ישראל - אנגלית - Ministry of Health

bayer israel ltd - riociguat - film coated tablets - riociguat 1 mg - riociguat - chronic thromboembolic pulmonary hypertension (cteph) adempas is indicated for the treatment of adult patients with who functional class (fc) ii to iii with • inoperable cteph, • persistent or recurrent cteph after surgical treatment, to improve exercise capacity. pulmonary arterial hypertension (pah)adempas, as monotherapy or in combination with endothelin receptor antagonists, is indicated for the treatment of adult patients with pulmonary arterial hypertension (pah) with who functional class (fc) ii to iii to improve exercise capacity.efficacy has been shown in a pah population including aetiologies of idiopathic or heritable pah or pah associated with connective tissue disease.

ישראל - אנגלית - Ministry of Health

bayer israel ltd - riociguat - film coated tablets - riociguat 1.5 mg - riociguat - chronic thromboembolic pulmonary hypertension (cteph) adempas is indicated for the treatment of adult patients with who functional class (fc) ii to iii with • inoperable cteph, • persistent or recurrent cteph after surgical treatment, to improve exercise capacity. pulmonary arterial hypertension (pah)adempas, as monotherapy or in combination with endothelin receptor antagonists, is indicated for the treatment of adult patients with pulmonary arterial hypertension (pah) with who functional class (fc) ii to iii to improve exercise capacity.efficacy has been shown in a pah population including aetiologies of idiopathic or heritable pah or pah associated with connective tissue disease.

ישראל - אנגלית - Ministry of Health

bayer israel ltd - riociguat - film coated tablets - riociguat 1.5 mg - riociguat - chronic thromboembolic pulmonary hypertension (cteph) adempas is indicated for the treatment of adult patients with who functional class (fc) ii to iii with • inoperable cteph, • persistent or recurrent cteph after surgical treatment, to improve exercise capacity. pulmonary arterial hypertension (pah)adempas, as monotherapy or in combination with endothelin receptor antagonists, is indicated for the treatment of adult patients with pulmonary arterial hypertension (pah) with who functional class (fc) ii to iii to improve exercise capacity.efficacy has been shown in a pah population including aetiologies of idiopathic or heritable pah or pah associated with connective tissue disease.

ישראל - אנגלית - Ministry of Health

bayer israel ltd - riociguat - film coated tablets - riociguat 2 mg - riociguat - chronic thromboembolic pulmonary hypertension (cteph) adempas is indicated for the treatment of adult patients with who functional class (fc) ii to iii with • inoperable cteph, • persistent or recurrent cteph after surgical treatment, to improve exercise capacity. pulmonary arterial hypertension (pah)adempas, as monotherapy or in combination with endothelin receptor antagonists, is indicated for the treatment of adult patients with pulmonary arterial hypertension (pah) with who functional class (fc) ii to iii to improve exercise capacity.efficacy has been shown in a pah population including aetiologies of idiopathic or heritable pah or pah associated with connective tissue disease.

ישראל - אנגלית - Ministry of Health

bayer israel ltd - riociguat - film coated tablets - riociguat 2 mg - riociguat - chronic thromboembolic pulmonary hypertension (cteph) adempas is indicated for the treatment of adult patients with who functional class (fc) ii to iii with • inoperable cteph, • persistent or recurrent cteph after surgical treatment, to improve exercise capacity. pulmonary arterial hypertension (pah)adempas, as monotherapy or in combination with endothelin receptor antagonists, is indicated for the treatment of adult patients with pulmonary arterial hypertension (pah) with who functional class (fc) ii to iii to improve exercise capacity.efficacy has been shown in a pah population including aetiologies of idiopathic or heritable pah or pah associated with connective tissue disease.

ישראל - אנגלית - Ministry of Health

bayer israel ltd - riociguat - film coated tablets - riociguat 2.5 mg - riociguat - chronic thromboembolic pulmonary hypertension (cteph) adempas is indicated for the treatment of adult patients with who functional class (fc) ii to iii with • inoperable cteph, • persistent or recurrent cteph after surgical treatment, to improve exercise capacity. pulmonary arterial hypertension (pah)adempas, as monotherapy or in combination with endothelin receptor antagonists, is indicated for the treatment of adult patients with pulmonary arterial hypertension (pah) with who functional class (fc) ii to iii to improve exercise capacity.efficacy has been shown in a pah population including aetiologies of idiopathic or heritable pah or pah associated with connective tissue disease.

