Why this poison is interesting

Every other page in this library is about a substance. This one is about an oxidation state. Nitrobenzene, aniline, dapsone, prilocaine, benzocaine, sodium nitrite and the alkyl nitrites have essentially nothing chemically in common, and they produce one indistinguishable illness — because what unites them is not their structure but a shared capacity to remove one electron from one iron atom. The library's other class-defined entry is sodium-channel blockade, which is grouped by a channel rather than a molecule; this is grouped by a redox reaction.

The mechanism is stated plainly by the UKHSA overview: "methaemoglobin forms when the iron component (Fe 2+) of haemoglobin is oxidised to the ferric (Fe 3+) state, which is unable to bind oxygen", and this "leads to reduction in the amount of oxygen available to tissues and can result in tissue hypoxia".¹ Haemoglobin is still present, still circulating, and still measured by every test that counts molecules rather than function.

The third reason — and the one that makes this page worth writing rather than folding into a sentence elsewhere — is the antidote. Methylthioninium chloride reverses the reaction, and its own UK label documents three separate problems with it: it is contraindicated in glucose-6-phosphate dehydrogenase deficiency², it produces methaemoglobinaemia at high doses², and it "may cause serious or fatal serotonergic syndrome" when combined with serotonergic drugs.² An antidote that causes the disease it treats, is forbidden in one of the populations most likely to need it, and carries a fatal-serotonin-syndrome warning against the commonest antidepressants is not a footnote.

A poison is a drug whose kinetics have escaped its pharmacology.

The toxic principle

Haemoglobin binds oxygen at a ferrous (Fe²⁺) iron held in a haem ring. The binding is reversible precisely because the iron stays ferrous throughout — oxygen is carried, not oxidised. Remove one electron and the iron becomes ferric (Fe³⁺), which cannot bind oxygen at all.¹ That single change accounts for the whole disease.

The body expects this to happen. "Under normal conditions low levels of methaemoglobin are continuously produced in the body", and the threshold for the pathological state is when methaemoglobin exceeds 1% of total haemoglobin.¹ The reduction of methaemoglobin back to haemoglobin is a continuous housekeeping process rather than an emergency response — which is why the clinical picture depends as much on the capacity of that process as on the size of the exposure.

There is a second, less appreciated component to the injury. Methaemoglobin does not merely fail to carry oxygen — its presence in a tetramer shifts the dissociation curve of the remaining ferrous subunits to the left, so they release what they are carrying less readily. The tissue is therefore worse off than the fraction of unusable haemoglobin alone would suggest. This page badges that as inference rather than as a quoted finding: it is standard haemoglobin physiology, and no source cited here states it. Inferred

Toxicokinetics

The kinetics that matter are of three different things: the parent compound, its metabolites, and the red cell's capacity to undo the reaction. The third is not a kinetic property of the poison at all, and it is often the one that decides the outcome.

Methaemoglobin inducers — where the poison's kinetics and the patient's enzymes both matter
Parameter	Therapeutic	In overdose	Why it changes
Absorption	Varies by agent: inhaled, ingested, or absorbed through skin	Nitrobenzene is absorbed by all routes¹	Dermal absorption is the route that surprises people, and it is why an industrial or domestic exposure with no ingestion history can still produce the illness.
Bioactivation	—	Required. For nitrobenzene, reduction and oxidation yield "nitrosobenzene, phenylhydroxylamine and aniline", and the methaemoglobinaemia is "caused by the metabolites"¹	The reason the illness is delayed rather than immediate. Compare the organophosphates, where bioactivation likewise means a falling parent concentration does not mean a falling toxic exposure.
Onset	—	"May be delayed for 1 to 4 hours depending upon the severity of exposure"¹	A short but real latent phase, and it is dose-dependent in the wrong direction for reassurance: a mild exposure declares later, so an asymptomatic patient at two hours is not yet cleared.
The opposing process	Continuous enzymatic reduction of methaemoglobin back to haemoglobin¹	Overwhelmed, or deficient, or both	The row that explains why identical exposures produce different illnesses. The label names the two enzyme systems whose failure matters: cytochrome b5 reductase and NADPH reductase, deficiency of either being a reason an antidote fails or is contraindicated.²
Age	—	Infants are more susceptible — foetal haemoglobin is "more susceptible to the formation of methaemoglobin" and "key metabolic enzymes able to clear methaemoglobin may not be fully developed"¹	Two independent hits in the same patient: more oxidisable substrate and less capacity to reverse it. The label separately cautions in newborns and infants below three months for the same reason.²
Ethanol	—	"Infants and those having consumed ethanol may be more susceptible"¹	Animal studies suggest increased sensitivity with concurrent ethanol, "although the toxicokinetic responsible for this effect have not been elucidated".¹ An observed interaction with an unexplained mechanism, stated as such.
Elimination	Urinary, with some faecal and exhaled loss¹	Slow. "Elimination of nitrobenzene is not considered to be rapid"; over 7 days to recover in some cases¹	The illness can outlast the exposure by a week, which means a single dose of antidote may not be the end of the problem — the compound is still there, making metabolites.
Dialysability	—	Never assessed. EXTRIP has published no recommendation covering these agents³	An absence that is misdirected rather than merely unasked. Even a dialyser that removed the parent compound perfectly would not reduce a single ferric iron back to ferrous — the poison at the point of illness is a modified molecule of the patient's own haemoglobin, and that is not removable.

