Hi, as the SN method is quite popular and my preferred way to go, I really appreciate your input. I've read some research on potential side effects from AE's, so could you do a search on Metoclopramide and Domperidone?
I'm not quite sure if they're included in the database itself due to being prescription medicine, but I'd assume that in high enough doses, they'd be toxic.
Oh, and if possible please also check Midazolam.
Metoclopramide
Type of Product
Anti-emetic drug with antagonistic effects at dopamine receptors.
Ingredients
Metoclopramide hydrochloride
Tablets - 10 mg
Oral solution (150 mL container) - 5 mg/5 mL
Injection (2 mL ampoules) - 5 mg/mL (Available in Ireland)
NOTE Combination products with paracetamol or aspirin are available. Please consult the relevant TOXBASE entry.
Toxicity
The most common toxicity includes extrapyramidal effects such as acute dystonias which may occur even at therapeutic doses, particularly in children, young adults and the very old. Poor CYP2D6 metabolisers (Chua et al, 2019; Akbuga-Ozel, 2017) and pregnant women (Chua et al, 2019) may also be at risk of developing acute dystonias.
A 62-year-old female developed severe bradycardia then asystolic cardio-respiratory arrest within one minute of a 10 mg IV injection of metoclopramide (Rumore et al, 2011). Spontaneous circulation recovered following chest compressions and she was transferred to intensive care where she developed SVT. She ultimately made a full recovery. Several other cases of bradycardia and cardio-respiratory arrest following IV metoclopramide have been reported in the literature (Rodrigues et al, 2019).
A metoclopramide-induced acute hypertensive crisis complicated by multi organ injury, myocardial infarction and acute respiratory distress syndrome requiring vvECMO was observed in a 36-year-old woman with pheochromocytoma (Leonard et al, 2018).
Severe extrapyramidal symptoms have been reported in a 4.5-month-old infant who received 15 mg (2 mg/kg) metoclopramide over 12 hours (Sahin et al, 2001) and in a 6-month-old child who received 3 mg/kg metoclopramide over 9 hours (Batts & Munter, 1998). In both cases, symptoms resolved with supportive care.
A 3-week-old male infant became cyanotic, lethargic and irritable after receiving an iatrogenic overdose of metoclopramide (6 mg/kg over 36 hours) for the treatment of suspected gastroesophageal reflux. Methaemoglobinaemia (20.5%) resolved following a single intravenous dose of methylthioninium chloride (Kearns & Fiser, 1988).
Neuroleptic malignant syndrome has been reported in a 58-year-old man with
C. difficile diarrhoea after ingestion of 50 mg metoclopramide over 3 days. He recovered with supportive care (Supariwala et al, 2011).
Serotonin toxicity has rarely been described following exposure to metoclopramide. A 19-month-old child developed seemingly overlapping symptoms of both neuroleptic malignant syndrome and serotonin toxicity following oral therapeutic dosing (Aussedat et al, 2020). A 40-year-old woman developed serotonin toxicity after an IM injection of metoclopramide (Harada et al, 2017).
After oral administration of a therapeutic dose, peak plasma concentrations of metoclopramide occur after 1 to 2 hours. The elimination half-life is 4-6 hours (Martindale, 2010), which may be prolonged (up to 19 hours) in patients with impaired renal function and in infants. A half-life of 23 hours has been reported in a 3-week-old infant (Kearns et al, 1988).
Features
Acute dystonic reactions such as oculogyric crises, spasmodic torticollis, trismus and sensation of tongue swelling are the commonest features. They are most likely in children and young or pregnant women and may occur at therapeutic doses. Extrapyramidal features usually resolve after drug discontinuation although symptoms may persist for up to 36 hours.
Bradycardia, hypotension, ECG abnormalities (including QT prolongation), and cardio-respiratory arrest have been reported following IV administration. Metoclopramide may induce acute hypertensive crises in patients with pheochromocytoma.
Headache, dizziness, drowsiness, decreased conscious level, confusion, hallucinations and convulsions have been reported.
