Interactions between Combivent and Milnacipran
1 drug interaction and 27 additional warnings found for the following 2 drugs:
- Combivent (albuterol/ipratropium)
- milnacipran
Drug interactions
Moderate drug interactions
Moderate:
albuterol milnacipran
Applies to: Combivent (albuterol / ipratropium) and milnacipran
Monitor
Additive or synergistic effects on blood pressure and heart rate may occur when serotonin-norepinephrine reuptake inhibitors (SNRIs) are combined with sympathomimetic agents such as nasal decongestants, adrenergic bronchodilators, ophthalmic vasoconstrictors, and systemic vasopressors. The use of SNRIs alone has been associated with sustained increases in blood pressure and heart rate, and cases of elevated blood pressure requiring immediate treatment have been reported in postmarketing experience.
Management
Caution is advised if SNRIs are used with other drugs that can increase blood pressure and/or heart rate. Blood pressure and pulse should be measured prior to initiating SNRI therapy and monitored at regular intervals thereafter. Dose reduction or discontinuation of the SNRI should be considered in patients who experience a sustained increase in blood pressure or pulse rate.
References (6)
- (2001) "Product Information. Effexor (venlafaxine)." Wyeth-Ayerst Laboratories
- (2004) "Product Information. Cymbalta (duloxetine)." Lilly, Eli and Company
- (2008) "Product Information. Pristiq (desvenlafaxine)." Wyeth Laboratories
- (2009) "Product Information. Savella (milnacipran)." Forest Pharmaceuticals
- (2009) "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals
- (2013) "Product Information. Fetzima (levomilnacipran)." Forest Pharmaceuticals
Food/lifestyle interactions
Moderate food/lifestyle interactions
Moderate:
milnacipran Food/Lifestyle
Applies to: milnacipran
Generally avoid
Use of milnacipran in conjunction with chronic alcohol consumption may potentiate the risk of liver injury. Milnacipran alone can increase serum transaminase levels. In placebo-controlled fibromyalgia trials, increases in ALT were more frequently observed in patients treated with milnacipran 100 mg/day (6%) and 200 mg/day (7%) compared to patients treated with placebo (3%). One patient receiving milnacipran 100 mg/day (0.2%) had an increase in ALT greater than 5 times the upper limit of normal (ULN) but did not exceed 10 times the ULN. Increases in AST were also more frequently observed in patients treated with milnacipran 100 mg/day (3%) and 200 mg/day (5%) than in patients treated with placebo (2%). There have been reported cases of increased liver enzymes and severe liver injury, including fulminant hepatitis, from foreign postmarketing experience with milnacipran. Significant underlying clinical conditions and/or use of multiple concomitant medications were present in the cases of severe liver injury.
Management
Due to the risk of liver injury, patients prescribed milnacipran should be counseled to avoid excessive use of alcohol. Milnacipran should generally not be prescribed to patients with substantial alcohol use.
References (1)
- (2009) "Product Information. Savella (milnacipran)." Forest Pharmaceuticals
Moderate:
albuterol Caffeine
Applies to: Combivent (albuterol / ipratropium)
Monitor
Coadministration of two or more sympathomimetic or noradrenergic agents may increase the risk of nervousness, irritability, tachycardia, and/or increased blood pressure. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic and/or noradrenergic agents, including norepinephrine transporter inhibitors. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.
Management
Caution is advised if two or more sympathomimetic or noradrenergic agents are coadministered. Pulse and blood pressure should be closely monitored. Consultation with individual product labeling, as well as relevant institutional protocols, may be advisable for further guidance.
