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Palmitoylethanolamide for chronic, neuropathic and inflammatory pain.
PEA (palmitoylethanolamide) is an endogenous fatty acid amide produced by the body in response to tissue stress and inflammation. The supplemental form is a bioidentical version of the molecule. At biio., it is used as an adjunct for chronic pain, neuropathic pain, hEDS-related musculoskeletal pain, MCAS-related neuro-inflammatory symptoms, and post-viral pain and inflammation. It is also sometimes used as a sleep adjunct where pain is contributing to sleep disruption.
PEA is sold over the counter as a supplement in Australia and does not require a prescription. Bioavailability varies significantly between preparations. biio. recommends a micronised or ultra-micronised PEA preparation — these have particle sizes that significantly improve absorption compared with standard PEA powder.
PEA acts primarily on PPAR-alpha (peroxisome proliferator-activated receptor alpha) receptors, which modulate inflammatory gene expression. It also acts indirectly on cannabinoid pathways (without producing cannabinoid effects itself) and stabilises mast cells.
For the indications biio. uses it for, the relevant clinical effects are:
PEA is not an analgesic in the conventional sense. It does not block pain signalling directly. It modulates the inflammatory environment that drives chronic pain, which is why the effect is slow to emerge and cumulative.
Acts primarily on PPAR-alpha receptors, downregulating inflammatory cytokines and prostaglandins to reduce inflammatory pain.
Acts indirectly on cannabinoid pathways without producing cannabinoid effects itself, contributing to reduced neuropathic pain.
Stabilises mast cells, relevant in MCAS where neuro-inflammation contributes to symptoms.
Modulates microglial activation in the central nervous system, relevant for post-viral neuro-inflammatory symptoms.
PEA is sold as capsules, tablets, or sachets.
This is patient-led titration. You move up on schedule unless side effects cause you to pause.
Reducing the dose. PEA is well tolerated and dose reduction is rarely needed for side effects. If side effects appear, drop back to the previous tolerated dose.
With food, for 2 weeks
Increase after 2 weeks
1,200–1,800 mg total daily
If sedation, brain fog, or blood-pressure drops are bothersome, reduce by one step — 50 mcg — and hold there for 7 days before reassessing. Do not reduce more than one step at a time without biio. input.
Stopping the medication. PEA can be stopped without tapering. The anti-inflammatory benefit fades over 2–4 weeks after stopping; some patients keep it as a flare-management adjunct rather than a daily ongoing supplement.
If you miss a dose and it is still the same day, take it with the next meal. If it is already the next day, skip the missed dose. Do not double up. The cumulative effect is what matters; one missed dose does not undermine treatment.
PEA works slowly. The effect on pain usually emerges over 4–8 weeks of consistent dosing. The full effect on neuropathic pain, MCAS-related neuro-inflammation, and post-viral inflammatory symptoms may take 12 weeks to assess.
Trial for 12 weeks at 1200–1800 mg daily of a micronised preparation. Continue only if there is measurable change in pain scores, sleep, functional capacity, or your usual symptom diary. If after 12 weeks there has been no measurable change, contact biio. — the dose, the preparation, or the underlying mechanism may need reconsideration.
Most side effects are mild and settle as your body adapts. Use the three tiers below to decide what to do. When in doubt, lean toward the middle tier — call biio. and we will help.
Uncommon and usually self-limiting.
Usually a desirable effect for the sleep-disturbed pain population, but if excessive, take more of the daily dose in the morning and afternoon.
Take with more food. Split into smaller doses. Usually settles within 1–2 weeks.
(hives, facial swelling, throat tightening, difficulty breathing): stop immediately and call 000. Allergic reaction to PEA is uncommon but possible, particularly to capsule excipients.
all lower sodium or impair sodium regulation. Combining these with desmopressin increases the risk of hyponatraemia substantially. Inform biio. if you are on any of these medications.