Methaemoglobinaemia has rarely been reported in neonates and infants. Neuroleptic malignant syndrome has been reported after therapeutic use and overdose.
Co-ingestion of alcohol and other central nervous system depressants may potentiate the sedative effect of metoclopramide.
Although rare, serotonin toxicity has been reported and may occur alongside acute dystonic reactions, particularly in patients on other serotonergic medications.
If taken with other serotonergic agents there is a greater risk of serotonin toxicity.
Domperidone
Type of Product
Selective peripheral dopamine antagonist at the D2 dopamine receptor. Used for control of nausea and vomiting. Domperidone has also been used to increase breast milk production in lactating women (unlicenced indication).
Ingredients
Domperidone
Tablets - 10 mg
Orodispersible tablets - 10 mg
Oral suspension (100 or 200 mL bottle) - 1 mg/mL
Toxicity
Domperidone may cause cardiac potassium channel blockade resulting in QT prolongation and torsade de pointes. It may cross the blood brain barrier, especially in infants and young children, and occasionally cause acute dystonia and neuroleptic malignant syndrome due to antagonist actions at central dopamine D2 receptors.
A 69-year-old man who was receiving chemotherapy with bleomycin, cisplatin and methotrexate for oesophageal cancer developed ventricular fibrillation and died after an IV bolus of 100 mg domperidone (Joss et al, 1982). Lower doses of IV domperidone (50 mg and 20 mg) have been associated with ventricular arrhythmias in the context of hypokalaemia (Roussak & Carey 1984). Of four chemotherapy patients given domperidone 20 mg IV bolus, followed by 10 mg/kg over 24 hours, one developed ventricular tachycardia; potassium concentration was 2.9 mmol/l at the time (Osborne et al, 1985).
A 3-month-old infant was accidentally given 50 mg domperidone and developed dystonic eye and limb movements, persistent tachycardia and hyperkalaemia with ECG showing SVT. Features resolved after 36 hours of supportive treatments (Sanklecha & Charde, 2013).
Domperidone is rapidly absorbed with peak plasma concentrations occurring approximately 60 minutes after ingestion (in fasting subjects). The therapeutic plasma half-life is 7-9 hours following oral administration (this may be prolonged in hepatic and renal insufficiency) (Motilium SPC, 2021).
Features
Clinical features include dry mouth, GI upset, fatigue, drowsiness, dizziness, anxiety, extrapyramidal symptoms. Convulsions, coma and neuroleptic malignant syndrome may occur.
Intravenous boluses given to patients with pre-existing heart conditions, hypocalcaemia or undergoing cytotoxic chemotherapy have resulted in cardiac arrhythmias, convulsions, cardiac and respiratory arrest and death.
Hi, as the SN method is quite popular and my preferred way to go, I really appreciate your input. I've read some research on potential side effects from AE's, so could you do a search on Metoclopramide and Domperidone?
I'm not quite sure if they're included in the database itself due to being prescription medicine, but I'd assume that in high enough doses, they'd be toxic.
Oh, and if possible please also check Midazolam.
Midazolam
Type of Product
A short-acting benzodiazepine used for sedation and treatment of seizures.
Ingredients
Midazolam
Buccal liquid - 5 mg/mL (0.5 mL vial, 1 mL vial, 1.5 mL vial, 2 mL vial)
Oral mucosal solution - 2 mg/mL (5 mL amp), 5 mg/mL (7.5 mL in 15 mL bottle)
Oral mucosal solution (in pre-filled oral syringe) - 5 mg/mL (2.5 mg, 5 mg, 7.5 mg, 10 mg syringes), 10 mg/mL (1 mL)
Buccal liquid - 10 mg/mL (1 mL vial)
Injection - 1 mg/mL (2 mL amp, 5 mL amp, 5 mL pre-filled syringe)
Injection - 2 mg/mL (5 mL amp)
Injection - 5 mg/mL (1 mL amp, 2 mL amp, 3 mL amp, 5 mL amp, 10 mL amp)
Solution for Infusion - 1 mg/mL, 2 mg/mL (25 mL and 50 mL vials)
Nasal spray - 2.5 mg, 3.75 mg, 5 mg (single-dose containers, available in Ireland)
Toxicity
The primary toxicity of benzodiazepines is CNS depression; the effects are potentially more severe when co-ingested with alcohol and other CNS depressants.