References (20)
- Rosenblatt JE, Lake CR, van Kammen DP, Ziegler MG, Bunney WE Jr (1979) "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res, 1, p. 45-52
- Cavanaugh JH, Griffith JD, Oates JA (1970) "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther, 11, p. 656
- (2001) "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc
- (2001) "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals
- (2001) "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals
- (2001) "Product Information. Focalin (dexmethylphenidate)." Mikart Inc
- (2024) "Product Information. Ephedrine (ephedrine)." Hameln Pharma Ltd
- (2023) "Product Information. Ephedrine Hydrochloride (ephedrine)." Wockhardt UK Ltd
- (2026) "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company
- (2025) "Product Information. Atomoxetine (atomoxetine)." Zentiva Pharma UK Ltd
- (2026) "Product Information. Atomoxetine (Apo) (atomoxetine)." Arrotex Pharmaceuticals Pty Ltd
- Angita Pharma, Inc (2026) AG-ATOMOXETINE Product Monograph (Health Canada) https://pdf.hres.ca/dpd_pm/00059014.PDF
- (2026) "Product Information. Boots Decongestant (Pseudoephedrine) (pseudoephedrine)." The Boots Company Plc
- (2023) "Product Information. Sinus and Nasal Decongestant (Trust) (pseudoephedrine)." Noumed Pharmaceuticals Pty Ltd
- (2019) "Product Information. Ephedrine (ephedrine)." Pfizer Australia Pty Ltd
- (2024) "Product Information. EPHEDrine Sulfate (ePHEDrine)." Amneal Pharmaceuticals LLC
- (2024) "Product Information. Lemsip Cough Max for Mucus Cough and Cold (guaifenesin/paracetamol/phenylephrine)." Reckitt Benckiser Healthcare (UK) Ltd
- emc (2026) Product information: sudafed plus blocked nose 1mg/50mg/ml nasal spray. https://www.medicines.org.uk/emc/product/14256/smpc?utm_source=chatgpt.com
- (2023) "Product Information. EPHEDrine Sulfate (ePHEDrine)." Baxter Corporation
- Neo Health (OTC) Pty Ltd (2026) Product information: pseudoephedrine hydrochloride-paracetamol capsules. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2024-PI-02603-1&d=20260804172310101&d=20260827172310101
Disease interactions
25 potential interactions Applies to: 18 conditions, including High Blood Pressure, Depression, Bipolar Disorder, Urinary Tract Infection, and Seizures.
Arrhythmia
Moderate:
Combivent
The ipratropium in Combivent has a moderate potential interaction with Arrhythmia.
Cases of supraventricular tachycardia and atrial fibrillation have been reported with the use of inhaled anticholinergic agents in patients with COPD/Asthma. Care and monitoring of cardiac function is recommended when prescribing these agents to patients at risk.
Bipolar Disorder
Major:
milnacipran
Milnacipran has a major potential interaction with Bipolar Disorder.
Adult and pediatric patients with depression and other psychiatric disorders may experience worsening of their symptoms and may have the emergence of suicidal thoughts and behavior. Patients should be monitored appropriately and observed closely for worsening of their symptoms, suicidality or changes in their behavior, especially during the first few months of treatment, and at times of dose changes. Discontinuing the medication should be considered if symptoms are persistently worse, or abrupt in onset. It may be prudent to refrain from dispensing large quantities of medication to these patients.
Moderate:
milnacipran
Milnacipran has a moderate potential interaction with Bipolar Disorder.
Therapy with SNRI antidepressants can cause activation of mania and hypomania and should be used with caution in patients with personal or family history of mania, hypomania, bipolar disorder, and other mood disorders.
Dehydration
Moderate:
milnacipran
Milnacipran has a moderate potential interaction with Dehydration.
Treatment with SNRI antidepressants can cause hyponatremia. Caution should be used when treating patients with hyponatremia or at greater risk of hyponatremia such as the elderly, patients taking diuretics or who are volume depleted.
Depression
Major:
milnacipran
Milnacipran has a major potential interaction with Depression.
Adult and pediatric patients with depression and other psychiatric disorders may experience worsening of their symptoms and may have the emergence of suicidal thoughts and behavior. Patients should be monitored appropriately and observed closely for worsening of their symptoms, suicidality or changes in their behavior, especially during the first few months of treatment, and at times of dose changes. Discontinuing the medication should be considered if symptoms are persistently worse, or abrupt in onset. It may be prudent to refrain from dispensing large quantities of medication to these patients.
