Droxidopa interactions
Droxidopa (Northera), a sympathomimetic has 85 documented interactions across the FDA labels and fact sheets we index: 20 major, 51 moderate, 14 minor, and 0 where a label reports no significant interaction. Each entry below quotes the sentence behind it. This drug page is a starting point, not a verdict for your situation.
Major interactions (20)
Do Not Exceed Recommended Dose Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs in patients with asthma. (Albuterol label, Warnings and precautions)
- Budesonide and formoterolcorticosteroidMajor
Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. (Budesonide and formoterol label, Warnings and precautions)
- DronabinolcannabinoidMajor
Avoid concomitant use of other drugs that are also associated with similar cardiac effects (e.g., amphetamines, other sympathomimetic agents, atropine, amoxapine, scopolamine, antihistamines, other anticholinergic agents, amitriptyline, desipramine, other tricyclic antidepressants). (Dronabinol label, Warnings and precautions)
When LABA are used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone [see Serious Asthma-Related Events with Inhaled Corticosteroid/Long-acting Beta 2 -adrenergic Agonists] . (Fluticasone and salmeterol label, Warnings and precautions)
- Formoterolbeta-adrenergic agonistMajor
The increased risk of asthma-related death is considered a class effect of the long-acting beta 2 -adrenergic agonists, including formoterol fumarate inhalation solution. (Formoterol label, Warnings and precautions)
Should hypotension occur and a vasopressor be required, epinephrine must not be used since HALDOL DECANOATE may block its vasopressor activity, and paradoxically lower blood pressure. (Haloperidol label, Warnings and precautions)
- IsoniazidantibioticMajor
However, based on mechanism of action, the use of non-selective MAO inhibitors and linezolid should be avoided as there is a potential for increased blood pressure when taken with NORTHERA. (Droxidopa label, Drug interactions)
- Levalbuterolbeta-adrenergic agonistMajor
Do Not Exceed Recommended Dose Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs in patients with asthma. (Levalbuterol label, Warnings and precautions)
- LinezolidantibioticMajor
However, based on mechanism of action, the use of non-selective MAO inhibitors and linezolid should be avoided as there is a potential for increased blood pressure when taken with NORTHERA. (Droxidopa label, Drug interactions)
- Liothyroninethyroid hormoneMajor
• Larger doses may produce serious or even life-threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects [see Adverse Reactions (6) , Drug Interactions (7.7) , and Overdosage (10) ] . (Liothyronine label, Boxed warning)
- PhenelzineMAO inhibitorMajor
However, based on mechanism of action, the use of non-selective MAO inhibitors and linezolid should be avoided as there is a potential for increased blood pressure when taken with NORTHERA. (Droxidopa label, Drug interactions)
- Phentermine and topiramateCNS stimulantMajor
…(8.1) ] With glaucoma [see Warnings and Precautions (5.3) ] With hyperthyroidism Taking or within 14 days of stopping a monoamine oxidase inhibitors [see Drug Interactions (7) ] With known hypersensitivity to phentermine, topiramate or any of the excipients in phentermine and topiramate extended-release capsules, or idiosyncrasy to the sympathomimetic amines. (Phentermine and topiramate label, Contraindications)
Epinephrine Because of the potential for Promethazine to reverse epinephrine's vasopressor effect, epinephrine should NOT be used to treat hypotension associated with Promethazine Syrup overdose. (Promethazine label, Drug interactions)
- RasagilineMAO inhibitorMajor
However, based on mechanism of action, the use of non-selective MAO inhibitors and linezolid should be avoided as there is a potential for increased blood pressure when taken with NORTHERA. (Droxidopa label, Drug interactions)
- Salmeterolbeta-adrenergic agonistMajor
WARNING: ASTHMA-RELATED DEATH Long-acting beta 2 -adrenergic agonists (LABA), such as salmeterol, the active ingredient in SEREVENT DISKUS, as monotherapy (without inhaled corticosteroids [ICS]) increase the risk of asthma-related death. (Salmeterol label, Boxed warning)