ישראל - אנגלית - Ministry of Health

bayer israel ltd - riociguat - film coated tablets - riociguat 2.5 mg - riociguat - chronic thromboembolic pulmonary hypertension (cteph) adempas is indicated for the treatment of adult patients with who functional class (fc) ii to iii with • inoperable cteph, • persistent or recurrent cteph after surgical treatment, to improve exercise capacity. pulmonary arterial hypertension (pah)adempas, as monotherapy or in combination with endothelin receptor antagonists, is indicated for the treatment of adult patients with pulmonary arterial hypertension (pah) with who functional class (fc) ii to iii to improve exercise capacity.efficacy has been shown in a pah population including aetiologies of idiopathic or heritable pah or pah associated with connective tissue disease.

אוסטרליה - אנגלית - Department of Health (Therapeutic Goods Administration)

sanofi-aventis australia pty ltd - dexamethasone, quantity: 0.5 mg/ml; framycetin sulfate, quantity: 5 mg/ml; gramicidin, quantity: 0.05 mg/ml - ear drops - excipient ingredients: phenethyl alcohol; polysorbate 80; citric acid monohydrate; sodium citrate dihydrate; lithium chloride; purified water; industrial methylated spirit; hydrochloric acid; sodium hydroxide - indications as at 5 october 2000: inflammatory and allergic conditions of the ear, e.g. otitis externa. eczema of the auditory meatus is often present and causes inflammation, exudation and pruritus, which are all rapidly relieved by dexamethasone. infection,often secondary to scratching, is generally due to staphylococci, e. coli, pseudomonas and proteus spp. which respond rapidly to framycetin.

ארצות הברית - אנגלית - NLM (National Library of Medicine)

