Carbaspirin calcium

What it is

Carbaspirin calcium is a calcium salt of acetylsalicylic acid, complexed with urea, sold mostly in Europe and in veterinary medicine and taken as an effervescent or soluble powder. It is listed by FDA as a permitted over-the-counter analgesic-antipyretic active ingredient. Once swallowed it is quickly broken down to acetylsalicylic acid and then to salicylic acid, so what reaches the bloodstream is aspirin and its metabolites. Doses are quoted as aspirin equivalents: 826.8 mg of effervescent calcium carbasalate is bioequivalent to 650 mg of aspirin.

What the research says

Pharmacologically this is aspirin delivered in a different salt. In 20 healthy volunteers it suppressed serum thromboxane B2 by 95.2% against 97.2% for aspirin, so the antiplatelet action is the same, and it produced significantly fewer gastric erosions at high bioequivalent doses. But the human outcome evidence is very thin: there is no large randomised trial of carbaspirin calcium on heart attacks, strokes or deaths. The one population study of low doses found the ulcer rate was not lower than aspirin's, and the only placebo-controlled trial we found at low dose, on altitude sickness, was null. The benefit claims therefore rest on short surrogate-endpoint studies and on the assumption that aspirin's outcome trials carry over.

Evidence grade: Limited evidence.

How it works

Drug class: Salicylate non-steroidal anti-inflammatory drug and antiplatelet agent; a urea-complexed calcium salt of acetylsalicylic acid

Carbaspirin calcium is a calcium salt of acetylsalicylic acid. After it is swallowed it is rapidly converted to acetylsalicylic acid, which is itself rapidly converted to salicylic acid. The acetylsalicylic acid then does what aspirin does: it permanently acetylates cyclo-oxygenase-1 in platelets, shutting down thromboxane production for the life of the platelet, and blocks the same enzyme in the stomach lining and elsewhere. (Source 1)

What it is used for

• FDA's over-the-counter monograph lists carbaspirin calcium as a permitted analgesic-antipyretic active with a full adult and paediatric dose schedule, so the use is a regulatory position dated 10.14.2022. We found no placebo-controlled analgesic trial of carbaspirin calcium by itself. Evidence: limited. (Source 2)
• One randomised double-blind double-dummy trial in 296 patients found calcium carbasalate equivalent to 900 mg aspirin plus metoclopramide 10 mg beat ergotamine plus caffeine for headache relief at 2 hours (54% vs 36%, p=0.003). It was an active-comparator trial with no placebo arm, and it tested a combination, not carbaspirin calcium alone. Evidence: limited. (Source 3)
• A 56-patient double-blind placebo-controlled trial found carbaspirin calcium at the equivalent of 325 mg aspirin daily significantly reduced platelet aggregation and serum thromboxane B2 within a day. These are surrogate measures; the trial was not powered for graft patency or clinical events, and the difference in patients with a rise in creatine kinase did not reach significance. Evidence: limited. (Source 4)
• A randomised controlled trial on Mt Kilimanjaro found low-dose calcium carbasalate at 380 mg a day had no preventive effect on acute mountain sickness and no effect on the prevalence or intensity of headache. Evidence: not-supported. (Source 5)
• At high bioequivalent doses in healthy volunteers it caused significantly fewer gastric erosions than aspirin. At low doses in a 19,819-person primary-care cohort the endoscopically confirmed peptic ulcer rate was not lower (4.31 vs 3.07 per 1000 person-years; adjusted hazard ratio 1.39, 95% CI 0.92-2.12). The two findings point in opposite directions. Evidence: disputed. (Source 6)

