Medication

Clonidine

A centrally acting medication for the hyperadrenergic phenotype of POTS.

Medication
oral tablet
Target dose
100–200 micrograms
Titration
Clinician-led
Last reviewed
May 14, 2026

what it is.

01 — about

Clonidine is a centrally acting medication that reduces sympathetic nervous system activity. At biio., it is used primarily for the hyperadrenergic phenotype of POTS — where adrenaline surges, rising blood pressure on standing, tremor, or sudden-onset anxiety-like episodes are prominent features. It is also used to support sleep onset and, in this patient population, to reduce the nervous system overdrive that contributes to pain, cognitive difficulties, and difficulty settling at night.

Important

Do not stop clonidine abruptly.

how it works.

02 — mechanism

Clonidine stimulates alpha-2 adrenergic receptors in the brainstem, reducing the outflow of noradrenaline from the central nervous system. This lowers overall sympathetic tone — dampening the adrenergic surges that drive symptoms in the hyperadrenergic phenotype. It also increases nitric oxide production and reduces vascular reactivity, contributing to improved resting blood pressure stability. The calming effect on the nervous system supports sleep onset and reduces arousal.

ALPHA-2 STIMULATION

Acts on alpha-2 receptors in the brainstem — reducing noradrenaline outflow from the CNS.

LOWER SYMPATHETIC TONE

Dampens the adrenergic surges that drive hyperadrenergic POTS symptoms.

VASCULAR STABILITY

Increases nitric oxide and reduces vascular reactivity — improving resting BP stability.

SLEEP & AROUSAL

The calming effect supports sleep onset and reduces nervous-system arousal at night.

how to take it.

03 — daily routine

Clonidine is taken as an oral tablet. A transdermal patch formulation is available through paeditraic hospital pharmacies if daily tablets are not practical.

  • Take as directed — typically once nightly to start, with the option to add a morning or midday dose as the dose increases.
  • Do not take extra doses without instruction from biio.
  • Take at approximately the same time each day; consistency matters for avoiding rebound between doses.
  • Take with or without food.
  • Do not stop clonidine abruptly. See "Stopping the medication" below.
  • Store at room temperature.

starting & adjusting your dose.

04 — titration
clinician-led titrationadjust only on biio. instruction — never self-titrate

Starting dose and titration. This is clinician-led titration. Do not adjust your dose without instruction from biio.

  • Starting dose: 50 micrograms (0.05 mg) at night
  • Increase by 50 microgram increments every 3–7 days as directed by biio., based on symptom response and blood pressure
  • Target dose: typically 100–200 micrograms, given once or twice daily
  • Maximum dose: 200 micrograms (0.2 mg) twice daily. Higher doses or more frequent doses may be prescribed under close medical supervision.

Reducing the dose. If sedation, brain fog, or blood pressure drops are bothersome, reduce the dose by one step (50 micrograms) and hold at that level for 7 days before reassessing. Do not reduce more than one step at a time without biio. input.

Starting dose
50 micrograms (0.05 mg)

At night

Every 3 – 7 days
+50 micrograms

Every 3–7 days

Target dose
100–200 micrograms

Typically once or twice daily

Maximum
200 micrograms (0.2 mg)

Twice daily

Reducing the dose

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.

05 — tapering

Stopping the medication. Clonidine must be tapered, not stopped abruptly. Stopping suddenly can cause rebound hypertension and adrenergic surges — sometimes severe — as sympathetic activity rapidly increases once the drug is no longer present. The taper schedule depends on your current dose:

  • From 100 micrograms daily: reduce by 50 micrograms every 3–5 days
  • From 200 micrograms twice daily: reduce by 50 micrograms per dose every 5–7 days
  • Do not attempt to stop without a plan confirmed with biio.
Missed a dose?

If you miss a dose, take it as soon as you remember — provided it is within 2–3 hours of when you planned to take it. If it is close to your next dose, skip it and continue as normal. Do not double up. Note that missing clonidine doses can cause a brief rebound increase in heart rate and adrenergic symptoms between doses. If this is a recurring problem, discuss dose timing with biio.

what to expect.