- SelegilineMAO inhibitorMajor
However, based on mechanism of action, the use of non-selective MAO inhibitors and linezolid should be avoided as there is a potential for increased blood pressure when taken with NORTHERA. (Droxidopa label, Drug interactions)
- Terbutalinebeta-adrenergic agonistMajor
Hypersensitivity Terbutaline sulfate is contraindicated in patients known to be hypersensitive to sympathomimetic amines or any component of this drug product. (Terbutaline label, Contraindications)
Hypotension: monitor for signs and symptoms of hypotension, in particular in patients receiving concurrent antihypertensives; Zanaflex should not be used with other α 2 -adrenergic agonists ( 5.1 , 7.7 ) (Tizanidine label, Warnings and precautions)
- TranylcypromineMAO inhibitorMajor
However, based on mechanism of action, the use of non-selective MAO inhibitors and linezolid should be avoided as there is a potential for increased blood pressure when taken with NORTHERA. (Droxidopa label, Drug interactions)
- Umeclidinium and vilanterolanticholinergicMajor
• use of a long-acting beta 2 -adrenergic agonist (LABA), including vilanterol, one of the active ingredients in Umeclidinium and Vilanterol ELLIPTA, without an inhaled corticosteroid (ICS), in patients with asthma [see Warnings and Precautions ( 5.1 )] . (Umeclidinium and vilanterol label, Contraindications)
Moderate interactions (51)
- AclidiniumanticholinergicModerate
Sympathomimetics, Methylxanthines, Steroids In clinical studies, concurrent administration of aclidinium bromide and other drugs commonly used in the treatment of COPD including sympathomimetics (short-acting beta 2 agonists), methylxanthines, and oral and inhaled steroids showed no increases in adverse drug reactions. (Aclidinium label, Drug interactions)
- AmantadineanticholinergicModerate
Observe patients carefully when the dosage of NORTHERA is changed or when concomitant levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics. (Droxidopa label, Warnings and precautions)
• Hypotension: Slow the infusion; as needed, add vasopressor drugs, positive inotropic agents, and volume expansion. (Amiodarone label, Warnings and precautions)
- Amitriptylinetricyclic antidepressantModerate
When amitriptyline is given with anticholinergic agents or sympathomimetic drugs, including epinephrine combined with local anesthetics, close supervision and careful adjustment of dosages are required. (Amitriptyline label, Drug interactions)
- Amphetamine and dextroamphetamineCNS stimulantModerate
Tricyclic Antidepressants Clinical Impact May enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated. (Amphetamine and dextroamphetamine label, Drug interactions)
- AripiprazoleantipsychoticModerate
Observe patients carefully when the dosage of NORTHERA is changed or when concomitant levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics. (Droxidopa label, Warnings and precautions)
- AsenapineantipsychoticModerate
Observe patients carefully when the dosage of NORTHERA is changed or when concomitant levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics. (Droxidopa label, Warnings and precautions)
- BrexpiprazoleantipsychoticModerate
Observe patients carefully when the dosage of NORTHERA is changed or when concomitant levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics. (Droxidopa label, Warnings and precautions)
- Candesartanangiotensin II receptor blocker (ARB)Moderate
Very rarely, hypotension may be severe such that it may warrant the use of intravenous fluids and/or vasopressors. (Candesartan label, Warnings and precautions)
- Carbidopa and levodopadopaminergic drugModerate
Observe patients carefully when the dosage of NORTHERA is changed or when concomitant levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics. (Droxidopa label, Warnings and precautions)
- CariprazineantipsychoticModerate
Observe patients carefully when the dosage of NORTHERA is changed or when concomitant levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics. (Droxidopa label, Warnings and precautions)
- ChlorpromazineantipsychoticModerate
Observe patients carefully when the dosage of NORTHERA is changed or when concomitant levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics. (Droxidopa label, Warnings and precautions)