Interactions

• Alcohol (label): Carbaspirin calcium delivers acetylsalicylic acid, and FDA's professional labelling for aspirin says people drinking three or more alcoholic drinks a day should be counselled about bleeding risk. The monograph also requires the same stomach bleeding warning on carbaspirin calcium products. Limit: This is an aspirin statement applied to carbaspirin calcium on the grounds that it is metabolised to aspirin. No alcohol interaction study of carbaspirin calcium exists in the literature we reached. (Source 7)
• Warfarin and heparin (label): Salicylate displaces warfarin from protein binding, lengthening the prothrombin time and bleeding time, and increases heparin's effect. Adding aspirin to a vitamin K antagonist more than doubled intracranial haemorrhage in pooled randomised trials. Limit: Extrapolated from aspirin. One case report of carbasalate-induced angio-oedema records the patient being switched to acenocoumarol, but there is no carbasalate-anticoagulant interaction study. (Source 8)
• Methotrexate (label): Salicylate reduces the kidneys' clearance of methotrexate, which can raise methotrexate to bone-marrow-toxic levels, particularly in older people or people with impaired kidneys. This is a salicylate-class effect, so it applies to carbaspirin calcium. (Source 8)
• Other NSAIDs (label): Combining salicylates with other NSAIDs is to be avoided because it can increase bleeding or reduce kidney function. (Source 8)
• Acetazolamide (label): Aspirin and acetazolamide compete for renal tubular secretion, so acetazolamide levels can rise into the toxic range. This matters particularly because both have been tried together for altitude sickness; in the Kilimanjaro trial participants chose one or the other. (Source 8)
• Diuretics and ACE inhibitors (label): Salicylates inhibit renal prostaglandins, cutting renal blood flow and causing salt and fluid retention, which can blunt diuretics and ACE inhibitors in people with heart or kidney disease. (Source 8)
• Willow bark and other salicylate-bearing botanicals (theoretical): Willow bark supplements supply salicylate of their own and are not required to carry aspirin's warnings, so taking them alongside carbaspirin calcium adds to the same salicylate load. (Source 9)
• Ginkgo biloba (clinical trial): For aspirin itself, a randomised trial found 300 mg a day of Ginkgo biloba extract added to 325 mg of aspirin produced no detectable change in platelet function over four weeks. No equivalent study exists for carbaspirin calcium. Limit: Evidence is for aspirin, not carbaspirin calcium, and the trial was small and four weeks long. (Source 10)
• Calcium from the salt itself (theoretical): Carbaspirin calcium is a calcium salt, so each dose carries calcium with it. We could not find any study quantifying that calcium load or any interaction arising from it, so this is flagged as unquantified rather than asserted. Limit: The quoted source establishes only that the drug is a calcium salt. It gives no calcium content and reports no interaction; a reviewer should treat the calcium load as unmeasured in the literature we reached. (Source 1)

Stopping it

• We found no study of stopping or tapering carbaspirin calcium. The nearest evidence is a Swedish cohort of 601,527 long-term low-dose aspirin users in which discontinuation outside surgery or bleeding was associated with a more than 30% higher rate of cardiovascular events. Carbaspirin calcium is metabolised to aspirin, so the same logic plausibly applies, but this is an extrapolation from a different drug product and an observational design. (Source 11)
• There is no dependence or withdrawal syndrome to taper. FDA's professional labelling for aspirin, the drug carbaspirin calcium becomes in the body, records no addiction potential. (Source 12)

What goes wrong

Carbaspirin calcium users in that cohort developed peptic ulcers at 4.31 per 1000 person-years, against 3.07 on aspirin, a difference that was not statistically significant. (Source 13)

• Cohort study, Low certainty.
• Size: 7,928 effervescent calcium carbasalate users within a 19,819-person cohort; 115 ulcers in total.
• Who: primary-care users of low-dose salicylate in the Netherlands.
• How long: average 1.85 years.
• Result: 4.31 peptic ulcers per 1000 person-years during carbasalate use, versus 3.07 during acetylsalicylic acid use.
• Funding: not stated in the abstract.

Limit of this finding: The adjusted hazard ratio of 1.39 has a confidence interval running from 0.92 to 2.12, which includes 1, so this cohort did not show a real difference between the two drugs. The higher rate for carbaspirin calcium should not be read as evidence that it is worse. This is observational data, not a randomised comparison.

The risk for developing a peptic ulcer during drug use was: 3.07 per 1000 person-years for acetylsalicylic acid and 4.31 for effervescent calcium carbasalate. The risk of peptic ulcers was not statistically significantly higher in patients using effervescent calcium carbasalate than in acetylsalicylic acid users (adjusted hazard ratio, 1.39; 95% confidence interval, 0.92-2.12).