06 — timeline & markers

Calmer autonomic responses, fewer sudden heart rate surges, improved sleep onset, and reduced anxiety-like episodes are the typical goals. Some sedation is expected, particularly at the start and when doses increase — this often reduces with continued use. Markers that suggest clonidine is working include:

  • Fewer sudden heart rate surges or panic-like episodes
  • Improved sleep onset
  • Reduced tremor or internal tension on standing
  • Lower resting heart rate

Effects on blood pressure should be monitored at home if possible. If orthostatic symptoms worsen (e.g. more dizziness on standing), this may mean clonidine is lowering blood pressure too much in your specific phenotype — contact biio.

side effects — what to do.

07 — three tiers

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.

01

common & usually self-manageable.

Manage at home
Mild blood pressure drop on standing

Some additional orthostatic drop may occur, particularly early in treatment. Continue compression garments and sodium/fluid intake.

Cognitive slowing or brain fog

Some people notice increased cognitive fatigue, particularly at higher doses. If this significantly affects function, reducing the dose is worth discussing with biio.

Dry mouth

Common. Frequent sips of water, sugar-free gum, or dry-mouth spray are helpful. Usually persists at some level throughout treatment.

Sedation and drowsiness

Most pronounced early in treatment and when doses increase. Do not drive until you know how a new dose affects your alertness. Usually improves over 1–2 weeks. If daytime sedation persists, discuss dose timing adjustment with biio.

02

worth a call to biio.

Contact us
Worsening brain fog

Brain fog is worsening and not improving after 2 weeks at a stable dose.

Needing to stop the medication urgently

You need to stop the medication urgently (for any reason) — biio. needs to provide a taper plan.

Heart rate consistently below 50 bpm

Heart rate consistently below 50 beats per minute.

Blood pressure below your usual baseline

Blood pressure dropping below your usual baseline or causing increased orthostatic symptoms.

Sedation lasting more than 2 weeks

Sedation lasting more than 2 weeks at a stable dose that is affecting driving, work, or daily activities.

03

seek urgent care.

Act immediately
Accidental overdose

Severe drowsiness, bradycardia, very low blood pressure: call 000 immediately. Do not give food or drink.

Loss of consciousness or sudden marked blood pressure drop

Call 000. Lie flat with legs elevated while waiting for assistance.

Severe hypertension after a missed or skipped dose

Sudden severe hypertension, severe headache, vision changes, or chest pain following a missed or skipped dose: these may indicate clonidine rebound. Call 000. Tell the treating team you take clonidine and when your last dose was.

Do not stop clonidine suddenly

If you must stop (e.g. if there is a severe side effect), taper as rapidly as safely possible while contacting biio. immediately.

interactions.

08 — what to flag
Medication or contextRuleWhat to know
Other medications that increase hyponatraemia risk
SSRIs/SNRIs, carbamazepine, some tricyclic antidepressants, NSAIDs, diuretics (frusemide, spironolactone, hydrochlorothiazide), and some antipsychotics
Inform biio.

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.

Oestrogen and progesterone therapy
Oversight

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.

Renal impairment
Inform biio.

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.

Fruit juices
grapefruit, orange, apple
Avoid

Reduce fexofenadine absorption substantially. Take with water only; separate from juice by at least 2 hours.

Alcohol and CNS depressants
benzodiazepines, sleeping medications, opioids
Caution

Additive sedation. Avoid alcohol until you are on a stable dose and know its effect. Use other sedating medications with caution alongside cetirizine.

Other blood pressure medications and antihypertensives
beta blockers, calcium channel blockers, ACE inhibitors, ARBs
Monitor

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.

Warfarin (anticoagulant)
Monitor

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.

Kidney disease
Oversight

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.

LDN, antihistamines, desmopressin, fludrocortisone, midodrine, ketotifen, montelukast
No issue

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
Avoid

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.

Potassium-depleting diuretics
frusemide, hydrochlorothiazide, chlorothiazide
Inform biio.

Additive potassium loss. This combination significantly increases hypokalemia risk. Inform biio. if another prescriber adds a diuretic.

CYP3A4 inhibitors
ketoconazole, itraconazole, ritonavir, clarithromycin, erythromycin, grapefruit juice
Oversight

Increase guanfacine exposure significantly. biio. may need to halve the dose during a course of these medications.