Metabolism and the metabolites

This is the section where the class stops being a class. The agents differ entirely in how they reach the reaction and are identical in the lesion they produce — though not, as the antidote's label shows, in how they respond to treatment. Nitrobenzene needs two metabolic steps; sodium nitrite needs none; dapsone produces a hydroxylamine metabolite; the alkyl nitrites act directly. What follows uses nitrobenzene because it is the agent this page can source properly.

Nitrobenzene — a poison manufactured in two directions at once

NitrobenzeneNot itself the toxin. Absorbed by inhalation, ingestion and through skin¹
ReductionNitrosobenzene, phenylhydroxylamine, anilineThe metabolites that cause the methaemoglobinaemia¹
Ring oxidationNitrophenols, conjugated with glucuronide or sulphateThe detoxifying arm — "nitrophenol and aminophenol have been detected in the urine"¹
Fe(II) oxidised to Fe(III) — methaemoglobin"Unable to bind oxygen"¹. Above 1% of total haemoglobin this is methaemoglobinaemia¹
Cytochrome b5 reductase — the physiological routeHaemoglobin restoredContinuous housekeeping¹. Deficiency is one reason an antidote fails²
NADPH-dependent route — normally minor, and the one the antidote usesHaemoglobin restored, fasterRequires NADPH, which requires G6PD — the whole basis of the antidote's contraindication²
Functional anaemia and tissue hypoxia"Reduction in the amount of oxygen available to tissues... can result in tissue hypoxia"¹

Elimination and accumulation

Two things persist and they persist for different reasons. The compound persists — "elimination of nitrobenzene is not considered to be rapid", and in rats it took three days to eliminate 80% of a 22.5 mg/kg dose.¹ The illness persists because the compound is still being metabolised into the species that oxidises haem: "in some cases of nitrobenzene poisoning, it has taken individuals over 7 days to recover from the clinical signs of methaemoglobinaemia".¹

Two other reasons for apparent treatment failure are named on the antidote's own label, and both are diagnostic rather than pharmacological. "Failure to respond to methylthioninium chloride suggests cytochrome b5 reductase deficiency, glucose-6-phosphate dehydrogenase deficiency or sulfhaemoglobinemia. Alternative treatment options should be considered."² The third of those is a different disease wearing the same face — sulfhaemoglobin also produces cyanosis with a normal arterial oxygen tension and is not reversed by anything.

Where this latent phase sits among the others

Methaemoglobin inducers — paracetamol's cause at its shortest — one to four hours manufacturing the toxic species

