administration. BERINERT is prepared from large pools of human plasma from US donors. The potency of C1 esterase inhibitor is expressed in International Units (IU), which is related to the current WHO Standard for C1 esterase inhibitor products.</p><p>C1 esterase inhibitor is a soluble, single-chain glycoprotein containing 478 amino acid residues organized into three beta-sheets and eight or nine alpha-helices.<span class="Sup">4</span> The heavily glycosylated molecule has an apparent molecular weight of 105 kD, of which the carbohydrate chains comprise 26% to 35%.<span class="Sup">5</span></p><p>Each 500 IU vial of reconstituted BERINERT contains 400-625 IU C1 esterase inhibitor, 50 to 80 mg total protein, 85 to 115 mg glycine, 70 to 100 mg sodium chloride, and 25 to 35 mg sodium citrate.</p><p>All plasma used in the manufacture of BERINERT is obtained from US 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). In addition, 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 BERINERT 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>This was evaluated in a series of in vitro spiking experiments. The total mean cumulative virus inactivation/reduction is shown in Table 2.</p><table width="90%"><caption><span>Table 2. Mean Virus Inactivation/Reductions in BERINERT</span></caption><col align="left" valign="middle" width="18%"/><col align="center" valign="middle" width="18%"/><col align="center" valign="middle" width="28%"/><col align="center" valign="middle" width="18%"/><col align="center" valign="middle" width="18%"/><thead><tr class="First Last"><th align="center" class="Lrule Rrule">Virus Studied</th><th align="center" class="Rrule" valign="bottom">Pasteurization<br/>[log<span class="Sub">10</span>]</th><th align="center" class="Rrule" valign="bottom">Hydrophobic Interaction Chromatography<br/>[log<span class="Sub">10</span>]</th><th align="center" class="Rrule" valign="bottom">Virus Filtration<br/>[log<span class="Sub">10</span>]</th><th align="center" class="Rrule" valign="bottom">Total Cumulative<br/>[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 B19</td></tr><tr><td align="left" colspan="5">ND, 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></section>

Berinert

C1 esterase inhibitor

C1 esterase inhibitor (human)

C1 esterase inhibitor (human) 500 UNT Injection

C1 esterase inhibitor (human) 500 UNT Injection [Berinert]

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]

Berinert is a synthetic version of a protein naturally found in the bloodstream, which plays a role in regulating swelling within the body. Individuals with hereditary angioedema lack an adequate amount of this protein, which can lead to episodes of swelling and accompanying symptoms like digestive issues or breathing difficulties.

Berinert is prescribed for individuals with hereditary angioedema.

It is employed to manage acute angioedema attacks.

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FAQs: HAE

Instructions For Use: HAE

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.

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

Prescription Only Berinert is a synthetic version of a protein naturally found in the bloodstream, which plays a role in regulating swelling within the body. Individuals with hereditary angioedema...	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
Administer 20 International Units per kg body weight.. Learn more.	One capsule (150 mg) taken orally once daily with food.. Learn more.
Latin Shorthand
Administer 20 IU/kg BW.. 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 most serious adverse reaction reported in subjects who received BERINERT was an increase in the severity of pain associated with HAE. •The most common adverse reaction reported in greater than 4% of the subjects and greater than placebo among subjects who received BERINERT in the placebo-controlled clinical trial was dysgeusia.. 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

Berinert® Alternatives