Carbaspirin calcium caused persistent two-sided periorbital angio-oedema in a 61-year-old man, confirmed by rechallenge with acetylsalicylic acid. (Source 14)

• Case report, Very low certainty.
• Size: one patient.
• Who: a 61-year-old man with xanthelasmata palpebrarum and chronic obstructive pulmonary disease who had been taking carbasalate calcium for two years.
• How long: swelling had been present for three years; resolved after the drug was replaced by acenocoumarol.
• Result: swelling and rhinoconjunctival symptoms resolved on withdrawal and recurred on provocation with acetylsalicylic acid.
• Funding: not applicable (case report)

Limit of this finding: A single case report, published in Dutch; no rate can be inferred from it.

Periorbital angio-oedema, a relatively uncommonly reported side effect of acetyl salicylic acid and its derivates, can occur even after previous long-term medication use.

Because carbaspirin calcium delivers acetylsalicylic acid, the salicylate class harms recorded for aspirin apply to it, and FDA's own list of these carries no frequencies. (Source 15)

• Official position, Certainty not rated.
• Size: not applicable.
• Who: people taking salicylates, per the monograph.
• How long: not applicable.
• Result: no rates are given; the monograph lists gastrointestinal bleeding, ulceration and perforation, intracranial haemorrhage, Reye's syndrome, hearing loss and tinnitus, anaphylaxis and renal failure among reported reactions.
• Funding: not applicable (regulatory document)

Limit of this finding: FDA's professional labelling text is written for aspirin; carbaspirin calcium is covered by the same monograph's labelling requirements for salicylate products. No carbaspirin-specific harm rates exist in the literature we reached apart from the ulcer rate in the Dutch cohort.

Gastrointestinal: Dyspepsia, GI bleeding, ulceration, perforation, nausea, vomiting, transient elevations of hepatic enzymes, hepatitis, Reye's Syndrome, pancreatitis.

FDA's monograph states in its professional labelling that even low doses of aspirin inhibit platelet function and lengthen bleeding time, which can harm people with inherited or acquired bleeding disorders. (Source 7)

• Official position, Certainty not rated.
• Size: not applicable.
• Who: over-the-counter users of salicylate analgesics.
• How long: not applicable.
• Result: no rates are given.
• Funding: not applicable (regulatory document)

Limit of this finding: This passage is the monograph's professional labelling for aspirin. Carbaspirin calcium is a different salt that delivers aspirin, and the monograph does not restate this warning for carbaspirin calcium by name, so read it as a statement about aspirin rather than as a measured finding about carbaspirin calcium. It is a regulatory position with no rates attached.

Coagulation Abnormalities: Even low doses of aspirin can inhibit platelet function leading to an increase in bleeding time. This can adversely affect patients with inherited (hemophilia) or acquired (liver disease or vitamin K deficiency) bleeding disorders.

What the evidence supports

At bioequivalent high doses, effervescent calcium carbasalate caused significantly fewer gastric erosions than aspirin while suppressing thromboxane just as much. (Source 6)

• Randomized trial, Low certainty.
• Size: 20 healthy volunteers in an endoscopist-blinded randomised crossover trial.
• Who: healthy volunteers given acetylsalicylic acid 650 mg three times daily and effervescent calcium carbasalate 826.8 mg three times daily.
• How long: two five-day treatment periods with endoscopy before and on day 5.
• Result: total gastric erosions 23.8 (16.1) on aspirin vs 9.1 (8.7) on carbasalate (p=0.004); gastric body Lanza score lower after carbasalate (p=0.003); visual analogue score 32.7 mm (20.8) vs 16.9 mm (15.9), p=0.008; serum salicylate 66 (23) mg/l vs 58 (17) mg/l (NS); thromboxane B2 inhibition 97.2 (3.5)% vs 95.2 (5.5)% (NS)
• Funding: not stated in the abstract.

Limit of this finding: Twenty volunteers, five days, erosions counted at endoscopy rather than clinical bleeding events, and at a 1,950 mg aspirin-equivalent daily dose far above any antiplatelet dose.

The total number of gastric erosions was 23.8 (16.1) in the ASA treated subjects compared with 9.1 (8.7) in ECC treated subjects (p = 0.004).