The other 26 kinds of latent phase in this library

Amphetamines and MDMA — a hormone acting normally on a kidney behaving normally, while the patient supplies the water
Antipsychotics — a physical object in the stomach — extended-release quetiapine forming a pharmacobezoar
Arsenic — a tissue declaring on its own timetable rather than the poison's — the arsenic is excreted within days, but the nail that was growing while it circulated does not show its white transverse line for several weeks
Arsine and stibine — a red cell mass haemolysing faster than a kidney can cope with — the exposure is over, the haemolysis is silent until the urine changes colour, and the renal failure that follows is the cause of death
Beta-blockers — a repolarisation lesion waiting for an ectopic beat to fall inside it — sotalol prolongs the QT and then, for hours, nothing happens
Calcium-channel blockers — a tablet that has not yet dissolved
Carbon monoxide — an inflammatory process continuing after the poison itself has gone
Chlorine and ammonia — paraquat's cause at its shortest — the time an injured alveolar epithelium takes to leak
Cocaine — a package that has not yet failed — the calcium-channel blocker's cause moved outside the tablet, where wrapping integrity cannot be measured
Digoxin — distribution of the drug to its target — which that page argues is not a latent phase in the paracetamol sense at all
Ethylene glycol — paracetamol's cause with a different enzyme — glycolate accumulating behind glycolate oxidase while the patient looks merely drunk
GHB and GBL — not the poisoning but its withdrawal — a half-life under an hour means admission for any reason interrupts round-the-clock redosing
Hydrofluoric acid — an ion diffusing far enough to reach a nerve ending — and the thinner the solution, the further it travels before anybody feels it
Iron — a true remission — the corrosive injury settling while absorbed iron moves into the cells it will poison, so the patient improves on their way to the dangerous phase
Ketamine — nitrous oxide's cause on a longer clock — urothelial damage accumulating over months to years of repeated exposure
Lead — bone giving lead back — a store with a half-life of 10 to 30 years releasing its contents when pregnancy, lactation, menopause or osteoporosis resorbs it, so the blood concentration rises after the exposure has ended
Lithium — transport across cell membranes
Mercury — distribution on two clocks — tissue concentrations peaking within 24 hours everywhere except the brain, which is not reached until 2 to 3 days, and which then cannot let the poison out again
Methanol — paracetamol's cause again — formate accumulating behind a folate-dependent disposal step that primates perform poorly
Nitrous oxide — damage accumulating to a threshold
Opioids — an antidote wearing off before the poison does — renarcotisation, the only gap in this set that treatment creates rather than reveals
Organophosphate insecticides — a fat store emptying — and, separately, a second and unexplained lesion declaring itself at a neuromuscular junction the first phase had already left
Paracetamol — time spent manufacturing a toxic metabolite
Paraquat — the body responding to an injury that is already complete
Sodium-channel blockade — a gap that cannot be shortened
Thallium — hair on its own clock rather than the poison's — sensory symptoms come first and the alopecia that makes the diagnosis obvious follows them, well after the interval in which treatment is recommended

Target organs — and why those

There is only one target — the haemoglobin molecule — and the organ damage is entirely secondary to what that molecule stops doing. The cards below are therefore organised by which tissue notices first, and the answer is the familiar one: whatever cannot tolerate a fall in oxygen delivery.

The erythrocyte

TargetHaem iron, and the enzymes that keep it reduced

Why hereThe only primary target, and it is a molecule rather than an organ. Ferrous iron is oxidised to ferric, "which is unable to bind oxygen".¹ What determines whether this becomes an illness is the red cell's own reducing capacity — cytochrome b5 reductase physiologically, and the NADPH-dependent route that the antidote exploits.² The red cell is simultaneously the site of the poisoning and the site of its treatment. Established

At the bedsideChocolate-brown blood that does not turn red on exposure to air. Co-oximetry, not pulse oximetry, is what measures it — a standard pulse oximeter is not reading what it appears to be reading in this patient.

Brain

TargetNeurones dependent on continuous oxygen delivery

Why hereThe same reasoning as on every page in this band: the tissue with the highest oxygen demand and the least anaerobic reserve declares a delivery failure first. What is different here is that the delivery failure is invisible to every routine measure of oxygenation — the arterial oxygen tension is normal and the pulse oximeter is misleading. Established

At the bedsideHeadache, dizziness, fatigue and weakness early¹; then confusion, depressed consciousness and seizures as the fraction rises. A blue patient with a normal PaO2 and a falling GCS is this diagnosis until disproved.

Heart and circulation

TargetMyocardium, under a functional anaemia

Why hereThe heart responds to reduced oxygen-carrying capacity by increasing output, which increases its own oxygen demand — a compensation that costs more than it delivers when the carrying capacity itself is the problem. Patients with existing coronary disease or anaemia therefore decompensate at a lower methaemoglobin fraction than healthy ones. Inferred

At the bedsideTachycardia and tachypnoea early¹. Pre-existing anaemia matters twice over: fewer functional molecules to start with, and the same absolute loss represents a larger proportional one.

Skin and mucous membranes

TargetNot a target — a window

Why hereIncluded because it is the sign that makes the diagnosis and it is frequently misread. Methaemoglobin is dark and produces visible cyanosis at a far lower fraction than deoxyhaemoglobin does. Cyanosis here indicates a molecular abnormality, not a low arterial oxygen tension — the source describes "apparent cyanosis" at low methaemoglobin levels alongside fatigue, dizziness and headache.¹ Established

At the bedsideSlate-grey or blue discolouration, unresponsive to high-flow oxygen. The failure of cyanosis to improve on oxygen is the observation that should trigger co-oximetry.

