Aprotinin

B02B - Vitamin K and other haemostatics ATC B02BC,V03AK Unknown approved 1993 Parenteral Withdrawn Black-box warning

JFDA label: Tisseel Lyo

⚠ Black-Box Warning

Drug Withdrawn from Market — ChEMBL drug_warning (Withdrawn) | United States | Increased mortality

Mechanism of Action

Inhibitor of Plasminogen — Plasminogen inhibitor; Inhibitor of Plasma kallikrein — Plasma kallikrein inhibitor

Target	Action	Gene / class
Plasma kallikrein efficacy	INHIBITOR	KLKB1
Plasminogen efficacy	INHIBITOR	PLG

Indications

Approved

Hemorrhage — hemorrhage

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (22)

Not Known Acute coronary syndrome · Arrhythmia · Arrhythmia supraventricular · Atrial fibrillation · Atrial flutter · Atrioventricular block · Bradycardia · Cardiac arrest · Cardiac disorder · Cardiac failure · Cardiac failure congestive · Coronary artery occlusion · Infarction · Myocardial infarction · Myocardial ischaemia · Pericarditis · Supraventricular tachycardia · Tachycardia · Ventricular arrhythmia · Ventricular extrasystoles · Ventricular fibrillation · Ventricular tachycardia

Vascular disorders (9)

Not Known Arterial thrombosis · Embolism · Haemorrhage · Hypertension · Hypotension · Peritoneal haemorrhage · Phlebitis · Thrombophlebitis · Thrombosis

Nervous system disorders (4)

Not Known Cerebral artery embolism · Cerebrovascular accident · Convulsion · Dizziness

Hepatobiliary disorders (4)

Not Known Alanine aminotransferase increased · Hepatic failure · Jaundice · Liver function test abnormal

Renal and urinary disorders (6)

Not Known Renal failure · Renal failure acute · Renal impairment · Renal tubular necrosis · Urinary retention · Urinary tract disorder

Blood and lymphatic system disorders (4)

Not Known Anaemia · Disseminated intravascular coagulation · Haemoglobin · Thrombocytopenia

Immune system disorders (3)

Not Known Anaphylactic shock · Hypersensitivity · Immune system disorder

Metabolism and nutrition disorders (2)

Not Known Hyperglycaemia · Hypokalaemia

Gastrointestinal disorders (6)

Not Known Constipation · Diarrhoea · Dyspepsia · Gastrointestinal haemorrhage · Nausea · Vomiting

Skin and subcutaneous tissue disorders (4)

Not Known Dermatitis · Pruritus · Rash · Urticaria

Musculoskeletal and connective tissue disorders (2)

Not Known Arthralgia · Musculoskeletal discomfort

Psychiatric disorders (4)

Not Known Agitation · Anxiety · Confusional state · Insomnia

Infections and infestations (4)

Not Known Infection · Pneumonia · Sepsis · Urinary tract infection

Investigations (3)

Not Known Blood creatine phosphokinase increased · Body temperature increased · Feeling abnormal

General disorders and administration site conditions (19)

Not Known Acidosis · Anaphylactoid reaction · Angiopathy · Asthenia · Atelectasis · Bundle branch block · Chest pain · Coagulopathy · Fluid overload · Ischaemia · Leukocytosis · Multi-organ failure · Oedema peripheral · Oliguria · Pericardial effusion · Pneumothorax · Shock · Skin discolouration · Urethral disorder

Respiratory, thoracic and mediastinal disorders (12)

Not Known Apnoea · Asthma · Bronchospasm · Cough · Dyspnoea · Hypoxia · Lung disorder · Pleural effusion · Pulmonary embolism · Pulmonary hypertension · Pulmonary oedema · Pulmonary thrombosis

Chemistry & Properties

CAS	9087-70-1
PubChem CID	16130295

SMILES

CCC(C)C1C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NCC(=O)NC(C(=O)NC2CSSCC3C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(CSSCC(C(=O)NC(C(=O)NC(C(=O)N4CCCC4C(=O)N5CCCC5C(=O)NC(C(=O)NC(C(=O)NCC(=O)N6CCCC6C(=O)NC(CSSCC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)N3)CC(=O)O)CCC(=O)O)C)CO)CCCCN)CC7=CC=CC=C7)CC(=O)N)CC(=O)N)CCCNC(=N)N)CCCCN)C)CCCNC(=N)N)NC(=O)CNC(=O)CNC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC2=O)CCC(=O)N)C(C)O)CC8=CC=CC=C8)C(C)C)CC9=CC=C(C=C9)O)C(=O)NC(C(=O)NC(C(=O)NC(C(=O)N1)CCCNC(=N)N)C)CCCCN)C(C)O)CC1=CC=C(C=C1)O)CCC(=O)O)CC(C)C)NC(=O)C(CC1=CC=CC=C1)NC(=O)C(CC(=O)O)NC(=O)C1CCCN1C(=O)C(CCCNC(=N)N)N)C(=O)NCC(=O)NCC(=O)NC(C)C(=O)O)C(C)O)CCCNC(=N)N)CCSC)CC(C)C)C)CCCCN)C)CC(=O)N)CC1=CC=C(C=C1)O)CC1=CC=CC=C1)CC1=CC=C(C=C1)O)CCCNC(=N)N)C(C)CC

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	22.428 h
Volume of distribution	0.072 L/kg
Protein binding	-111.8%
BBB penetrant	No

Receptor binding (top 1)

Target	Action	Affinity
plasminogen (PLG)	Inhibitor	pIC50 6.8

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Drug–drug interactions (6, DDInter)

Interacting drug	Severity	Management
Anti-inhibitor coagulant complex	major
Factor IX Complex (Human)	major
Tretinoin	major
Alteplase	moderate
Reteplase	moderate
Tenecteplase	moderate

Registered Products (2)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Tisseel Lyo	Solution 15000 kIU/10 ml, 455 mg/10 ml, 200 MMO/10 ml, 2500 IU/10 ml	10 ml	Khoury Drug Store	—
Tisseel Lyo	Solution 6000 kIU/4 ml, 182 mg/4 ml, 80 MMO/4 ml, 1000 IU/4 ml	4 ml	Khoury Drug Store	—