Fatal accidental iatrogenic midazolam overdose has been reported (Michalodimitrakis et al, 1999).
A term baby sedated on intensive care with midazolam for 32 hours and morphine for 62 hours remained unresponsive until day 5 following discontinuation and recovered fully by day 7 (Gupta et al, 2013).
Midazolam is absorbed rapidly following oromucosal administration and intramuscular injection. Extensive first-pass metabolism results in a low systemic bioavailability following ingestion (Martindale, 2011). The elimination half-life following therapeutic doses in healthy volunteers is 1.5-2.5 hours (Midazolam SPC, 2018).
Features
Benzodiazepines commonly cause drowsiness, ataxia, dysarthria and nystagmus. Coma, hypotension, bradycardia and respiratory depression occasionally occur but are seldom serious if these drugs are taken alone. Coma usually lasts only a few hours but may be prolonged in elderly patients.
Benzodiazepine respiratory depressant effects are more serious in patients with chronic obstructive airways disease. Severe effects in overdose also include rhabdomyolysis and hypothermia.
ECG abnormalities include transient first degree and second degree block and QT prolongation. Abnormal LFTs may also occur.
Microembolisation can result from intravenous injection of crushed tablets. Accidental intra-arterial injection of benzodiazepines can cause severe limb ischaemia and gangrene necessitating limb amputation.
Co-ingestion of alcohol and other central nervous system depressants potentiates the effects of benzodiazepines and can increase toxicity.
What do you have for Propranolol and 1,4 Butaniol ?
Thank you for making the knowledge available to us
Propranolol
Type of Product
Non-selective beta-adrenergic blocker with sodium-channel blocking properties.
Ingredients
Propranolol
Tablets - 10 mg, 40 mg, 80 mg, 160 mg
Oral solution - 5 mg/5 mL, 10 mg/5 mL, 40 mg/5 mL, 50 mg/5 mL
Sustained release capsules - 80 mg, 160 mg
Toxicity
Severe toxicity in overdose is from blockade of sodium-channels (similar to severe tricyclic antidepressant poisoning) and blockade of beta-adrenergic receptors (similar to beta-blocker poisoning). Propranolol is lipid soluble so will also penetrate the CNS to cause convulsions or coma.
Individual response varies greatly. Death has followed ingestion of about 2 g (Suarez et al, 1988) and survival after ingestion of 8 g (Tynan et al, 1981).
In one case series the smallest dose which caused symptoms in a child was 5 mg/kg (Belson et al, 2001).
A 7-month-old infant who had accidentally been administered propranolol 6 mg/kg three times daily instead of 0.6 mg/kg three times daily for the treatment of scalp haemangioma developed tachypnoea and lethargy. On arrival in the ED oxygen saturation varied from 96% to 100% on room air, ECG showed sinus bradycardia (62 beats/min versus normal of 100-150 beats/min). Treatment included intravenous fluid boluses of 0.9% sodium chloride and high dose insulin, dextrose, and intravenous lipid emulsion. Following completion of these treatments, haemodynamic stability was regained. The infant was observed in PICU and discharged home the following day (Thompson et al 2016).
A 24-year-old female who ingested 7360 mg of propranolol developed wide QRS, coma, hypotension, VF, VT and multiple PEA arrests despite 100 mL 8.4% sodium bicarbonate, isoprenaline, adrenaline and glucagon. After a second dose of 300 mL of 8.4% sodium bicarbonate she stabilised and returned to a narrow complex sinus rhythm (Shanker et al, 2003).
Risk of convulsions is higher with propranolol than the other beta-blockers (Mokhlesi et al, 2003).
Peak plasma concentrations occur after 1-2 hours. The half-life in therapeutic use is about 3-6 hours but may increase to 10-20 hours with the modified release preparation (Propranolol 160mg SR capsules SPC, 2020).