Timeline of effects

Methaemoglobin inducers — a short manufacturing delay, then a long tail

Time

What you seeWhat is happening

0–1 hExposure and absorption
What you seeOften nothing. The patient may be entirely well.
What is happeningParent compound absorbed by inhalation, ingestion or through skin.¹ It is not yet the poison — the metabolites that oxidise haem have not been made.
1–4 hManufacture of the oxidising metabolite
What you seeThe latent interval. Onset "may be delayed for 1 to 4 hours depending upon the severity of exposure".¹
What is happeningReduction and oxidation of the parent compound to "nitrosobenzene, phenylhydroxylamine and aniline"¹ — the same shape of latent phase as paracetamol, and much shorter.
From ~1–4 hCyanosis appears
What you see"Apparent cyanosis, fatigue, dizziness headaches, with weakness tachypnoea, tachycardia at increasing levels."¹ The saturations do not improve on oxygen.
What is happeningMethaemoglobin exceeds the physiological 1%¹ and continues to rise while production outpaces enzymatic reduction. Arterial oxygen tension remains normal throughout.
HoursFunctional anaemia deepens
What you seeConfusion, depressed consciousness, arrhythmia and cardiovascular compromise as the fraction rises.
What is happeningProgressive loss of oxygen-carrying capacity, worsened by the leftward shift in the remaining ferrous subunits.Inferred The tissue insult is a delivery failure with a normal lung and a normal cardiac output.
After the antidoteResponse — or one of three reasons for none
What you seeRapid improvement in colour and consciousness where it works.
What is happeningMethylthioninium "in low concentration... speeds up the conversion of methaemoglobin to haemoglobin".² Failure to respond suggests cytochrome b5 reductase deficiency, G6PD deficiency or sulfhaemoglobinaemia² — or simply that the poison is still being metabolised.
DaysRelapse and slow resolution
What you seeRecurrence is expected with slowly eliminated agents. "Over 7 days to recover from the clinical signs of methaemoglobinaemia" in some nitrobenzene cases.¹
What is happening"Elimination of nitrobenzene is not considered to be rapid."¹ The antidote corrected the haemoglobin; it did nothing to the compound still making metabolites.

What the mechanism predicts at the bedside

Cyanosis that does not improve with high-flow oxygen is the whole diagnosis. The lung is fine; the carrier is broken.
The arterial oxygen tension will be normal, because it measures dissolved oxygen in plasma. A blood gas that looks reassuring is consistent with a severely ill patient here.
Pulse oximetry is not measuring what it appears to. Co-oximetry is the investigation, and asking for it requires having thought of the diagnosis first.
Chocolate-brown blood that does not redden in air is a bedside observation worth making deliberately.
The onset is delayed one to four hours¹, so a well patient shortly after exposure is not yet in the clear — and a milder exposure declares later, not sooner.
Ask about the last week, not the last hour, with slowly eliminated agents: recovery took over seven days in some nitrobenzene cases.¹
Expect relapse after a successful antidote response if the parent compound is still present. The antidote treats the haemoglobin, not the poison.
Infants are doubly susceptible — more oxidisable foetal haemoglobin and immature clearing enzymes¹ — and the antidote is separately cautioned below three months of age.²
Ask about G6PD deficiency before giving methylthioninium, which is contraindicated in it because of the risk of haemolytic anaemia.²
Ask about serotonergic drugs too. The label states methylthioninium "may cause serious or fatal serotonergic syndrome" with SSRIs, SNRIs, monoamine oxidase inhibitors and opioids including tramadol and fentanyl.²
Three named reasons for non-response: cytochrome b5 reductase deficiency, G6PD deficiency, or sulfhaemoglobinaemia.² Giving more is the wrong response to any of them, and more will itself produce methaemoglobinaemia.²
Dialysis has no role in the methaemoglobinaemia³ — the abnormality is in the patient's own haemoglobin, and no filter reduces a ferric iron. The antidote's own label mentions haemodialysis only for severe haemolysis after antidote overdose.²

The antidote, from the poison's side

Methylthioninium chloride is the most paradox-laden antidote in this library, and every one of the paradoxes is documented on its own UK marketing authorisation rather than inferred. Its licensed indication is the "acute symptomatic treatment of medicinal and chemical products-induced methaemoglobinaemia"² — precisely this page.

