WarningH302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]P203, P260, P263, P264, P270, P280, P301+P317, P318, P330, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 39 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
Regulatorische Informationen
Dothiepin: Does not have an individual approval but may be used under an appropriate group standard
Hazard Classes and Categories
Acute Tox. 4 (100%)
Entsorgungsverfahren
SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air qualitypotential migration in soil or watereffects on animal, aquatic, and plant lifeand conformance with environmental and public health regulations.
Körperbelastung
The plasma dothiepin level was 4.5 ug/mL, with the northiaden metabolite at 1.28 ug/mL /in a 36- year old woman /who/ ingested 2 to 3 g of dothiepin.Blood concentrations of dothiepin were measured in comparison in five of the volunteers. The mean blood/plasma ratio was 0.7 (0.6-0.8) /after seven healthy volunteers received a single oral dose of 75 mg dothiepin./
Wechselwirkungen
Seizures or arrhythmias may be precipitated /SRP: by flumazenil/ in patients with a serious cyclic antidepressant overdose. /Flumazenil/
Milk Concentrations
Dothiepin and its metabolites have been detected in breast milk. The mean total daily infant exposure amounts to about 4.4% of the maternal dothiepin dosage.
Human Toxicity Excerpts
/CASE REPORTS/ To assess the clinical toxicity of dothiepin and other tricyclic antidepressants in overdose, 287 patients admitted for tricyclic poisoning were evaluated for seizures, tachyarrhythmias, sedation, and electrocardiographic changes. Results indicated that 75 of the patients had taken dothiepin. General seizures were more likely after dothiepin than after other tricyclic antidepressants (9/67 vs 5/220) as were arrhythmias (4/67 vs 3/220). In addition, the dothiepin group had ingested a larger dose, attributable to the larger average tablet strength.
Anwendungen & Verwendung
History
Described in the 1960s by the Czech company Sdruzeni Podniku pro Zdravotnickon Vyrobu; SPOFA (Spofa, 1962)
Verwenden
A tricyclic antidepressant.
/CASE REPORTS/ Ingestion of 1 to 4.5 g of dothiepin by a series of eight adults was followed by impaired consciousness (7/8), grand mal seizures (2/8), and tachycardia (7/8). All survived. An adult man ingested 1.5 g of dothiepin and became comatose, developing cardiac arrest within minutes of arrival at a hospital
he survived.
/CASE REPORTS/ A 41 year old man was admitted following an overdose of 40, 25 mg pills of dothiepin. He was drowsy but otherwise well. ECG on admission showed only minimal broadening of the QRS consistent with a tricyclic overdose, but symmetrical T wave repolarisation abnormalities appeared within nine hours mimicking an acute anteroseptal myocardial infarction. Serial cardiac enzyme estimates (creatine kinase and aspartate transaminase) did not confirm an ischemic event. Cross sectional echocardiography was normal with no evidence of focal hypokinesis. ECG changes persisted for six weeks. An exercise tolerance test following the Bruce protocol was normal. Coronary angiography was performed three months later after the patient complained of exertional chest pain. This was also normal. Such changes in ventricular repolarisation are rare but are a reminder of the electrical dangers inherent in tricyclic use. The changes in conduction were likely to be due either to the quinidine-like activity of dothiepin, or to an alteration in membrane permeability allowing differences in potassium concentrations between different areas of the myocardium, rather than to any ischemic damage to the myocardium.
/CASE REPORTS/ A 36 year old woman ingested 2 to 3 g of dothiepin, developed ventricular tachycardia, and was treated with gastric lavage and charcoal hemoperfusion, but she began to hallucinate 48 hours after ingestion. At 56 hours postoverdose, she became apneic with ventricular fibrillation. The plasma dothiepin level was 4.5 ug/mL, with the northiaden metabolite at 1.28 ug/mL. Patients with only mild sedation and normal limb-lead QRS width may still have complications.
/CASE REPORTS/ A case of inappropriate ADH syndrome associated with dothiepin therapy, initially given at a dose of 75 mg then increased to 150 mg/day, is reported in a 39-yr-old depressed man with pancytopenia and portal hypertension. The patient became drowsy, disoriented and confused, and had persistent hyponatremia and raised arginine-vasopressin levels. Dothiepin was stopped and the patient was treated with fluid restriction and subsequently, demeclocycline. Serum sodium and osmolality returned to normal in 4 days and arginine vasopressin concentrations returned to normal.
Antidote and Emergency Treatment
The high degree of protein binding, together with the extensive volume of distribution, tends to preclude the potential usefulness of hemodialysis and hemoperfusion.Following a dothiepin overdose leading to ventricular fibrillation and cardiac arrest, an adult was treated with intravenous sodium bicarbonate, dopamine, and lidocaine with hyperventilation. His condition remained unstable. One hour later, intravenous sodium chloride ... was given over 5 minutes. The blood pressure rose immediatelythe QRS complexes narrowed and cardiac abnormalities became less frequent. Similar episodes of hypotension and cardiac abnormalities over the following days were reversed by rapid infusion of sodium chloride.Treatment consists largely of gastric lavage and activated charcoal (either single or multiple doses). Although use of activated charcoal suggests a role in decreasing the half-life of dothiepin, other studies with TCAs show little or no such significant decrease in half-life.Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/For more Antidote and Emergency Treatment (Complete) data for DOTHIEPIN (8 total), please visit the HSDB record page.
Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Human Toxicity Values
Death has followed ingestion of 50 25 mg capsules of dothiepin (total dose, 1250 mg).