- ClozapineantipsychoticModerate
Observe patients carefully when the dosage of NORTHERA is changed or when concomitant levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics. (Droxidopa label, Warnings and precautions)
- DicyclomineanticholinergicModerate
…drugs including dicyclomine hydrochloride: amantadine, antiarrhythmic agents of Class I (e.g., quinidine), antihistamines, antipsychotic agents (e.g., phenothiazines), benzodiazepines, MAO inhibitors, narcotic analgesics (e.g., meperidine), nitrates and nitrites, sympathomimetic agents, tricyclic antidepressants, and other drugs having anticholinergic activity. (Dicyclomine label, Drug interactions)
- Digoxindigitalis glycosideModerate
Sympathomimetics Epinephrine Can increase the risk of cardiac arrhythmias. (Digoxin label, Drug interactions)
- Dorzolamide and timololcarbonic anhydrase inhibitorModerate
If necessary during surgery, the effects of beta-adrenergic blocking agents may be reversed by sufficient doses of adrenergic agonists. (Dorzolamide and timolol label, Warnings and precautions)
- EletriptantriptanModerate
Drugs that Increase Blood Pressure Administering NORTHERA in combination with other agents that increase blood pressure (e.g., norepinephrine, ephedrine, midodrine, and triptans) would be expected to increase the risk for supine hypertension. (Droxidopa label, Drug interactions)
- Esmololbeta blockerModerate
• Sympathomimetic drugs: Dose adjustment needed ( 7 ) (Esmolol label, Drug interactions)
- GlimepiridesulfonylureaModerate
…somatropin, protease inhibitors, atypical antipsychotic medications (e.g., olanzapine and clozapine), barbiturates, diazoxide, laxatives, rifampin, thiazides and other diuretics, corticosteroids, phenothiazines, thyroid hormones, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics (e.g., epinephrine, albuterol, terbutaline), and isoniazid. (Glimepiride label, Drug interactions)
- GlipizidesulfonylureaModerate
…olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), thyroid hormones, phenytoin, nicotinic acid, and calcium channel blocking drugs. (Glipizide label, Drug interactions)
- IloperidoneantipsychoticModerate
Observe patients carefully when the dosage of NORTHERA is changed or when concomitant levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics. (Droxidopa label, Warnings and precautions)
- Insulin aspartinsulinModerate
…Insulin Aspart Drugs: Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones. (Insulin aspart label, Drug interactions)
- Insulin degludecinsulinModerate
…Insulin Degludec Drugs: Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones. (Insulin degludec label, Drug interactions)
- Insulin detemirinsulinModerate
…Effect of LEVEMIR Drugs: Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones. (Insulin detemir label, Drug interactions)
- Insulin glargineinsulinModerate
…Glargine-yfgn Drugs: Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones. (Insulin glargine label, Drug interactions)
- Insulin lisproinsulinModerate
…Effect of LYUMJEV Drugs: Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones. (Insulin lispro label, Drug interactions)
- KetamineCNS depressantModerate
Sympathomimetics and Vasopressin : Sympathomimetics and vasopressin may enhance the sympathomimetic effects of ketamine [see Drug Interactions ( 7.2 )] . (Ketamine label, Warnings and precautions)
- Levothyroxinethyroid hormoneModerate
Sympathomimetics Concurrent use may of sympathomimetics and levothyroxine may increase the effects of sympathomimetics or thyroid hormone. (Levothyroxine label, Drug interactions)
- Lidocainelocal anestheticModerate
Concurrent administration of vasopressor drugs (for the treatment of hypotension related to obstetric blocks) and ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents. (Lidocaine label, Drug interactions)
- LisdexamfetamineCNS stimulantModerate
Tricyclic Antidepressants Clinical Impact May enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated. (Lisdexamfetamine label, Drug interactions)
- LumateperoneantipsychoticModerate