Carbaspirin calcium plus metoclopramide relieved acute migraine better than ergotamine plus caffeine, with fewer gastrointestinal side effects. (Source 3)

• Randomized trial, Low certainty.
• Size: 296 patients enrolled; 268 treated one attack and 235 treated two.
• Who: patients meeting International Headache Society criteria for migraine.
• How long: two acute attacks.
• Result: headache relief at 2 hours 54% vs 36% (p=0.003) for the first attack and 60% vs 44% (p=0.02) for the second; complete relief 20% vs 8% (p=0.006); gastrointestinal side effects 7% vs 21% (p=0.001); overall adverse events 22% vs 32% (p=0.075)
• Funding: not stated in the abstract.

Limit of this finding: No placebo arm, so this shows superiority over an old comparator, not that carbaspirin calcium works; and it tests a combination with metoclopramide, which is itself an anti-emetic used in migraine.

A superiority of CM over EC was observed for both treated attacks for the main endpoint: success in 54 versus 36%, p = 0.003 for the first attack and 60 versus 44%, p = 0.02 for the second attack.

Given immediately after coronary bypass surgery, carbaspirin calcium significantly reduced platelet aggregation and serum thromboxane B2 against placebo. (Source 4)

• Randomized trial, Low certainty.
• Size: 56 patients undergoing aorto-coronary bypass grafts (28 carbasalate, 28 placebo)
• Who: 50 men and 6 women, mean age 58.3 years, mostly triple-vessel disease.
• How long: single dose 6 hours after surgery then daily for 7 days.
• Result: significant reduction in platelet aggregation to arachidonic acid and collagen on day 1 (p=0.05) and day 7 (p<0.001) and to ADP on day 7 (p<0.01); serum thromboxane B2 reduced on day 1 (p<0.01) and day 7 (p<0.001); no significant difference in urinary 6-keto-PGF-1 excretion; fewer patients with a rise in creatine kinase but not significantly so.
• Funding: not stated in the abstract.

Limit of this finding: Surrogate endpoints only, 56 patients, 7 days; graft patency and clinical events were not measured.

A significant reduction in platelet aggregation to arachidonic acid and collagen on D1 (p = 0.05) and D7 (p < 0.001), and to ADP on D7 (p < 0.01) was observed in group C as compared with group P.

In broilers, carbaspirin calcium is rapidly broken down to acetylsalicylic acid and then to salicylic acid and gentisic acid. (Source 16)

• Animal study, Very low certainty.
• Size: broilers of body weight 2.0 (SD 0.3) kg given a single oral 40 mg/kg dose.
• Who: broiler chickens.
• How long: single dose with plasma sampling.
• Result: peak plasma concentrations of acetylsalicylic acid, salicylic acid and gentisic acid of 8.88, 42.6 and 10.1 mcg/mL at 0.170, 2.00 and 2.00 hours; terminal half-lives 11.2, 23.7 and 28.6 hours.
• Funding: not stated in the abstract.

Limit of this finding: Chickens, not people. This is the clearest published description of the metabolic route but it says nothing directly about human pharmacokinetics; we could not reach a human pharmacokinetic study of carbaspirin calcium.

In broilers, carbasalate calcium is quickly metabolized in ASA and ASA is rapidly converted to SA and one of the metabolites of SA is GA.

What the evidence does not support

In a 19,819-person cohort using low doses, carbaspirin calcium did not have a lower peptic ulcer rate than aspirin. (Source 13)

• Cohort study, Low certainty.
• Size: 19,819 subjects (11,891 on acetylsalicylic acid 80 mg, 7,928 on effervescent calcium carbasalate 100 mg); 115 ulcers.
• Who: incident users identified from the Dutch Integrated Primary Care Information database.
• How long: average 1.85 years of follow-up.
• Result: endoscopically confirmed peptic ulcer 3.07 per 1000 person-years on acetylsalicylic acid and 4.31 on effervescent calcium carbasalate; adjusted hazard ratio 1.39 (95% CI 0.92-2.12)
• Funding: not stated in the abstract.