takeda pharmaceuticals america, inc. - lanadelumab (unii: 2372v1tkxk) (lanadelumab - unii:2372v1tkxk) - takhzyro® is indicated for prophylaxis to prevent attacks of hereditary angioedema (hae) in adult and pediatric patients aged 2 years and older. none. risk summary there are no available data on takhzyro use in pregnant women to inform any drug associated risks. monoclonal antibodies such as lanadelumab-flyo are transported across the placenta during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy. an enhanced pre-and postnatal development (eppnd) study conducted in pregnant monkeys at doses resulting in exposures of up to 33 times the exposure achieved (on an auc basis) at the maximum recommended human dose (mrhd) revealed no evidence of harm to the developing fetus. the background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. 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 animal data in the eppnd study, pregnant cynomolgus monkeys were administered lanadelumab-flyo once weekly at subcutaneous doses resulting in up to 33 times the exposure at the mrhd (on an auc basis with maternal subcutaneous doses up to 50 mg/kg/week) from gestation day 20, at the beginning of organogenesis, through to parturition. there were no lanadelumab-flyo-related effects on maintenance of pregnancy or parturition. maternal lanadelumab-flyo treatment had no effects on embryo-fetal development, survival, growth, or postnatal development of offspring through 3 months of age. lanadelumab-flyo crossed the placenta in monkeys. offspring were exposed to lanadelumab-flyo at approximately 50% of the maternal plasma concentration out to postnatal day 21 (pnd 21). lanadelumab-flyo concentrations were approximately equivalent in maternal and offspring plasma at pnd 90. risk summary there are no data on the presence of lanadelumab-flyo in human milk, its effects on the breastfed infant, or its effects on milk production. lanadelumab-flyo was detected in the milk of lactating cynomolgus monkeys at approximately 0.2% of the maternal plasma concentration. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for takhzyro and any potential adverse effects on the breastfed infant from takhzyro or from the underlying maternal condition. data animal data available pharmacokinetic data in cynomolgus monkeys have shown excretion of lanadelumab-flyo in milk at approximately 0.2% of the maternal plasma level. the safety and effectiveness of takhzyro for prophylaxis to prevent attacks of hereditary angioedema (hae) have been established in pediatric patients 2 years of age and older. use of takhzyro for this indication in patients 12 years of age and older was supported by a subgroup analysis by age of 10 patients aged 12 to <18 years in trial 1 (a randomized, double-blind, placebo-controlled parallel-group study in adult and pediatric patients 12 years of age and older with hae). results of the subgroup analysis by age were consistent with overall study results. an additional 13 pediatric patients aged 12 to <18 years were enrolled in the open-label extension study [see adverse reactions (6.1), clinical pharmacology (12.3) and clinical studies (14)]. use of takhzyro for this indication in patients 2 to less than 12 years of age was supported by extrapolation of efficacy data from trial 1, an adequate and well controlled study in adult and pediatric (12 to less than 18 years of age) patients, with additional pharmacokinetic analyses showing similar drug exposures between adults (>18 years of age) and pediatric patients (2 to less than 12 years of age), and safety and pharmacodynamic data from an open-label, multicenter study in pediatric patients with hae aged 2 to less than 12 years that enrolled 21 patients (4 patients were aged 2 to less than 6 years and 17 patients were 6 to less than 12 years of age) [see adverse reactions (6.1) and clinical pharmacology (12.3)] . the pharmacodynamic response observed in this trial for pediatric patients 2 to less than 12 years of age was similar to that seen in adult and pediatric patients 12 years of age and older [see clinical pharmacology (12.2)] . the safety and effectiveness of takhzyro in pediatric patients less than 2 years of age have not been established. the safety and effectiveness of takhzyro were evaluated in a subgroup of patients (n=5) aged ≥65 years in trial 1. results of the subgroup analysis by age were consistent with overall study results [see adverse reactions (6.1), clinical pharmacology (12.3) and clinical studies (14)] . takhzyro® (tak-zye-roe) (lanadelumab-flyo) injection, for subcutaneous use single-dose 1 ml prefilled syringe this instructions for use contains information on how to inject takhzyro. please make sure to read, understand, and follow the instructions for use before injecting takhzyro. a healthcare provider should show you how to prepare and inject takhzyro properly before you use it for the first time. contact your healthcare provider if you have any questions. - takhzyro is a ready to use prefilled syringe (figure a ) for injection under the skin (subcutaneous) to be given to children by their healthcare provider or caregiver. self-injection is not recommended in children (2 to less than 12 years of age). - each takhzyro prefilled syringe contains one 150 mg/1 ml dose. the takhzyro prefilled syringe is for single use only. - store the takhzyro prefilled syringe in the refrigerator at 36°f to 46°f (2°c to 8°c). do not freeze. - store the takhzyro prefilled syringe in the original carton to protect