DHEA is converted to oestradiol and testosterone in peripheral tissues. If you are also on oestrogen or progesterone (HRT, oral contraceptives), biio. will manage the dose carefully — sometimes a lower DHEA dose is appropriate.
Famotidine is primarily renally cleared. If eGFR is below 50, the dosing interval should be increased (e.g. 20 mg every 48 hours instead of daily). Inform biio. of any new kidney diagnosis.
Reduce fexofenadine absorption substantially. Take with water only; separate from juice by at least 2 hours.
Additive sedation. Avoid alcohol until you are on a stable dose and know its effect. Use other sedating medications with caution alongside cetirizine.
Additive blood pressure lowering. Combinations require blood pressure monitoring. Particular caution with beta blockers: if clonidine is stopped abruptly in someone also taking a beta blocker, rebound hypertension can be severe. If both are being discontinued, clonidine should be tapered first.
Case reports exist of CoQ10 affecting INR. If you take warfarin, have your INR checked within 1–2 weeks of starting or stopping CoQ10, and inform biio. and your anticoagulation clinician.
Creatine supplementation raises creatinine — a by-product of phosphocreatine breakdown — which can make kidney function tests appear worse even when the kidneys are not impaired. If you have known kidney disease or reduced eGFR, inform biio. before starting creatine — the decision to supplement requires clinical review, and baseline and follow-up creatinine may need monitoring.
No known significant interactions — all commonly co-prescribed at biio. Because cromolyn sodium is minimally absorbed from the gut, it has very few systemic drug interactions.
Alcohol inhibits DAO enzyme activity in the gut — both the DAO your body produces and supplemental DAO. Avoid alcohol if using DAO enzyme before a meal, as it directly reduces the supplement's effectiveness.
Additive potassium loss. This combination significantly increases hypokalemia risk. Inform biio. if another prescriber adds a diuretic.
Increase guanfacine exposure significantly. biio. may need to halve the dose during a course of these medications.
Do not combine with ivabradine. Antifungals: itraconazole, ketoconazole, voriconazole. Macrolide antibiotics: clarithromycin, telithromycin (note: azithromycin is usually acceptable — confirm with biio.). Calcium channel blockers: diltiazem and verapamil (not amlodipine — that is usually acceptable). Grapefruit juice increases ivabradine exposure significantly — avoid entirely while taking ivabradine. If a CYP3A4-inhibiting antibiotic is prescribed for an acute infection (e.g. clarithromycin for chest infection), discuss with biio. before starting — it may be necessary to temporarily stop ivabradine or choose an alternative antibiotic.
There is a theoretical interaction risk. If a new QT-prolonging drug is prescribed by another clinician, inform biio. before starting it. Do not combine without review.
These can mildly increase loratadine blood levels, but the clinical significance is low at standard doses. No dose adjustment is typically needed.
Increases aripiprazole exposure. Dose reduction may be needed during a course. Inform biio.
Do not combine unless you have discussed this with your prescriber. LDN will block their analgesic effect and may precipitate withdrawal symptoms. If another prescriber starts you on an opioid, ensure they are aware you are currently taking LDN. It is possible to use opioids and LDN together, however the timing needs to be discussed with your prescriber to ensure no interactions. Please note that if you decide to use 'party drugs', these may contain unknown opioid medications and it is advised not to mix these with LDN.
Binds to MT1 and MT2 receptors, combining with melatonin requires caution as excessive drowsiness can occur. If you take agomelatine, your melatonin dose should be very low (0.5 mg or less) and reviewed with biio. Do not take standard melatonin doses alongside agomelatine without clinical guidance.
Contraindicated. The combination can cause severe hypertensive crisis, headache, and cardiovascular collapse. Inform every prescriber that you take methyldopa. If an MAOI is prescribed, contact biio. immediately.
When prescribed together as combined hormone therapy, the progesterone is essential — it protects the uterine lining. Do not stop progesterone while continuing oestrogen.