Limit of this finding: Observational and not randomised; the confidence interval includes 1, so this neither shows carbasalate is worse nor confirms it is equivalent, and the point estimate is in the direction of more ulcers.

The risk of peptic ulcers was not statistically significantly higher in patients using effervescent calcium carbasalate than in acetylsalicylic acid users (adjusted hazard ratio, 1.39; 95% confidence interval, 0.92-2.12).

The authors of that cohort concluded that peptic ulcer rates are similar on low-dose carbaspirin calcium and on low-dose aspirin, which they attributed to a systemic rather than a local effect. (Source 17)

• Cohort study, Low certainty.
• Size: 19,819 subjects.
• Who: as above.
• How long: average 1.85 years.
• Result: incidence rate of peptic ulcer disease similar between the two drugs.
• Funding: not stated in the abstract.

Limit of this finding: This is an observational cohort, so it can show that the two drugs were followed by similar ulcer rates but cannot establish that either one caused the ulcers. The systemic-rather-than-local explanation is the authors' interpretation, not something the study measured directly.

The incidence rate of peptic ulcer disease is similar in patients using low-dose effervescent calcium carbasalate compared with regular low-dose acetylsalicylic acid.

Low-dose carbaspirin calcium did not prevent acute mountain sickness or reduce headache on a fast ascent of Kilimanjaro. (Source 5)

• Randomized trial, Very low certainty.
• Size: 15 received calcium carbasalate and 16 received placebo, out of 93 potential participants.
• Who: altitude-naive subjects attempting a fast climb of Mt Kilimanjaro (5,896 m), mean age 39 (SD 9), 15% female.
• How long: the climb; acute mountain sickness scored by Lake Louise Symptom Score and physician assessment.
• Result: calcium carbasalate 380 mg/day had no preventive effect on acute mountain sickness and no effect on prevalence or intensity of headache; event rate 84% in the pooled carbasalate-placebo group versus 55% on acetazolamide.
• Funding: not stated in the abstract.

Limit of this finding: Only 31 people in the randomised arms, with a non-randomised open acetazolamide arm chosen by participants, so selection bias is severe and the trial is far too small to exclude a modest effect.

Calcium carbasalate at 380 mg/day did not have any preventive effect on AMS and did not have any effect on the prevalence and intensity of headache.

Taking carbaspirin calcium in the morning rather than the evening made no difference to gastroduodenal tolerability or platelet inhibition. (Source 18)

• Randomized trial, Very low certainty.
• Size: 12 healthy volunteers in a randomised crossover trial.
• Who: healthy volunteers given effervescent calcium carbasalate equivalent to 160 mg aspirin once daily.
• How long: two 5-day periods with 21 days of washout, endoscopy by a single treatment-blinded endoscopist.
• Result: no difference between morning and evening administration on total lesion count at upper gastrointestinal endoscopy or on collagen-induced platelet aggregation; the drug almost totally inhibited platelet aggregation.
• Funding: not stated in the abstract.

Limit of this finding: Twelve volunteers for five days; the abstract gives no numbers at all for the lesion counts, only the statement of no difference, and prints 'agregation' for aggregation.

No difference was observed between morning and evening administration of ECC on gastroduodenal tolerability and platelet agregation.

Where the research disagrees

Whether carbaspirin calcium is kinder to the stomach than aspirin

• Murray and colleagues, Gut 1996, endoscopist-blinded randomised crossover trial, 20 healthy volunteers, high doses, erosion counts over 5 days: It is concluded that ECC causes significantly less gastroduodenal mucosal damage than ASA administered at bioequivalent doses as judged by serum salicylate, serum thromboxane, and mucosal PGE2 values. (Source 6)
• van Oijen and colleagues, Clinical Gastroenterology and Hepatology 2008, population-based cohort of 19,819 primary-care users at low doses, endoscopically confirmed ulcers over an average 1.85 years: The incidence rate of peptic ulcer disease is similar in patients using low-dose effervescent calcium carbasalate compared with regular low-dose acetylsalicylic acid. (Source 17)