Features
Key features in severe poisoning are cardiovascular collapse, CNS depression and convulsions.
Cardiac - QRS widening on ECG, hypotension, bradycardias and other arrhythmias including 1st – 3rd degree AV block. May produce VF, VT, or asystole in severe poisoning.
Development of cardiovascular complications is more likely if other cardioactive drugs, especially calcium channel blockers, digoxin, cyclic antidepressants or neuroleptics have also been ingested. The elderly and those with underlying ischaemic heart disease are at risk of developing severe cardiovascular compromise. Clinical features common to cardiac/cardiotoxic agents involved in mixed overdoses may be more severe or prolonged.
CNS - drowsiness, confusion, convulsions, hallucinations, dilated pupils and in severe cases coma. Neurological signs such as coma or absence of pupil reactivity are unreliable prognostic indicators during resuscitation or assessment of brain death.
Other - bronchospasm, pulmonary oedema and hyperkalaemia are possible.
What do you have for Propranolol and 1,4 Butaniol ?
Thank you for making the knowledge available to us
Butaniol Highly Toxic Substance
Type of Product
GHB and its analogues (GBL, 1,4-BD, GVL and GHV) are sedative drugs of abuse, which are also used as body-building agents.
Sodium oxybate is a liquid preparation of the GHB sodium salt, used in the treatment of narcolepsy. It is available as a 500 mg/mL oral solution, under the brand name
Xyrem.
GBL and 1,4-BD are metabolised to GHB. They are organic industrial solvents found in products such as acetone-free nail polish removers, paint strippers, cleaning products, and glue debonders.
Gamma-hydroxyvaleric (GHV) is a 4-methyl-substituted analogue of GHB, reported to be a direct GABA receptor agonist. Gamma-valerolactone (GVL) is a precursor of GHV.
Ingredients
GHB sodium salt is a white solid. It dissolves in water to form a clear, colourless and often tasteless liquid. It is presented as either a liquid or a powder (loose, or as tablets/capsules).
GBL and 1,4-BD are colourless liquids. They can be obtained from commercially available solvents.
Caution: the purity of the ingredients in recreational drugs may vary greatly.
Toxicity
GHB occurs endogenously in the brain at low concentrations. It is an agonist at GABA-B and GHB receptors (Busardò & Jones, 2015).
GBL and 1,4-BD are precursors for GHB. The latter may cause delayed toxicity when co-ingested with alcohol due to enzyme inhibition and delayed conversion of 1,4-BD to GHB (Schneidereit, 2000). High anion gap metabolic acidosis with raised anion gap has been reported following overdose of 1,4-butanediol (Stefani & Roberts, 2020).
GHB is rapidly absorbed from the gut with peak effects occurring 30-60 minutes post-ingestion. GHB is metabolised to carbon dioxide and water. The elimination half-life is between 20-60 minutes and prolonged in patients with hepatic impairment (Schep et al, 2012).
Severe clinical features may occur due to:
• Acute toxicity
• Severe withdrawal reactions after dose-reduction or abstinence following prolonged use
Click
here for information on cases.
Features of acute toxicity include CNS and respiratory depression, hypersalivation, bradycardia and hypotension. Clinical effects are potentiated by ethanol, benzodiazepines, antipsychotics and other CNS depressants, including some co-ingested recreational drugs.
Click here for further details on clinical features and management of toxicity due to GHB and analogues.
Features of withdrawal include severe agitation, hallucinations, insomnia, tachycardia and hypertension.
Click here for further details on clinical features and management of withdrawal from GHB and analogues.
Can I have info on diphenhydramine, also ethylene glycol, also sertraline please.
Diphenhydramine
Type of Product
A 1st generation sedating anti-H1 antihistamine with sodium and potassium channel blocking activity. Used in the treatment of allergic conditions, as a sleep aid, and in cold and flu combinations.
Diphenhydramine is also abused for sedative and hallucinogenic effects.