How it works: "In vivo, in low concentration, methylthioninium chloride speeds up the conversion of methaemoglobin to haemoglobin."² It acts as an electron shuttle, accepting electrons from NADPH and delivering them to ferric haem — recruiting a normally minor reducing pathway and making it the major one. Established Note the label's own qualifier: in low concentration.
Paradox one — it causes the disease: The label cautions that extreme care is needed in newborns and infants below three months "due to lower concentrations of NADPH-methaemoglobin reductase necessary for reducing methaemoglobin to haemoglobin, making these infants more susceptible to methaemoglobinaemia produced by high doses of methylthioninium chloride".² The antidote is itself an oxidant above the concentration at which it is a reductant — which is why in low concentration is doing so much work in the sentence above, and why more is not better here. Established
Paradox two — contraindicated in G6PD deficiency: Listed as a contraindication "due to the risk of haemolytic anaemia", alongside "deficiency in NADPH reductase".² The reasoning closes a loop: the antidote needs NADPH to work, G6PD generates NADPH, so a G6PD-deficient patient both fails to respond and is harmed by the attempt. And G6PD-deficient patients are among those most likely to develop methaemoglobinaemia from oxidant drugs in the first place. Established
Paradox three — it is a serotonergic drug: "Methylthioninium chloride may cause serious or fatal serotonergic syndrome when used in combination with serotonergic drugs. Avoid concomitant use... with selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors and opioids."² The interaction section names bupropion, buspirone, clomipramine, mirtazapine and venlafaxine, and "opioids, for example, tramadol, fentanyl, pethidine, and dextromethorphan".² An antidote whose own label lists the drugs on the SSRI and tramadol pages as contraindications is a genuine clinical problem, because oxidant drug exposure and antidepressant use are not rare in the same patient. Established
Two agents the label singles out by name: The class is not identical once the antidote is given, and the label says which agents differ. In aniline-induced methaemoglobinaemia "repeated doses of methylthioninium chloride may be required", with caution because it "may exacerbate Heinz body formation and haemolytic anaemia".² And methylthioninium "can exacerbate dapsone-induced haemolytic anemia because of the formation of the dapsone reactive metabolite hydroxylamine which oxidises haemoglobin".² The dapsone entry is this page's own relapse argument, named on the label for a specific agent: the parent drug goes on manufacturing an oxidising metabolite while the antidote reduces what it has already made. Both agents also carry a lower maximum cumulative dose, which is a dose and belongs to TOXBASE and NPIS rather than here. Established
When it does not work: "Failure to respond to methylthioninium chloride suggests cytochrome b5 reductase deficiency, glucose-6-phosphate dehydrogenase deficiency or sulfhaemoglobinemia. Alternative treatment options should be considered."² Three named diagnoses rather than a dose problem — and the instinct to repeat the dose is the one the first paradox punishes.
Oxygen: Does not correct the lesion and is given anyway: it maximises the dissolved fraction and the saturation of whatever functional haemoglobin remains. The same logic as in cyanide poisoning, and the same limitation.
Extracorporeal removal: Never assessed³ and mechanistically beside the point — the abnormality is an oxidation state of the patient's own haemoglobin.

Critical appraisal

The generalisation from nitrobenzene to a class is the page's largest methodological move. It is defensible — the terminal reaction genuinely is the same, and the page says explicitly that the agents differ entirely in how they reach it — but every kinetic statement here is nitrobenzene's, including the 1-to-4-hour onset and the over-7-day recovery.¹ Those must not be transported to dapsone, prilocaine or a nitrite without separate evidence, and this page does not supply it.
No evidence-tier downgrade appears on this page. No source found contests the ferrous-to-ferric mechanism or the antidote's action, and the antidote's three problems are stated on its own label rather than being contested claims — which makes them established facts about the drug, not doubts about a teaching. Badging them traditional would invert their meaning.
The leftward-shift argument is inference, badged as such, and is the page's one uncited mechanistic claim. It is standard haemoglobin physiology; no source cited here states it, and it needs either a citation or a lower tier.
The clinical table of methaemoglobin percentages was deliberately not printed. The source contains one, and its own footnote attributes it to TOXBASE¹ — which is login-gated, cannot be verified here, and from which nothing may be quoted. This is the exact shape of error that put a TOXBASE-only threshold on the paracetamol page during Band A, and it was caught this time before publication rather than after.
No treatment threshold appears anywhere on this page as a consequence of the point above. The fraction at which treatment is indicated is a TOXBASE and NPIS matter, and it is signposted rather than stated.
The interspecies factor of 5 is quoted with its source's own hedge: the variation "may be explained in part by" the reductase activity difference.¹ It is included because it warns against reading animal data optimistically, not as a conversion factor.
The ethanol interaction is reported exactly as the source frames it — an observation whose "toxicokinetic responsible for this effect have not been elucidated".¹ A mechanism was deliberately not invented for it.
The rat elimination figure (3 days for 80% of 22.5 mg/kg) is animal data and is labelled as such¹, and no human elimination half-life is quoted because none was available.
The heart card is inference and is the weakest on the page: the compensation-costs-more-than-it-delivers argument is physiological reasoning, not a finding.
EXTRIP's silence³ is uninformative here in an unusual way worth naming: even a perfect dialyser would not treat this poisoning, because the toxic species is a modified molecule of the patient's own haemoglobin rather than a circulating xenobiotic.