How much

• Reference intake: Dose is set by the prescriber. As a dated position, FDA's over-the-counter monograph M013 (document dated 10.14.2022) gives an adult oral dosage of 414 to 828 mg every 4 hours, or 414 to 637 mg every 3 hours, or 828 to 1,274 mg every 6 hours while symptoms persist, with a separate schedule down to age 2. This is a regulatory dose range, not a recommendation to any reader. (Source 19)
• Upper limit: The same FDA monograph sets an adult ceiling of 5,096 mg in 24 hours, and ceilings of 3,105 mg for children 11 to under 12 years, 2,587.5 mg for 9 to under 11 years, 2,070 mg for 6 to under 9 years, 1,552.5 mg for 4 to under 6 years and 1,035 mg for 2 to under 4 years, with children under 2 told to consult a doctor. We found no toxicological upper limit established by study. The monograph's own arithmetic does not hold for the children's ceilings: 408.8 mg five times a day is 2,044 mg, not the 2,070 mg printed; 306.6 mg five times is 1,533 mg, not 1,552.5 mg; and 204.4 mg five times is 1,022 mg, not 1,035 mg. The figures are quoted as FDA prints them and have not been corrected here. (Source 19)
• Studied: Murray's crossover endoscopy trial gave effervescent calcium carbasalate 826.8 mg three times daily, stated as bioequivalent to 650 mg of aspirin, for five days. (Source 6)
• Studied: The migraine trial used calcium carbasalate equivalent to 900 mg aspirin with metoclopramide 10 mg. (Source 3)
• Studied: Berlin's tolerability crossover used effervescent calcium carbasalate equivalent to 160 mg aspirin once daily. (Source 18)
• Studied: The bypass-surgery trial used a dose equivalent to aspirin 325 mg daily for 7 days. (Source 4)
• Studied: The altitude trial used 380 mg of calcium carbasalate a day. (Source 5)
• Studied: The Dutch cohort compared effervescent calcium carbasalate 100 mg with acetylsalicylic acid 80 mg as bioequivalent low doses. (Source 1)

A common belief, and what the research shows

The belief: Carbaspirin calcium is a safer form of aspirin, so it is the sensible choice for anyone who needs long-term salicylate.

What the research shows: The gentleness claim comes from short volunteer endoscopy studies at high doses, where erosions were counted rather than bleeds: 23.8 erosions on aspirin against 9.1 on carbasalate over five days in 20 people. When the question was put at the low doses people actually take long term, in 19,819 primary-care patients followed for an average of 1.85 years, the endoscopically confirmed ulcer rate was not lower: 4.31 per 1000 person-years on carbasalate against 3.07 on aspirin, adjusted hazard ratio 1.39 (95% CI 0.92-2.12). The authors' explanation is that salicylate ulcers are caused systemically, not by the tablet touching the stomach wall, so changing the salt cannot fix them. There is also no large outcome trial of carbaspirin calcium on heart attacks, strokes or death at all, so its benefit is inferred from aspirin's trials rather than demonstrated.

Questions and answers

What is it?

Carbaspirin calcium is a calcium salt of acetylsalicylic acid, complexed with urea, usually taken as an effervescent or soluble preparation. FDA lists it as a permitted over-the-counter analgesic-antipyretic active ingredient alongside aspirin, buffered aspirin, choline salicylate, magnesium salicylate and sodium salicylate. It is also widely used in veterinary medicine. Doses are normally quoted as aspirin equivalents rather than in their own right. (Source 2)

What does it do in the body?

It is a delivery form for aspirin. After it is swallowed it is quickly converted to acetylsalicylic acid, which is itself rapidly converted to salicylic acid. The acetylsalicylic acid then permanently blocks cyclo-oxygenase-1 in platelets, so thromboxane production stops for the life of the platelet; in 20 volunteers it suppressed serum thromboxane B2 by 95.2% against aspirin's 97.2%, a difference that was not significant. The same enzyme blockade produces the pain and fever relief and the stomach harms. (Source 6)

Is it good or bad for you?