it from light. - throw away (discard) the takhzyro prefilled syringe if it has been kept out of the refrigerator, frozen, or not kept in the original carton protected from light. - do not shake the takhzyro prefilled syringe. keep the takhzyro prefilled syringe and all medicines out of the reach of children. - do not use if the seal on the carton is open or broken. - your medicine is sensitive to warm temperatures. do not use heat sources such as a microwave or hot water to warm your takhzyro prefilled syringe. - do not remove the needle cap until you are ready to inject. - do not touch or push the plunger rod until you are ready to inject. - do not touch any surface or body part after washing your hands before the injection. - do not use the takhzyro prefilled syringe if the expiration date has passed. if the takhzyro prefilled syringe is expired throw it away (discard) in a sharps container and contact your healthcare provider. - do not use the takhzyro prefilled syringe if the syringe is damaged or cracked. - do not use the takhzyro prefilled syringe if the medicine is discolored, cloudy, or has flakes or particles in it. - you may see air bubbles in the takhzyro prefilled syringe. this is normal and will not affect your dose. - stomach area (abdomen) - thighs - upper arms - do not inject into an area where the skin is irritated, red, bruised, or infected. - the area you choose for injection should be at least 2 inches away from any scars or belly button (navel). - do not fan or blow on the clean site. - do not touch the clean site again before giving your injection. - do not touch or push the plunger rod until you are ready to inject. - do not use the takhzyro prefilled syringe if it has been dropped without the needle cap on. - do not use the takhzyro prefilled syringe if the needle looks damaged or bent. - do not touch the needle or allow the needle to touch anything. - do not recap the needle to avoid a needle-stick injury. - keep pinching until the injection is complete and the needle is removed (figure k ). - do not rub the injection site. there may be a small amount of blood where you injected. this is normal. - cover the injection site with an adhesive bandage if needed. - do not recap the needle to avoid a needle-stick injury. - do not reuse the takhzyro prefilled syringe or any of your injection supplies. - do not throw away (dispose of) the takhzyro prefilled syringe in your household trash. - do not touch the needle. fda-cleared sharps containers are generally available through pharmacies, medical supply companies, healthcare providers, and online. - if you do not have an fda-cleared sharps container, you may use a household container that is: made of a heavy-duty plastic can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out, upright and stable during use leak-resistant, and properly labeled to warn of hazardous waste inside the container. - made of a heavy-duty plastic - can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out, - upright and stable during use - leak-resistant, and - properly labeled to warn of hazardous waste inside the container. - when your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. there may be state or local laws about how you should throw away used needles and syringes. for more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to fda's website at: http://www.fda.gov/safesharpsdisposal. - important: always keep the sharps disposal container out of the reach of children. - do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. do not recycle your used sharps disposal container. questions? for product or service-related questions, call 1-877-takeda-7 (1-877-825-3327) or go to www.takhzyro.com. manufactured by: takeda pharmaceuticals u.s.a., inc. lexington, ma 02421 u.s. license no. 1898 takhzyro® is a registered trademark of dyax corp., a takeda company. takeda® and the takeda logo® are registered trademarks of takeda pharmaceutical company limited. ©2023 takeda pharmaceuticals u.s.a., inc. all rights reserved. this instructions for use has been approved by the u.s. food and drug administration. approved: 02/2023 takhzyro® (tak-zye-roe) (lanadelumab-flyo) injection, for subcutaneous use single-dose prefilled syringe this instructions for use contains information on how to inject takhzyro. please make sure to read, understand, and follow the instructions for use before injecting takhzyro. a healthcare provider should show you how to prepare and inject takhzyro properly before you use it for the first time. contact your healthcare provider if you have any questions. - takhzyro is a ready to use prefilled syringe (figure a ) for injection under the skin (subcutaneous) to be given by your healthcare provider, caregiver, or by yourself. - each takhzyro prefilled syringe contains one 300 mg/2 ml dose. the takhzyro prefilled syringe is for single use only. - store the takhzyro prefilled syringe in the refrigerator at 36°f to 46°f (2°c to 8°c). do not freeze. - store the takhzyro prefilled syringe in the original carton to protect it from light. - throw away (discard) the takhzyro prefilled syringe if it has been kept out of the refrigerator, frozen, or not kept in the original carton protected from light. - do not shake the takhzyro prefilled syringe. keep the takhzyro prefilled syringe and all medicines out of the reach of children. - do not use if the seal on the carton is open or broken. - your medicine is sensitive to warm temperatures. do not use heat sources such as a microwave or hot water to