Strong CYP3A4 inhibitors
itraconazole, ketoconazole, voriconazole; clarithromycin, telithromycin; diltiazem and verapamil; grapefruit juice
Avoid

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.

QT-prolonging medications
including some antihistamines, antidepressants, antipsychotics, macrolide antibiotics, and antifungals
Inform biio.

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.

Ketoconazole, erythromycin, and other CYP3A4/2D6 inhibitors
No issue

These can mildly increase loratadine blood levels, but the clinical significance is low at standard doses. No dose adjustment is typically needed.

CYP3A4 inhibitors
ketoconazole, itraconazole, ritonavir, clarithromycin, erythromycin
Inform biio.

Increases aripiprazole exposure. Dose reduction may be needed during a course. Inform biio.

All opioid medications
codeine, oxycodone, morphine, tramadol, buprenorphine, fentanyl, and others
Avoid

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.

Agomelatine (an antidepressant used for depression, anxiety and sleep regulation)
Oversight

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.

MAO inhibitors (MAOIs)
Avoid

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.

Oestrogen
oral, transdermal, vaginal
Oversight

When prescribed together as combined hormone therapy, the progesterone is essential — it protects the uterine lining. Do not stop progesterone while continuing oestrogen.

MAO inhibitors (MAOIs)
phenelzine, tranylcypromine, selegiline, and the antibiotic linezolid
Avoid

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.

CYP2C8 inhibition
Inform biio.

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.

Other nicotine products
cigarettes, vapes, nicotine gum, nicotine lozenges, snus
Avoid

Do not combine. The combined nicotine dose can produce toxicity. If you start a patch trial, you must not use any other nicotine product.

Renal impairment
Inform biio.

Nizatidine is renally cleared. If eGFR is significantly reduced, dose adjustment is needed. Inform biio. of any new kidney diagnosis.

Fludrocortisone
Oversight

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.

Anticoagulants
warfarin, apixaban, rivaroxaban, dabigatran
No issue

No clinically significant interaction documented. PEA does not have anti-platelet effects.

Oestrogen
oral, transdermal, vaginal
Oversight

When prescribed together as combined hormone therapy, the progesterone is essential — it protects the uterine lining. Do not stop progesterone while continuing oestrogen.

Asthma and reactive airways disease
Avoid

Propranolol is contraindicated. If there is any history of asthma or bronchospasm, confirm with biio. before use.

Neuromuscular blocking agents used in anaesthesia
pancuronium, rocuronium, vecuronium
Plan ahead

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.

Oral medications generally
Inform biio.

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.

Oral medications generally
Inform biio.

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.

Oestrogen and progesterone therapy
Oversight

Topical testosterone is often used alongside HRT in post-menopausal women. biio. will manage the regimen as a whole.

Fludrocortisone
Oversight

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.

Tamoxifen and aromatase inhibitors
Avoid

DHEA can be converted to oestrogen and may interfere with the intended effect of these medications. Do not combine without specialist agreement.

Proton pump inhibitors
esomeprazole, pantoprazole, omeprazole
Plan ahead

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.

Aluminium- or magnesium-containing antacids
Plan ahead

Reduce fexofenadine absorption. Separate by at least 2 hours.

Theophylline
Inform biio.

High doses of theophylline can reduce cetirizine clearance, potentially increasing sedation. If theophylline is prescribed, inform biio.

Tricyclic antidepressants (TCAs)
amitriptyline, nortriptyline
Inform biio.

These can reduce the blood pressure-lowering effect of clonidine. Inform biio. if a TCA is prescribed.

Statins
atorvastatin, rosuvastatin, simvastatin
No issue

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.

NSAIDs (ibuprofen, naproxen) and diuretics
ibuprofen, naproxen
Inform biio.

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.

Renal or hepatic impairment
Inform biio.

Dosing should be reviewed if you develop significant kidney or liver disease, as elimination may be affected. Inform biio. of any new diagnoses.

High-dose vitamin C (ascorbic acid)
Caution

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.

Desmopressin
Oversight

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.