The honest answer is that the human outcome evidence for this specific salt is too thin to say. There is no trial of carbaspirin calcium on heart attacks, strokes or deaths. The positive findings are short and use surrogate measures: fewer gastric erosions than aspirin over five days in 20 volunteers, reduced platelet aggregation after bypass surgery in 56 patients, better migraine relief than ergotamine in 296 patients with no placebo arm. The negative findings are that at low doses it did not reduce peptic ulcers compared with aspirin, and that it did not prevent altitude sickness. Its harms are aspirin's harms, because it becomes aspirin. (Source 17)

How do you get more of it?

FDA's over-the-counter monograph permits carbaspirin calcium as an analgesic-antipyretic active and sets an adult oral dose range of 414 to 828 mg every 4 hours while symptoms persist. In practice it is mostly sold in continental Europe as an effervescent or soluble powder, and we could not reach a current US marketed product label for it on DailyMed. Antiplatelet dosing is a prescriber's decision. This is reported as a regulatory position, not as advice to any reader. (Source 19)

If it is harmful, what reduces it?

Carbaspirin calcium is cleared as salicylate, so overdose is managed as salicylate poisoning: supporting vital functions, increasing salicylate elimination and correcting the acid-base disturbance, with activated charcoal early, alkaline diuresis where kidney function allows, and dialysis in severe cases. For the unwanted effects of ordinary dosing, the only measure described in the literature we reached is stopping the drug: in the angio-oedema case report the swelling resolved once carbasalate calcium was withdrawn. (Source 20)

Why might someone be low in it or missing it?

The question does not apply in the nutrient sense; this is a manufactured drug, not something the body makes. People do not take it either because it has not been indicated, because it is not marketed where they live, or because they cannot take salicylates. The salicylate contraindications apply: known allergy to NSAIDs, the asthma-rhinitis-nasal-polyps syndrome, and children or teenagers with a viral illness because of Reye's syndrome. (Source 7)

Which whole foods contain it or feed it?

No whole food contains carbaspirin calcium; it is a synthesised salt. Salicylates themselves occur naturally in plants, and willow bark supplements deliver them: a United States Pharmacopeia safety review calculated that 240 mg of salicin from willow bark could yield 113 mg of salicylic acid. Residues of carbasalate calcium metabolites have been measured in animal foods because the drug is given to livestock, which is a food-chain question rather than a dietary source for people. (Source 9)

What happens if you do not have it?

Nothing happens to someone who never needed it. For someone established on long-term low-dose salicylate for vascular protection, the nearest evidence is from aspirin: in 601,527 Swedish users, stopping outside surgery or bleeding was associated with one extra cardiovascular event a year for every 74 people who stopped. That is observational and about aspirin, not about carbaspirin calcium. Where carbaspirin calcium was tested against placebo for a specific purpose and did nothing, as in altitude sickness, there is nothing to lose by not taking it. (Source 5)

How can you test for it?

There is no test for whether someone needs carbaspirin calcium. Its effect can be measured the way aspirin's is: serum thromboxane B2 and platelet aggregation tests were used in the volunteer and bypass-surgery trials, and serum salicylate concentrations were measured to confirm bioequivalence with aspirin (66 mg/l on aspirin versus 58 mg/l on carbasalate, not significantly different). Blood salicylate level is the measure used to judge the severity of poisoning. These are research and poisoning tools, not routine checks. (Source 6)