Diabetes Mellitus
Moderate:
Combivent
The albuterol in Combivent has a moderate potential interaction with Diabetes Mellitus.
Adrenergic bronchodilators may cause increases in blood glucose concentrations. These effects are usually transient and slight, but may be significant with dosages higher than those normally recommended. Large doses of IV albuterol (not commercially available in the U.S.) and terbutaline sulfate have been reported to cause exacerbation of preexisting diabetes mellitus and ketoacidosis. Therapy with adrenergic bronchodilators should be administered cautiously in patients with diabetes mellitus. Closer monitoring of blood glucose concentrations may be appropriate. Systemic adverse effects are minimized, but not abolished, by administration of these agents via oral inhalation.
Glaucoma, Narrow Angle
Moderate:
Combivent
The ipratropium in Combivent has a moderate potential interaction with Glaucoma, Narrow Angle.
Aclidinium, ipratropium, umeclidinium, and tiotropium are anticholinergic agents. Although systemic effects are uncommon due to the poor absorption of quaternary ammonium compounds from gastrointestinal and nasal mucosa, worsening of urinary retention or angle-closure glaucoma has been reported. Increased intraocular pressure and precipitation or exacerbation of angle-closure glaucoma may also occur due to inadvertent contact of the eye with aerosolized or nebulized drug. Accordingly, therapy with quaternary ammonium compounds should be administered cautiously in patients with urinary retention/obstruction or angle-closure glaucoma. Measures should be taken whenever possible to minimize ocular exposure to these drugs, such as keeping eyes closed during oral inhalation or use of a mouthpiece rather than face mask during nebulization. Patients should be advised to contact their physician if they experience urinary difficulty (especially in patients with prostatic hyperplasia or bladder neck obstruction); or signs and symptoms of angle-closure glaucoma (e.g., eye pain or discomfort; blurred vision; visual halos; colored images in association with red eyes from conjunctival congestion or corneal edema).
Moderate:
milnacipran
Milnacipran has a moderate potential interaction with Glaucoma, Narrow Angle.
SNRI antidepressants cause pupillary dilation that may trigger an angle closure attack in patients with anatomically narrow angle without iridectomy.
Heart Disease
Moderate:
Combivent
The albuterol in Combivent has a moderate potential interaction with Heart Disease.
Adrenergic bronchodilators can stimulate cardiovascular beta- 1 and beta- 2 receptors, resulting in adverse effects such as tachycardia, palpitation, peripheral vasodilation, blood pressure changes, and ECG changes (e.g., flattening of the T wave; prolongation of the QT interval; ST segment depression). Direct stimulation of cardiac tissues is mediated by beta- 1 receptors and thus less likely to occur with beta-2-selective agents such as albuterol. However, beta-2-selectivity is not absolute and can be lost with larger doses. High dosages of these agents have been associated with precipitation or aggravation of angina, myocardial ischemia, and cardiac arrhythmias. Therapy with adrenergic bronchodilators should be administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism, and/or underlying cardiovascular disorders such as coronary insufficiency, cardiac arrhythmias, or hypertension. The recommended dosages should not be exceeded.
High Blood Pressure
Moderate:
Combivent
The albuterol in Combivent has a moderate potential interaction with High Blood Pressure.
Adrenergic bronchodilators can stimulate cardiovascular beta- 1 and beta- 2 receptors, resulting in adverse effects such as tachycardia, palpitation, peripheral vasodilation, blood pressure changes, and ECG changes (e.g., flattening of the T wave; prolongation of the QT interval; ST segment depression). Direct stimulation of cardiac tissues is mediated by beta- 1 receptors and thus less likely to occur with beta-2-selective agents such as albuterol. However, beta-2-selectivity is not absolute and can be lost with larger doses. High dosages of these agents have been associated with precipitation or aggravation of angina, myocardial ischemia, and cardiac arrhythmias. Therapy with adrenergic bronchodilators should be administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism, and/or underlying cardiovascular disorders such as coronary insufficiency, cardiac arrhythmias, or hypertension. The recommended dosages should not be exceeded.