CYP3A4 inducers
carbamazepine, phenytoin, rifampicin, St John's wort
Oversight

Reduce guanfacine effectiveness. May need higher doses of guanfacine.

Moderate CYP3A4 inhibitors
fluconazole, some HIV medications
Inform biio.

Inform biio. and your pharmacist — dose reduction may be needed.

Sedating medications and alcohol
Caution

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.

Alcohol
Caution

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.

CYP2D6 inhibitors
fluoxetine, paroxetine, bupropion
Inform biio.

Increases aripiprazole exposure. Inform biio.

Thyroid hormone medication
thyroxine, T3, T3/T4 combinations
Monitor

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.

Fluvoxamine (an antidepressant used for OCD and anxiety)
Oversight

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.

Oral iron supplements
Plan ahead

Iron significantly reduces the absorption of methyldopa. Separate iron from methyldopa by at least 2 hours. Do not take together.

Anticonvulsants
phenytoin, carbamazepine, phenobarbital, oxcarbazepine, topiramate
Inform biio.

These accelerate progesterone metabolism and reduce its effect. Dose adjustment is sometimes needed — inform biio.

Alpha blockers
prazosin, terazosin, doxazosin, tamsulosin
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.

Rifampicin and other strong CYP enzyme inducers
Inform biio.

These drugs can reduce montelukast levels and reduce its effectiveness. If rifampicin or similar is prescribed, inform biio.

Caffeine
Caution

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.

Proton pump inhibitors
Plan ahead

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.

Desmopressin
Caution

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.

NSAIDs
No issue

PEA is sometimes used to reduce reliance on NSAIDs. No direct interaction.

Anticonvulsants
phenytoin, carbamazepine, phenobarbital, oxcarbazepine, topiramate
Inform biio.

These accelerate progesterone metabolism and reduce its effect. Dose adjustment is sometimes needed — inform biio.

Calcium channel blockers
verapamil and diltiazem
Avoid

Combining with propranolol can cause severe bradycardia and heart block. Do not combine unless under the care of a cardiologist. (Amlodipine is generally safe.)

Anticholinergic medications
bladder medications such as oxybutynin, solifenacin; some antidepressants; some antipsychotics
Inform biio.

These directly oppose pyridostigmine's mechanism, reducing its effect. If an anticholinergic is prescribed, inform biio.

Levothyroxine
Monitor

Absorption may be modestly reduced; thyroid function should be checked at standard intervals.

Oral contraceptives
Caution

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.

Anticoagulants
warfarin, apixaban, rivaroxaban, dabigatran
Monitor

Testosterone may modestly affect coagulation parameters. INR monitoring may need to be more frequent on warfarin.

Antihistamines (H1 and H2)
No issue

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.

Midodrine
Monitor

Commonly co-prescribed for POTS at biio. No significant pharmacokinetic interaction, but combining haemodynamic agents increases the importance of monitoring blood pressure.

Anticoagulants
warfarin, apixaban, rivaroxaban, dabigatran
Monitor

DHEA may modestly affect coagulation parameters. INR monitoring may need to be more frequent on warfarin.

Medications requiring acidic pH for absorption
atazanavir, ketoconazole, itraconazole capsules, certain oral iron preparations
Caution

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.

Renal impairment
Inform biio.

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.

CNS depressants
benzodiazepines, sleeping medications, opioids, alcohol
Caution

Additive sedation. Use with caution. Avoid alcohol until you are established on a stable dose and know its sedating effect.

Antihypertensives
Monitor

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.

Caffeine
Caution

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.

Food
No issue

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.

Erythromycin and ketoconazole
No issue

These increase fexofenadine blood levels (by approximately 100%), but without increasing adverse effects at standard doses. No dose adjustment is typically required.

Digoxin
Monitor

Hypokalemia from fludrocortisone can increase digoxin toxicity, potentially causing arrhythmias. If you take digoxin, strict potassium monitoring is required.

Other antihypertensives
Inform biio.

Additive blood pressure-lowering effect. If another clinician prescribes a blood pressure medication, inform biio.

Heart rate-slowing medications
beta-blockers, digoxin, amiodarone
Oversight

Combining with ivabradine increases the risk of symptomatic bradycardia. Beta-blocker combinations require clinical oversight and regular pulse monitoring.