Observe patients carefully when the dosage of NORTHERA is changed or when concomitant levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics. (Droxidopa label, Warnings and precautions)
- LurasidoneantipsychoticModerate
Observe patients carefully when the dosage of NORTHERA is changed or when concomitant levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics. (Droxidopa label, Warnings and precautions)
- MethyldopaantihypertensiveModerate
If hypotension does occur during anesthesia, it usually can be controlled by vasopressors. (Methyldopa label, Drug interactions)
- Metolazonethiazide diureticModerate
Sympathomimetics Metolazone may decrease arterial responsiveness to norepinephrine, but this diminution is not sufficient to preclude effectiveness of the pressor agent for therapeutic use. (Metolazone label, Drug interactions)
- Midodrinealpha-adrenergic agonistModerate
Drugs that Increase Blood Pressure Administering NORTHERA in combination with other agents that increase blood pressure (e.g., norepinephrine, ephedrine, midodrine, and triptans) would be expected to increase the risk for supine hypertension. (Droxidopa label, Drug interactions)
- Nortriptylinetricyclic antidepressantModerate
Close supervision and careful adjustment of the dosage are required when Pamelor is used with other anticholinergic drugs and sympathomimetic drugs. (Nortriptyline label, Drug interactions)
- OlanzapineantipsychoticModerate
Observe patients carefully when the dosage of NORTHERA is changed or when concomitant levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics. (Droxidopa label, Warnings and precautions)
- PaliperidoneantipsychoticModerate
Observe patients carefully when the dosage of NORTHERA is changed or when concomitant levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics. (Droxidopa label, Warnings and precautions)
- PimavanserinantipsychoticModerate
Observe patients carefully when the dosage of NORTHERA is changed or when concomitant levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics. (Droxidopa label, Warnings and precautions)
- ProchlorperazineantipsychoticModerate
Observe patients carefully when the dosage of NORTHERA is changed or when concomitant levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics. (Droxidopa label, Warnings and precautions)
- Propranololbeta blockerModerate
Pharmacodynamic Drug-Drug Interactions Adrenergic Agonists: Beta-blockers may antagonize the antihypertensive effects of clonidine, and rebound hypertension may result if clonidine is withdrawn abruptly. (Propranolol label, Drug interactions)
- QuetiapineantipsychoticModerate
Observe patients carefully when the dosage of NORTHERA is changed or when concomitant levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics. (Droxidopa label, Warnings and precautions)
- RisperidoneantipsychoticModerate
Observe patients carefully when the dosage of NORTHERA is changed or when concomitant levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics. (Droxidopa label, Warnings and precautions)
- RizatriptantriptanModerate
Drugs that Increase Blood Pressure Administering NORTHERA in combination with other agents that increase blood pressure (e.g., norepinephrine, ephedrine, midodrine, and triptans) would be expected to increase the risk for supine hypertension. (Droxidopa label, Drug interactions)
- Sulfamethoxazole and trimethoprimsulfonamideModerate
Circulatory Shock Circulatory shock with fever, severe hypotension, and confusion requiring intravenous fluid resuscitation and vasopressors has occurred within minutes to hours of re-challenge with trimethoprim-sulfamethoxazole products in patients with history of recent (days to weeks) exposure to sulfamethoxazole and trimethoprim. (Sulfamethoxazole and trimethoprim label, Warnings)
- SumatriptantriptanModerate
Drugs that Increase Blood Pressure Administering NORTHERA in combination with other agents that increase blood pressure (e.g., norepinephrine, ephedrine, midodrine, and triptans) would be expected to increase the risk for supine hypertension. (Droxidopa label, Drug interactions)
- Sumatriptan and naproxentriptanModerate
Drugs that Increase Blood Pressure Administering NORTHERA in combination with other agents that increase blood pressure (e.g., norepinephrine, ephedrine, midodrine, and triptans) would be expected to increase the risk for supine hypertension. (Droxidopa label, Drug interactions)