References

1
Nitrobenzene: toxicological overview. UK Health Security Agency, Compendium of Chemical Hazards. ("Methaemoglobin forms when the iron component (Fe 2+) of haemoglobin is oxidised to the ferric (Fe 3+) state, which is unable to bind oxygen. Under normal conditions low levels of methaemoglobin are continuously produced in the body. Methaemoglobinaemia occurs when the level of methaemoglobin is greater than 1% of total haemoglobin. This leads to reduction in the amount of oxygen available to tissues and can result in tissue hypoxia." "Nitrobenzene causes methaemoglobinaemia following acute exposure. Symptoms may develop within 1 to 4 hours post-exposure." "Low methaemoglobin levels cause apparent cyanosis, fatigue, dizziness headaches, with weakness tachypnoea, tachycardia at increasing levels." Metabolism "involves both reduction and oxidation pathways" yielding "nitrosobenzene, phenylhydroxylamine and aniline", with ring oxidation to nitrophenols; "the toxicological effects of nitrobenzene, methaemoglobinaemia, are caused by the metabolites". "Elimination of nitrobenzene is not considered to be rapid"; in rats "it took 3 days to eliminate 80% of a 22.5 mg/kg dose"; "in some cases of nitrobenzene poisoning, it has taken individuals over 7 days to recover from the clinical signs of methaemoglobinaemia". "Infants and those having consumed ethanol may be more susceptible"; foetal haemoglobin "more susceptible to the formation of methaemoglobin" and clearing enzymes "may not be fully developed"; ethanol effect noted "although the toxicokinetic responsible for this effect have not been elucidated". Interspecies: methaemoglobin reductase "5 times higher in rat erythrocytes than in human erythrocytes", with humans more sensitive. The document's Table 1 of clinical effects by methaemoglobin concentration is attributed in the source to TOXBASE and is deliberately not reproduced here.) gov.uk
2
Methylthioninium chloride Proveblue 5 mg/ml solution for injection — Summary of Product Characteristics. emc product 6898. (§4.1 "Acute symptomatic treatment of medicinal and chemical products-induced methaemoglobinaemia." §4.3 contraindicated in "patients with Glucose-6-phosphate dehydrogenase deficiency (G6PD) due to the risk of haemolytic anaemia" and in "deficiency in NADPH (nicotinamide adenine dinucleotide phosphate) reductase". §4.4 "Failure to respond to methylthioninium chloride suggests cytochrome b5 reductase deficiency, glucose-6-phosphate dehydrogenase deficiency or sulfhaemoglobinemia. Alternative treatment options should be considered." §4.4 "Methylthioninium chloride may cause serious or fatal serotonergic syndrome when used in combination with serotonergic drugs. Avoid concomitant use of methylthioninium chloride with selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors and opioids." §4.4 "Extreme caution should be exercised when administering to newborns and infants below the age of 3 months due to lower concentrations of NADPH-methaemoglobin reductase necessary for reducing methaemoglobin to haemoglobin, making these infants more susceptible to methaemoglobinaemia produced by high doses of methylthioninium chloride." §4.5 names bupropion, buspirone, clomipramine, mirtazapine, venlafaxine and "opioids, for example, tramadol, fentanyl, pethidine, and dextromethorphan". §5.1 "In vivo, in low concentration, methylthioninium chloride speeds up the conversion of methaemoglobin to haemoglobin.")
3
EXTRIP Workgroup — published recommendations index. Extracorporeal Treatments in Poisoning Workgroup. Cited for the absence of any recommendation covering nitrobenzene, aniline or the other methaemoglobin-forming agents. extrip-workgroup.org/recommendations

Methaemoglobin inducers

At a glance