Ingredients
Diphenhydramine
Tablets - 25 mg, 50 mg
Oral Solution - 2 mg/mL
Cream - 2% w/w
May be found as an active ingredient in combination products - please see specific TOXBASE entry for details.
Toxicity
Toxicity manifests principally as sedation and central and peripheral anticholinergic features. Severe cardiotoxicity is also possible due to sodium channel blockade.
Following overdose in adults, moderate features (agitation, hallucinations, ECG abnormalities) have been associated with ingestions of greater than 300 mg and severe features (delirium, convulsions, coma) associated with doses greater than 1 g diphenhydramine (Radovanovic et al, 2000).
A retrospective study of 863 patients in the US found that acidosis, a raised anion gap and a prolonged QRS were the symptoms most associated with a severe outcome after ingestion of diphenhydramine. Severe outcomes were defined as the development of convulsions, ventricular dysrhythmias or intubation, 15.6% (n=135) of patients developed one or more severe outcome with convulsions being the most common (occurred in 98 cases (11.6%)). Three deaths were reported and all had one or more severe outcome prior to death (Hughes et al, 2021).
A 29-year-old male ingested 25 g of diphenhydramine and developed coma, convulsions and Brugada pattern ECG. He was treated with sodium bicarbonate and ventilation and subsequently recovered fully (Levine & Lovecchio, 2010).
A retrospective study of 42 adult and paediatric ingestions of diphenhydramine found that there was an increased risk of QRS prolongation and cardiotoxicity among patients who had ingested more than 1.5 g (Hughes & Hendrickson, 2018).
A 33-year-old male developed coma, tonic-clonic seizures, cardiac arrest and died after ingestion of 4.9 g of diphenhydramine (Yu et al, 2016).
A 23-year-old male who ingested up to 2.5 g developed cardiotoxicity with prolonged QRS (172 msec) and QTc (577 msec) and hypotension, recurrent convulsions and lactic acidosis. He underwent DC cardioversion and was treated with sodium bicarbonate and intralipid before the broad complex tachycardia resolved and he made a complete recovery (Abdi et al, 2014).
Young children can be more sensitive to the effects of overdose. Doses greater than 10 mg/kg have been reported to produce severe toxicity (Scharman et al, 2006) with five fatalities reported to be associated with diphenhydramine administration (Baker et al, 2003).
A 13-month-old child was admitted following a convulsion after being found with an empty bottle of diphenhydramine and 24 x 25 mg missing tablets. She had dilated pupils, nystagmus and altered mental status. ECG showed sinus tachycardia with a prolonged QRS duration of 130 ms. The ECG normalised following sodium bicarbonate therapy (Cole et al, 2011).
Few data are available regarding absorption of topically applied diphenhydramine; however, toxicity in children has been reported (Huston et al 1990; Turner, 2009). In the most serious case, a 17-month-old child died following use of a topical diphenhydramine cream; autopsy results showed the child's blood contained 20 times the normal therapeutic dose.
After therapeutic doses, peak plasma concentrations occur at 1-4 hours and the elimination half-life ranges from 2.4-9.3 hours (Martindale, 2019). Diphenhydramine is an inhibitor of CYP2D6 and interactions can occur following usage of drugs metabolised by this system (Nytol Original SPC, 2019).
Features
Key features include sedation and anti-cholinergic effects.
Peripheral anticholinergic effects include flushing, dilated pupils, blurred vision, dry mouth and tongue, hot dry skin, fever, decreased gastric motility and urinary retention. There may also be transient bradycardia followed by sinus tachycardia, hypertension, nausea, vomiting and tachypnoea.
Central anticholinergic effects include ataxia, delirium, agitation, aggression, visual and auditory hallucinations, speech disorders, convulsions, myoclonus, hypertonia and hyperthermia. In severe cases CNS excitation may give way to CNS depression, circulatory and respiratory failure and coma.
Other cardiac features may include cardiac conduction abnormalities including QRS and QT prolongation, ventricular dysrhythmias including torsade de pointes, ventricular fibrillation and cardiac arrest can occur.