warm your takhzyro prefilled syringe. - do not remove the needle cap until you are ready to inject. - do not touch or push the plunger rod until you are ready to inject. - do not touch any surface or body part after washing your hands before the injection. - do not use the takhzyro prefilled syringe if the expiration date has passed. if the takhzyro prefilled syringe is expired throw it away (discard) in a sharps container and contact your healthcare provider. - do not use the takhzyro prefilled syringe if the syringe is damaged or cracked. - do not use the takhzyro prefilled syringe if the medicine is discolored, cloudy, or has flakes or particles in it. - you may see air bubbles in the takhzyro prefilled syringe. this is normal and will not affect your dose. - stomach area (abdomen) - thighs - upper arms (only if a healthcare provider or caregiver is giving you the injection) - do not inject into an area of your body where the skin is irritated, red, bruised, or infected. - the area you choose for injection should be at least 2 inches away from any scars or your belly button (navel). - do not fan or blow on the clean site. - do not touch the clean site again before giving your injection. - do not touch or push the plunger rod until you are ready to inject. - do not use the takhzyro prefilled syringe if it has been dropped without the needle cap on. - do not use the takhzyro prefilled syringe if the needle looks damaged or bent. - do not touch the needle or allow the needle to touch anything. - do not recap the needle to avoid a needle-stick injury. - keep pinching until the injection is complete and the needle is removed (figure k ). - do not rub the injection site. there may be a small amount of blood where you injected. this is normal. - cover the injection site with an adhesive bandage if needed. - do not recap the needle to avoid a needle-stick injury. - do not reuse the takhzyro prefilled syringe or any of your injection supplies. - do not throw away (dispose of) the takhzyro prefilled syringe in your household trash. - do not touch the needle. fda-cleared sharps containers are generally available through pharmacies, medical supply companies, healthcare providers, and online. - if you do not have an fda-cleared sharps container, you may use a household container that is: made of a heavy-duty plastic can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out, upright and stable during use leak-resistant, and properly labeled to warn of hazardous waste inside the container. - made of a heavy-duty plastic - can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out, - upright and stable during use - leak-resistant, and - properly labeled to warn of hazardous waste inside the container. - when your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. there may be state or local laws about how you should throw away used needles and syringes. for more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to fda's website at: http://www.fda.gov/safesharpsdisposal. - important: always keep the sharps disposal container out of the reach of children. - do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. do not recycle your used sharps disposal container. questions? for product or service-related questions, call 1-877-takeda-7 (1-877-825-3327) or go to www.takhzyro.com. manufactured by: takeda pharmaceuticals u.s.a., inc. lexington, ma 02421 u.s. license no. 1898 takhzyro® is a registered trademark of dyax corp., a takeda company. takeda® and the takeda logo® are registered trademarks of takeda pharmaceutical company limited. ©2022 takeda pharmaceuticals u.s.a., inc. all rights reserved. this instructions for use has been approved by the u.s food and drug administration. approved: 02/2022 be sure that you read, understand, and follow the instructions for use before injecting takhzyro. a healthcare provider should show you how to prepare and inject takhzyro properly before you use it for the first time . contact your healthcare provider if you have any questions. important information: - takhzyro is a ready-to-use solution for injection under the skin (subcutaneous). it is supplied in a single-dose, glass vial. - your healthcare provider will prescribe the dose that you should take. - only use the syringes, transfer needles, and injection needles that your healthcare provider prescribes. - only use the syringes, transfer needles and injection needles 1 time. throw away (dispose of) any used syringes and needles. storing takhzyro: - store takhzyro in the refrigerator at 36°f to 46°f (2°c to 8°c). do not freeze. - store takhzyro in the original carton to protect the vial from light. - do not shake takhzyro. - keep takhzyro and all medicines out of the reach of children. supplies needed for your takhzyro injection step 1: prepare for your injection - gather all supplies and place them on a well-lighted flat work surface. - take the vial out of the refrigerator 15 minutes before use and allow it to reach room temperature before preparing an injection. - check the expiration date on the box and vial label of takhzyro. do not use if the expiration date has passed. - check the supplies for damage. do not use if they appear damaged. - clean your work area and wash your hands before preparing your dose. do not touch any surface or body part, especially your face, after washing your hands before injection. - remove the vial from the packaging. do not use the vial if the plastic cap covering is missing. - gently turn the vial upside down (invert) 3 to 5 times