References

1. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. Peptic ulcerations are related to systemic rather than local effects of low-dose aspirin. (abstract, Background & Aims section). 2008. PMID 18242146, DOI 10.1016/j.cgh.2007.12.018. Read the source
2. US Food and Drug Administration; monograph document dated 10.14.2022. OTC Monograph M013: Internal Analgesic, Antipyretic, and Antirheumatic Drug Products for Over-the-Counter Human Use (Part B, Active ingredients, § M013.10). 2022. Read the source
3. European neurology. Comparative efficacy and safety of calcium carbasalate plus metoclopramide versus ergotamine tartrate plus caffeine in the treatment of acute migraine attacks. (abstract). 1999. PMID 9885327, DOI 10.1159/000007996. Read the source
4. Pathologie-biologie. [Antiaggregant effect and tolerance of calcium carbasalate administrated immediately after aorto-coronary bypass. Results of a double-blind versus placebo study]. (abstract). 1996. PMID 8977914. Read the source
5. High altitude medicine & biology. Low-dose acetylsalicylic acid analog and acetazolamide for prevention of acute mountain sickness. (abstract). 2008. PMID 18331216, DOI 10.1089/ham.2007.1037. Read the source
6. Gut. Comparison of effects of calcium carbasalate and aspirin on gastroduodenal mucosal damage in human volunteers. (abstract). 1996. PMID 8566836, DOI 10.1136/gut.38.1.11. Read the source
7. US Food and Drug Administration; monograph document dated 10.14.2022. OTC Monograph M013: Internal Analgesic, Antipyretic, and Antirheumatic Drug Products for Over-the-Counter Human Use (Professional labeling, Contraindications and Warnings). 2022. Read the source
8. US Food and Drug Administration; monograph document dated 10.14.2022. OTC Monograph M013: Internal Analgesic, Antipyretic, and Antirheumatic Drug Products for Over-the-Counter Human Use (Professional labeling, complete PRECAUTIONS section: General, Laboratory Tests, Drug Interactions, Carcinogenesis Mutagenesis Impairment of Fertility, Pregnancy, Labor and Delivery, Nursing Mothers, Pediatric Use). 2022. Read the source
9. Planta medica. United States Pharmacopeia Safety Review of Willow Bark. (abstract). 2019. PMID 31604354, DOI 10.1055/a-1007-5206. Read the source
10. Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. Effect of Ginkgo biloba (EGb 761) and aspirin on platelet aggregation and platelet function analysis among older adults at risk of cardiovascular disease: a randomized clinical trial. (abstract). 2007. PMID 17982321, DOI 10.1097/MBC.0b013e3282f102b1. Read the source
11. Circulation. Low-Dose Aspirin Discontinuation and Risk of Cardiovascular Events: A Swedish Nationwide, Population-Based Cohort Study. (abstract, Conclusions section). 2017. PMID 28947478, DOI 10.1161/CIRCULATIONAHA.117.028321. Read the source
12. US Food and Drug Administration; monograph document dated 10.14.2022. OTC Monograph M013: Internal Analgesic, Antipyretic, and Antirheumatic Drug Products for Over-the-Counter Human Use (Professional labeling, Drug Abuse and Dependence). 2022. Read the source
13. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. Peptic ulcerations are related to systemic rather than local effects of low-dose aspirin. (abstract, Results section). 2008. PMID 18242146, DOI 10.1016/j.cgh.2007.12.018. Read the source
14. Nederlands tijdschrift voor geneeskunde. [Periorbital swelling caused by carbasalate calcium]. (abstract). 2004. PMID 15366727. Read the source
15. US Food and Drug Administration; monograph document dated 10.14.2022. OTC Monograph M013: Internal Analgesic, Antipyretic, and Antirheumatic Drug Products for Over-the-Counter Human Use (Professional labeling, Adverse Reactions). 2022. Read the source
16. Journal of veterinary pharmacology and therapeutics. Analytical determination and pharmacokinetics of major metabolites of carbasalate calcium in broilers following oral administration. (abstract). 2011. PMID 21091728, DOI 10.1111/j.1365-2885.2010.01250.x. Read the source
17. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. Peptic ulcerations are related to systemic rather than local effects of low-dose aspirin. (abstract, Conclusions section). 2008. PMID 18242146, DOI 10.1016/j.cgh.2007.12.018. Read the source
18. Pathologie-biologie. [Comparison between effects of morning and evening administration of effervescent calcium carbasalate (equivalent of 160 mg aspirin) on the gastroduodenal mucosa in healthy volunteers]. (abstract). 1997. PMID 9309270. Read the source
19. US Food and Drug Administration; monograph document dated 10.14.2022. OTC Monograph M013: Internal Analgesic, Antipyretic, and Antirheumatic Drug Products for Over-the-Counter Human Use (§ M013.50(d) Directions, complete: the children-only dosage-unit example table and the consumer oral dosage schedules in paragraphs (1) to (6)). 2022. Read the source
20. US Food and Drug Administration; monograph document dated 10.14.2022. OTC Monograph M013: Internal Analgesic, Antipyretic, and Antirheumatic Drug Products for Over-the-Counter Human Use (Professional labeling, Overdosage). 2022. Read the source