Other features may include paralytic ileus, hyperglycaemia, rash and glaucoma. Abnormal liver and renal function and rhabdomyolysis have also been reported. Patients who have been unconscious may be hypothermic.
Less commonly than anticholinergic toxicity, serotonin toxicity may occur; click
here for features and management .
Clinical features common to cardiac/cardiotoxic agents involved in mixed overdoses may be more severe or prolonged.
Features may also be prolonged due to continued drug absorption from a pharmacobezoar in the gastrointestinal tract.
Ethylene Glycol Highly Toxic Substance
Type of Product
Antifreeze, coolant, brake fluid etc. A clear, viscous fluid with a sweetish taste. When used as an antifreeze it may be coloured with dye.
Synonyms
1,2-dihydroxyethane, 2-hydroxyethanol, ethylene alcohol, ethylene dihydrate, EG, glycol, glycol alcohol, glycolmonomer, MEG, monoethylene glycol.
CAS 107-21-1
Ingredients
Ethylene Glycol (1,2-Ethanediol)
Toxicity
Highly toxic. Ethylene glycol is an alcohol and will cause features of intoxication. However, its main toxicity follows its metabolism to glycolaldehyde then to glycolic, glyoxylic and oxalic acids. Glycolic acid is cleared by the kidney and is largely responsible for the marked acidosis seen in severe cases. There is increasing evidence that calcium oxalate monohydrate crystals are the cause of renal failure and cerebral oedema.
Patients initially show a high osmolar gap as they absorb the alcohol; thereafter, their osmolar gap falls and their anion gap rises as the ethylene glycol is metabolised to glycolic, glyoxylic and oxalic acids (see features section below). Antidotes are required to prevent this production of toxic metabolites (see management section below).
Early treatment with an antidote will minimise toxicity.
The fatal dose for a 70 kg adult is approximately 100 g of ethylene glycol (about 90 mL of pure ethylene glycol). Concentrations vary in different commercial products and are usually expressed as a percentage. Click
here for approximate amount of ethylene glycol in commercial preparations.
Inhalation and skin absorption are not serious hazards.
Ethylene glycol is rapidly absorbed from the gut. Peak concentrations occur 1 to 4 hours after ingestion.
Features
Typically, after a brief period of inebriation due to the intoxicating effect of ethylene glycol itself, metabolic acidosis develops, followed by tachypnoea, coma, convulsions, hypertension, the appearance of pulmonary infiltrates and oliguric renal failure. If untreated, death from multi-organ failure usually occurs 24 to 36 hours after ingestion.
The stages shown below may merge into each other; the time for each stage is only approximate.
Stage 1 (30 minutes to 12 hours after ingestion):
Apparent intoxication with alcohol (but no ethanol on breath), nausea, vomiting and haematemesis, coma and convulsions (often focal). Nystagmus, ataxia, ophthalmoplegia, papilloedema, hypotonia, hyporeflexia, myoclonic jerks, tetanic contractions and cranial nerve palsies (II, V, VII, VIII, IX, X, XII) may occur. Metabolic acidosis develops.
Stage 2 (12-24 hours after ingestion):
Increased respiratory rate, sinus tachycardia, hypertension, pulmonary oedema and congestive cardiac failure develop.
Stage 3 (24-72 hours after ingestion):
Flank pain, renal angle tenderness, acute tubular necrosis, hypocalcaemia (as a consequence of calcium complexing with oxalate), calcium oxalate monohydrate crystalluria, hyperkalaemia and hypomagnesaemia develop.
Calcium oxalate monohydrate crystalluria is diagnostic and hypocalcaemia is frequent. Leucocytosis is a common but a non-specific finding. Severe metabolic acidosis, hyperkalaemia, convulsions and coma carry a poor prognosis.
Metabolic changes:
Patients will develop a high osmolar gap as they absorb the toxic alcohol over the first few hours. Thereafter, as it is metabolised, the osmolar gap will fall while the patient's anion gap will climb and acidosis worsens. A severely poisoned patient can present early with a normal anion gap and a normal pH or hydrogen ion concentration. However, their osmolar gap will be high.