Do not combine with midodrine. This combination can precipitate a severe hypertensive crisis. If an MAOI is prescribed by any clinician, inform biio. immediately on 1800 325 205.
Montelukast inhibits the CYP2C8 enzyme, which is involved in the metabolism of some medications. This is unlikely to be clinically significant for most biio. patients, but if you are prescribed a new medication — particularly ones broken down via cytochrome P450 pathways — inform biio.
Do not combine. The combined nicotine dose can produce toxicity. If you start a patch trial, you must not use any other nicotine product.
Nizatidine is renally cleared. If eGFR is significantly reduced, dose adjustment is needed. Inform biio. of any new kidney diagnosis.
Promotes renal sodium retention. When fludrocortisone and oral electrolyte supplementation are used together — as they commonly are in POTS management — the effect is additive. Your sodium and fluid targets need to be set with both in mind; taking standard electrolyte targets on top of fludrocortisone without clinical review increases the risk of fluid overload and oedema. Ensure biio. knows you are on both.
No clinically significant interaction documented. PEA does not have anti-platelet effects.
When prescribed together as combined hormone therapy, the progesterone is essential — it protects the uterine lining. Do not stop progesterone while continuing oestrogen.
Propranolol is contraindicated. If there is any history of asthma or bronchospasm, confirm with biio. before use.
Pyridostigmine significantly interacts with non-depolarising neuromuscular blocking agents, affecting their dose requirements and duration. You must inform your anaesthetist and surgical team that you take pyridostigmine before any procedure requiring general anaesthesia. Ideally, contact biio. in advance to discuss whether to pause pyridostigmine around the time of surgery.
Semaglutide slows gastric emptying, which may alter the absorption of some oral medications. Most medications are not clinically affected, but inform biio. of any narrow-window oral medication you take, such as ADHD medications.
Tirzepatide slows gastric emptying, which may alter the absorption of some oral medications. Most medications are not clinically affected, but inform biio. of any narrow-window oral medication you take.
Topical testosterone is often used alongside HRT in post-menopausal women. biio. will manage the regimen as a whole.
Also affects sodium and fluid retention. Both are sometimes used together in POTS management, but the combination increases risk of fluid overload and hyponatraemia — this combination requires clinical oversight. Do not combine without explicit biio. instruction.
DHEA can be converted to oestrogen and may interfere with the intended effect of these medications. Do not combine without specialist agreement.
Reflux medications such as esomeprazole, pantoprazole and omeprazole can be used with famotidine, however doses may need to be staggered. Discuss this with your biio. prescriber.
Reduce fexofenadine absorption. Separate by at least 2 hours.
High doses of theophylline can reduce cetirizine clearance, potentially increasing sedation. If theophylline is prescribed, inform biio.
These can reduce the blood pressure-lowering effect of clonidine. Inform biio. if a TCA is prescribed.
Statins reduce endogenous CoQ10 production in the liver. Supplemental CoQ10 is sometimes used alongside statins for this reason — there is no adverse pharmacokinetic interaction and the combination is safe.
These can reduce kidney clearance of creatinine. Combined use with creatine may produce more significant creatinine elevation on blood tests, which can confuse monitoring. Inform biio. if you use NSAIDs regularly.
Dosing should be reviewed if you develop significant kidney or liver disease, as elimination may be affected. Inform biio. of any new diagnoses.
May inhibit DAO activity in some people. Avoid very high-dose vitamin C supplementation if you are using DAO enzyme and not achieving expected benefit.
Both affect sodium and fluid balance. The combination requires clinical oversight and carries increased risk of fluid overload or electrolyte disturbance. Do not combine without explicit biio. instruction.
Reduce guanfacine effectiveness. May need higher doses of guanfacine.
Inform biio. and your pharmacist — dose reduction may be needed.
Ketotifen has additive sedating effects with other CNS depressants — alcohol, benzodiazepines, sleeping medications, opioids, and some antihistamines. Avoid alcohol until you know how ketotifen affects you. If combining with other sedating medications, do so with caution and only after discussion with biio.