to mix the medicine. do not shake to avoid foaming. - look at the medicine in the vial for visible particles or a change in the color. medicine should be colorless to slightly yellow. do not use if you see particles or a change in color. - remove the plastic cap from the medicine vial. do not remove the medicine vial rubber stopper. - place the vial on a flat surface. clean the medicine vial rubber stopper with an alcohol wipe and allow it to dry. step 2: attach transfer needle to syringe - screw the 18g transfer needle to the 3ml syringe. - pull back the plunger to fill the syringe with air equal to the amount of medicine in the vial. - hold the syringe by the barrel with one hand and the transfer needle cap with the other hand. - pull off the transfer needle cap straight away from the syringe and away from your body. do not pull on the plunger. place the transfer needle cap down on a clean flat surface. - do not touch the needle tip. step 3: transfer takhzyro into syringe and switch to the injection needle - keep the vial on the flat surface and insert the transfer needle into the center of the rubber stopper. - push the plunger down to inject air into the vial and hold the plunger down. - slowly turn the vial upside down with transfer needle and syringe attached. pull back on the plunger to withdraw the full dose in the vial. - remove large air bubbles by gently tapping on the syringe barrel with your fingers until the bubbles rise to the top of the syringe. - slowly push the plunger, allowing air to go back into the vial, until the medicine reaches the top of the syringe. - repeat these steps until large air bubbles are removed. - return the vial to an upright position. - without removing the needle from the vial, unscrew the syringe by holding the needle hub and turning the syringe counter clockwise. - return the syringe to an upright position. - throw away the 18g transfer needle and the vial in a sharps disposal container (see step 6). - screw the 27g ½-inch injection needle to the syringe. step 4: select and prepare injection site - takhzyro can be self-injected in your stomach (abdomen) or thigh. if given by a caregiver, takhzyro may also be injected in the upper arm. - clean your injection site with an alcohol wipe and allow it to dry completely. - you should use a different injection site each time you receive an injection to keep your skin healthy. - the area you choose for injection should be at least 2 inches (5 cm) away from any scars or your belly button (navel). do not choose an area that is bruised, swollen, or painful. - takhzyro should be given within 2 hours of preparing the dosing syringe at room temperature. after the dosing syringe is prepared, it can be refrigerated at 36°f to 46°f (2°c to 8°c) and must be used within 8 hours of preparation. take the dosing syringe out of the refrigerator 15 minutes before use and allow it to reach room temperature prior to injecting. step 5: inject takhzyro - hold the syringe by the barrel with one hand and the injection needle cap with the other hand. - pull off the injection needle cap straight away from the syringe and away from your body. do not pull on the plunger. do not touch the needle tip or allow it to touch any other surface. - gently pinch about 1 inch of skin at your cleaned chosen injection site and insert the needle. - push the plunger slowly until no medicine remains in the syringe. release the skin fold and gently remove the needle. do not recap the needle. step 6: throw away (dispose of) needle and syringe - place the 27g ½-inch injection needle and the syringe in a sharps container. - if you do not have a fda-cleared sharps disposal, you may use a household container that is: made of heavy-duty plastic, can be closed with a tight fitting, puncture-resistant lid, without sharps being able to come out, upright and stable during use, leak-resistant, and - made of heavy-duty plastic, - can be closed with a tight fitting, puncture-resistant lid, without sharps being able to come out, - upright and stable during use, - leak-resistant, and - properly labeled to warn of hazardous waste inside the container. - when your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. there may be state or local laws about how you should throw away used needles and syringes. for more information about safe sharps disposal, and for specific information about sharps in the state you live in, go to the fda's website at: http://www.fda.gov/safesharpsdisposal. important: always keep the sharps disposal container out of the reach of children. for more information, visit www.takhzyro.com this instructions for use has been approved by the u.s. food and drug administration. manufactured by: takeda pharmaceuticals u.s.a., inc. lexington, ma 02421 u.s. license no: 1898 takhzyro® is a registered trademark of dyax corp., a takeda company. takeda® and the takeda logo® are registered trademarks of takeda pharmaceutical company limited. ©2021 takeda pharmaceuticals u.s.a., inc. all rights reserved. approved: 11/2021

אוסטרליה - אנגלית - Department of Health (Therapeutic Goods Administration)

takeda pharmaceuticals australia pty ltd - lanadelumab, quantity: 300 mg - injection, solution - excipient ingredients: citric acid monohydrate; water for injections; dibasic sodium phosphate dihydrate; polysorbate 80; histidine; sodium chloride - takhzyro is indicated for routine prevention of recurrent attacks of hereditary angioedema (c1-esterase-inhibitor deficiency or dysfunction) in patients aged 12 years and older.