Absence of a high anion gap metabolic acidosis does not exclude the diagnosis if the presentation is early. Acidosis only develops after some of the toxic alcohol has been metabolised.
Absence of an elevated osmolar gap does not exclude serious poisoning since the osmolar gap begins to fall once the toxic alcohol is metabolised and may therefore not be elevated in the later stages of poisoning.
A high anion gap metabolic acidosis suggests that presentation is late and that a substantial amount of the toxic alcohol has been metabolised. The high anion gap usually occurs as the serum bicarbonate falls with progressive development of metabolic acidosis.
A high anion gap metabolic acidosis can occur after ingestion of any toxic alcohol (e.g. methanol; ethylene glycol; diethylene glycol) or with other clinical conditions (e.g. diabetic or alcoholic ketoacidosis, renal failure, multi-organ failure).
Although plasma lactate may be increased, some automated arterial blood gas analysers may erroneously report an elevated lactate which is in fact due to cross reactivity with metabolic products of the toxic alcohol.
Management
Early treatment with an antidote will prevent the production of toxic metabolites, severe acidosis and renal failure. Delay in commencing treatment with an antidote will result in a more severely poisoned patient.
Sertraline
Type of Product
Selective serotonin re-uptake inhibitor (SSRI). Used for the treatment of depressive illness, obsessive-compulsive disorder, post-traumatic stress disorder, panic disorder and social anxiety disorder.
Ingredients
Sertraline
Tablets - 25 mg, 50 mg, 100 mg, 150 mg, 200 mg
Concentrate for oral solution - 100 mg/5 mL
Toxicity
Fatalities are uncommon when sertraline is taken alone in overdose. However, deaths have occurred when other agents are co-ingested (Filter et al, 2007; Milner et al, 1998).
On the evidence available, sertraline has a wide margin of safety in overdose. In adults, overdoses of 700 mg to 2,100 mg have not resulted in serious symptoms. Ingestion of 4,000 mg resulted in convulsions in an adolescent. The largest known ingestion is 13.5 g with recovery reported. Another overdose of 2.5 g sertraline alone resulted in death (Zoloft SPC, 2017). Overdosage of 400 mg and 500 mg in two children have resulted in serotonin syndrome (Zoloft SPC, 2017).
An 11-year retrospective case study comparing the severity of SSRI exposures in children under 6-years found that of 13,358 sertraline exposures, only 3 developed major features (life-threatening or leading to significant residual disability) and 257 developed moderate symptoms (requiring treatment but not life-threatening). Of the remaining patients 1742 developed minor symptoms (transient, rapidly resolving) and the majority (11,355) none (Klein-Schwartz et al, 2012).
An 8-year-old female developed serotonin toxicity after ingestion of 1500 mg sertraline and required admission to ICU. She was discharged without any neurological sequelae (Grenha et al, 2013).
A 22-month-old female who ingested between 250 mg and 300 mg became lethargic but made a complete recovery (Catalano et al, 1998).
Peak plasma concentrations occur about 5 to 8 hours after ingestion. The plasma elimination half-life is about 26 hours (Sertraline SPC, 2022).
If taken with other serotonergic agents there is a greater risk of serotonin toxicity (serotonin syndrome).
Features
Clinical features may include GI upset, fever, tremor, agitation, diaphoresis, dizziness, dilated pupils, drowsiness, hallucinations, convulsions (these may be delayed) and coma.
Cardiovascular features include tachycardia, hypotension, hypertension, QT and QRS prolongation and Torsade de Pointes.
Rhabdomyolysis may occur late in the presentation and in the absence of convulsions. Other features include hepatotoxicity, hyponatraemia (due to SIADH) and hypoglycaemia.
Serotonin Toxicity
Serotonin toxicity may occur, especially in those exposed to multiple drugs affecting the serotonin system. Features include CNS effects (including agitation or coma), autonomic instability (including hyperpyrexia), and neuromuscular excitability (including clonus and raised CK).
Death of patients with serotonin toxicity may be due to hyperpyrexia with associated multi organ failure.