Loratadine is non-sedating and does not significantly interact with alcohol — but alcohol itself is a histamine liberator and a common MCAS trigger. Use with awareness.
Increases aripiprazole exposure. Inform biio.
LDN may increase sensitivity to thyroid hormone in some people. If you take thyroid medication, monitor for signs of over-replacement — palpitations, tremor, sweating, anxiety — and report these to biio.
Dramatically increases melatonin blood levels — by up to 17-fold — by inhibiting the CYP1A2 enzyme that metabolises melatonin. If you take fluvoxamine, your melatonin dose should be very low (0.5 mg or less) and reviewed with biio. Do not take standard melatonin doses alongside fluvoxamine without clinical guidance.
Iron significantly reduces the absorption of methyldopa. Separate iron from methyldopa by at least 2 hours. Do not take together.
These accelerate progesterone metabolism and reduce its effect. Dose adjustment is sometimes needed — inform biio.
These drugs work in the opposite direction to midodrine — they dilate blood vessels. Combining them will reduce or negate midodrine's effect. Inform biio. if prescribed.
These drugs can reduce montelukast levels and reduce its effectiveness. If rifampicin or similar is prescribed, inform biio.
Nicotine increases caffeine metabolism — the same caffeine dose can feel less effective on a nicotine patch. The reverse can happen if you stop the patch — caffeine can feel stronger.
Reflux medications such as esomeprazole, pantoprazole and omeprazole can be used with nizatidine, however doses may need to be staggered. Discuss this with your biio. prescriber.
Reduces fluid excretion from the kidney. On days you take desmopressin, restrict fluid intake for 8 hours after the dose — even if you are otherwise on a high fluid intake target. Large fluid intake with desmopressin significantly increases the risk of hyponatraemia. See your desmopressin factsheet for the specific instructions that apply on dose days.
PEA is sometimes used to reduce reliance on NSAIDs. No direct interaction.
These accelerate progesterone metabolism and reduce its effect. Dose adjustment is sometimes needed — inform biio.
Combining with propranolol can cause severe bradycardia and heart block. Do not combine unless under the care of a cardiologist. (Amlodipine is generally safe.)
These directly oppose pyridostigmine's mechanism, reducing its effect. If an anticholinergic is prescribed, inform biio.
Absorption may be modestly reduced; thyroid function should be checked at standard intervals.
Manufacturer guidance suggests that for the first 4 weeks of starting tirzepatide and for 4 weeks after each dose increase, a barrier method or a non-oral contraceptive should be added to oral contraceptives, because tirzepatide may reduce oral contraceptive absorption during these windows. Confirm specific guidance with biio.
Testosterone may modestly affect coagulation parameters. INR monitoring may need to be more frequent on warfarin.
DAO and antihistamines work via entirely different mechanisms — DAO degrades histamine before absorption; antihistamines block histamine receptors after it reaches the bloodstream. The combination is rational and used at biio. There is no pharmacokinetic interaction.
Commonly co-prescribed for POTS at biio. No significant pharmacokinetic interaction, but combining haemodynamic agents increases the importance of monitoring blood pressure.
DHEA may modestly affect coagulation parameters. INR monitoring may need to be more frequent on warfarin.
Famotidine raises gastric pH and can reduce the absorption of atazanavir (HIV medication), ketoconazole, itraconazole taken as capsules, and certain oral iron preparations if taken within 2 hours. Separate these by at least 2 hours from famotidine if they are co-prescribed.
Cetirizine is primarily renally cleared. If your kidney function is significantly reduced (eGFR below 30), the dose should be halved to 5 mg daily or 10 mg every other day. Inform biio. of any new kidney diagnosis.
Additive sedation. Use with caution. Avoid alcohol until you are established on a stable dose and know its sedating effect.
CoQ10 has a mild blood-pressure-lowering effect in some people. If you take antihypertensives and your blood pressure is already on the lower side, monitor blood pressure when starting CoQ10 and report any significant further drop to biio.