H1 antihistamines
cetirizine, loratadine, fexofenadine, hydroxyzine
Caution

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.

Severe liver disease
Inform biio.

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.

CYP3A4 inducers
carbamazepine, phenytoin, rifampicin, St John's wort
Inform biio.

Reduces aripiprazole exposure. Inform biio.

Immunosuppressant medications
methotrexate, azathioprine, cyclosporin, mycophenolate
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.

Ciprofloxacin (an antibiotic)
Caution

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.

Clonidine
Oversight

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.

Rifampicin, rifabutin
Inform biio.

Reduce progesterone levels significantly. Inform biio. if these are prescribed.

Some antidepressants and antimalarials
Inform biio.

May increase midodrine levels and intensify side effects. If you are prescribed a new antidepressant or antimalarial (including prophylaxis), let biio. know.

LDN, antihistamines, desmopressin, fludrocortisone, midodrine, cromolyn sodium, ketotifen
No issue

These are commonly co-prescribed at biio. No clinically significant pharmacokinetic interactions with montelukast are expected.

Theophylline, clozapine, olanzapine, ropinirole, and other CYP1A2 substrates
Inform biio.

Nicotine induces CYP1A2; stopping the patch increases drug levels of these substrates. Relevant only if any of these are co-prescribed — inform biio.

Medications requiring acidic pH
Plan ahead

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.

Diuretics
frusemide, spironolactone, hydrochlorothiazide
Inform biio.

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.

Gabapentinoids
gabapentin, pregabalin
No issue

Often used together for neuropathic pain. No clinically significant pharmacokinetic interaction. The clinical effects are complementary.

Rifampicin, rifabutin
Inform biio.

Reduce progesterone levels significantly.

Clonidine
Plan ahead

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.

Corticosteroids
Caution

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.

Oral contraceptives
Caution

Potential for reduced absorption, particularly in the first 8-12 weeks of commencing GLP1. Do not rely on oral contraceptive pills for contraception.

Levothyroxine
Monitor

Absorption may be modestly affected; thyroid function should be checked at standard intervals.

Insulin and oral diabetes medication
Monitor

Testosterone may improve insulin sensitivity. Monitor for hypoglycaemia if you are on diabetes medication.

LDN, fludrocortisone, midodrine, desmopressin, cromolyn sodium, ketotifen, montelukast, and other standard biio. medications
No issue

No clinically significant pharmacokinetic interactions with DAO enzyme supplement.

LDN, antihistamines, montelukast, cromolyn sodium, ketotifen
No issue

No significant interactions with desmopressin expected.

Insulin and oral diabetes medication
Monitor

DHEA may modestly improve insulin sensitivity. Monitor for hypoglycaemia if you are on diabetes medication.

Loratadine, fexofenadine, cetirizine, nizatidine, LDN, ketotifen, montelukast, desmopressin, cromolyn sodium, fludrocortisone, midodrine
No issue

No clinically significant pharmacokinetic interactions with famotidine.

when to book a review.

09 — review triggers

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.

  • You want to stop clonidine for any reason — a taper plan is required and should be arranged before stopping.
  • A new cardiovascular, antidepressant, or sedating medication has been prescribed by another clinician.
  • Blood pressure monitoring shows a pattern that concerns you.
  • You are pregnant, planning pregnancy, or breastfeeding — clonidine crosses the placenta and use in pregnancy requires specialist oversight.
  • You have a planned surgical procedure — perioperative management needs specific planning.
  • Symptoms that clonidine was managing (adrenergic surges, sleep) have returned or worsened despite a stable dose.
Talk to biio.1800 325 205

For questions about your dose, side effects, or anything in this guide.

In an emergency

For the tier-three emergencies above — rebound hypertension, collapse, overdose — call 000, not this line.

Guide version
2
Last reviewed
May 14, 2026
Prepared bybiio. prescribing team

This guide supports day-to-day use of clonidine under the care of a biio. prescriber and does not replace individual clinical advice. Clonidine titration is clinician-led and it must never be stopped abruptly — if you are unsure about anything here, please contact biio. before making changes.