- Timololbeta blockerModerate
If necessary during surgery, the effects of beta-adrenergic blocking agents may be reversed by sufficient doses of adrenergic agonists. (Timolol label, Warnings and precautions)
- TiotropiumanticholinergicModerate
Concomitant Respiratory Medications SPIRIVA RESPIMAT has been used concomitantly with short-acting and long-acting sympathomimetic (beta-agonists) bronchodilators, methylxanthines, oral and inhaled steroids, antihistamines, mucolytics, leukotriene modifiers, cromones, and anti-IgE treatment without increases in adverse reactions. (Tiotropium label, Drug interactions)
- ZiprasidoneantipsychoticModerate
Observe patients carefully when the dosage of NORTHERA is changed or when concomitant levodopa is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics. (Droxidopa label, Warnings and precautions)
- ZolmitriptantriptanModerate
Drugs that Increase Blood Pressure Administering NORTHERA in combination with other agents that increase blood pressure (e.g., norepinephrine, ephedrine, midodrine, and triptans) would be expected to increase the risk for supine hypertension. (Droxidopa label, Drug interactions)
Minor mentions (14)
- AcarboseantidiabeticMinor
These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel-blocking drugs, and isoniazid. (Acarbose label, Drug interactions)
- AspirinNSAIDMinor
(tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity [see Contraindications ( 4 )]. (Droxidopa label, Warnings and precautions)
- Aspirin and dipyridamoleantiplatelet agentMinor
(tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity [see Contraindications ( 4 )]. (Droxidopa label, Warnings and precautions)
- BenzonatateMinor
Severe reactions have required intervention with vasopressor agents and supportive measures. (Benzonatate label, Warnings)
- Empagliflozin and metforminSGLT2 inhibitorMinor
These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. (Empagliflozin and metformin label, Drug interactions)
- GlyburidesulfonylureaMinor
These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. (Glyburide label, Drug interactions)
- Glyburide and metforminsulfonylureaMinor
Examples: Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. (Glyburide and metformin label, Drug interactions)
- Insulin regular (human)insulinMinor
Atypical Antipsychotics (e.g., olanzapine and clozapine), Corticosteroids, Danazol, Diuretics, Estrogens, Glucagon, Isoniazid, Niacin, Oral Contraceptives, Phenothiazines, Progestogens (e.g., in oral contraceptives), Protease inhibitors, Somatropin, Sympathomimetic Agents (e.g., albuterol, epinephrine, terbutaline) and Thyroid Hormones. (Insulin regular (human) label, Drug interactions)
- IpratropiumanticholinergicMinor
ATROVENT HFA has been used concomitantly with other drugs, including sympathomimetic bronchodilators, methylxanthines, oral and inhaled steroids commonly used in the treatment of COPD. (Ipratropium label, Drug interactions)
- MetforminbiguanideMinor
Examples: Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. (Metformin label, Drug interactions)
- Pioglitazone and metforminthiazolidinedioneMinor
These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. (Pioglitazone and metformin label, Drug interactions)
- PropofolCNS depressantMinor
These effects are responsive to discontinuation of DIPRIVAN, intravenous fluid administration, and/or vasopressor therapy. (Propofol label, Warnings and precautions)
- RepaglinidemeglitinideMinor
…antipsychotics (e.g., olanzapine and clozapine), calcium channel antagonists, corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones. (Repaglinide label, Drug interactions)
- Sitagliptin and metforminDPP-4 inhibitorMinor
Examples: Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. (Sitagliptin and metformin label, Drug interactions)
Check Droxidopa against everything you take. Add your full list; every pair is checked at once.
Open in the checkerNot medical advice. Severity reflects the label's wording, not your circumstances. A "major" flag can be routine under supervision and a "minor" one can matter at high doses. Ask a pharmacist.