High caffeine intake may partially reduce the performance benefit of creatine in some people. This is of limited clinical significance, but if you are a high caffeine user and not responding to creatine, it is worth considering reducing caffeine intake.
There are no foods that interact with cromolyn sodium directly. The four-times-daily meal-linked schedule is about timing of gut protection, not pharmacokinetic interaction.
These increase fexofenadine blood levels (by approximately 100%), but without increasing adverse effects at standard doses. No dose adjustment is typically required.
Hypokalemia from fludrocortisone can increase digoxin toxicity, potentially causing arrhythmias. If you take digoxin, strict potassium monitoring is required.
Additive blood pressure-lowering effect. If another clinician prescribes a blood pressure medication, inform biio.
Combining with ivabradine increases the risk of symptomatic bradycardia. Beta-blocker combinations require clinical oversight and regular pulse monitoring.
Commonly co-prescribed with ketotifen at biio. The combination does not produce a dangerous interaction, but additive sedation from hydroxyzine or first-generation antihistamines should be considered and you may be advised to time ketotifen separately.
Loratadine is metabolised by the liver. If you have significant liver impairment, a dose reduction to 10 mg every other day may be needed. Inform biio. of any new liver diagnosis.
Reduces aripiprazole exposure. Inform biio.
LDN's immune-modulating effects may interact unpredictably with immunosuppressants. Inform biio. and your prescribing specialist if you are on any of these.
Also inhibits CYP1A2 and increases melatonin levels. Short antibiotic courses with ciprofloxacin are common; if prescribed, take melatonin with caution and expect increased sedation or grogginess while on the antibiotic.
Both are central sympatholytics with additive effects. If both are co-prescribed, close monitoring is required. Do not adjust or stop either without biio. oversight.
Reduce progesterone levels significantly. Inform biio. if these are prescribed.
May increase midodrine levels and intensify side effects. If you are prescribed a new antidepressant or antimalarial (including prophylaxis), let biio. know.
These are commonly co-prescribed at biio. No clinically significant pharmacokinetic interactions with montelukast are expected.
Nicotine induces CYP1A2; stopping the patch increases drug levels of these substrates. Relevant only if any of these are co-prescribed — inform biio.
Nizatidine raises gastric pH and may reduce absorption of ketoconazole capsules, itraconazole capsules, atazanavir, and oral iron preparations if taken within 2 hours. Separate by at least 2 hours.
These counteract sodium retention and may reduce the benefit of electrolyte supplementation. If a diuretic is prescribed by another clinician, contact biio. — your electrolyte targets will likely need adjustment.
Often used together for neuropathic pain. No clinically significant pharmacokinetic interaction. The clinical effects are complementary.
Reduce progesterone levels significantly.
If both are being stopped, clonidine should be tapered off before propranolol is withdrawn. Withdrawing propranolol first while still on clonidine carries risk of rebound hypertension (high blood pressure) — discuss any planned cessation of either with biio.
Long-term co-use with cholinesterase inhibitors can cause significant muscle weakness in some patients. This is most relevant if oral corticosteroids are started long-term.
Potential for reduced absorption, particularly in the first 8-12 weeks of commencing GLP1. Do not rely on oral contraceptive pills for contraception.
Absorption may be modestly affected; thyroid function should be checked at standard intervals.
Testosterone may improve insulin sensitivity. Monitor for hypoglycaemia if you are on diabetes medication.
No clinically significant pharmacokinetic interactions with DAO enzyme supplement.
No significant interactions with desmopressin expected.
DHEA may modestly improve insulin sensitivity. Monitor for hypoglycaemia if you are on diabetes medication.
No clinically significant pharmacokinetic interactions with famotidine.
Most patients only need contact between scheduled reviews when one of the following applies. When in doubt, send a message — we would rather hear from you early.
For the tier-three emergencies above — rebound hypertension, collapse, overdose — call 000, not this line.