Moderate:
milnacipran
Milnacipran has a moderate potential interaction with High Blood Pressure.
Selective serotonin and norepinephrine reuptake inhibitor antidepressants (SNRIs) have been associated with sustained increases in blood pressure. Therapy with SNRI antidepressants should be administered cautiously in patients with preexisting hypertension. Blood pressure should be assessed prior to initiating treatment and monitored regularly. The dose should be reduced or discontinued if necessary.
Hyperthyroidism
Moderate:
Combivent
The albuterol in Combivent has a moderate potential interaction with Hyperthyroidism.
Adrenergic bronchodilators can stimulate cardiovascular beta- 1 and beta- 2 receptors, resulting in adverse effects such as tachycardia, palpitation, peripheral vasodilation, blood pressure changes, and ECG changes (e.g., flattening of the T wave; prolongation of the QT interval; ST segment depression). Direct stimulation of cardiac tissues is mediated by beta- 1 receptors and thus less likely to occur with beta-2-selective agents such as albuterol. However, beta-2-selectivity is not absolute and can be lost with larger doses. High dosages of these agents have been associated with precipitation or aggravation of angina, myocardial ischemia, and cardiac arrhythmias. Therapy with adrenergic bronchodilators should be administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism, and/or underlying cardiovascular disorders such as coronary insufficiency, cardiac arrhythmias, or hypertension. The recommended dosages should not be exceeded.
Hypokalemia
Moderate:
Combivent
The albuterol in Combivent has a moderate potential interaction with Hypokalemia.
Adrenergic bronchodilators may cause decreases in serum potassium concentrations, primarily when given by nebulization or intravenous administration. Although this effect is usually transient and does not require supplementation, clinically significant hypokalemia may occur in some patients, with the potential to induce cardiovascular adverse effects. The relevance of these observations to oral or oral aerosol/powder for inhalation therapy is unknown. Therapy with adrenergic bronchodilators should be administered cautiously in patients with or predisposed to hypokalemia.
Hyponatremia
Moderate:
milnacipran
Milnacipran has a moderate potential interaction with Hyponatremia.
Treatment with SNRI antidepressants can cause hyponatremia. Caution should be used when treating patients with hyponatremia or at greater risk of hyponatremia such as the elderly, patients taking diuretics or who are volume depleted.
Liver Disease
Major:
milnacipran
Milnacipran has a major potential interaction with Liver Disease.
Postmarketing studies have reported that duloxetine and some other SNRIs like milnacipran may aggravate preexisting liver disease. The use of duloxetine delayed-release and milnacipran should be avoided in patients with chronic liver disease or cirrhosis.
Moderate:
Combivent
The ipratropium in Combivent has a moderate potential interaction with Liver Disease.
Ipratropium has not been studied in patients with hepatic or renal insufficiency. Therapy with this agent should be used with caution in these patients.
Mania
Moderate:
milnacipran
Milnacipran has a moderate potential interaction with Mania.
Therapy with SNRI antidepressants can cause activation of mania and hypomania and should be used with caution in patients with personal or family history of mania, hypomania, bipolar disorder, and other mood disorders.
Renal Dysfunction
Major:
milnacipran
Milnacipran has a major potential interaction with Renal Dysfunction.
The clearance of SNRI antidepressants is decreased in subjects with renal impairment. SNRIs should be used with caution in this group of patients and a dose adjustment is recommended in those with moderate and severe renal impairment. The use of SNRIs is not recommended in patients with end-stage renal disease.
Moderate:
Combivent
The albuterol in Combivent has a moderate potential interaction with Renal Dysfunction.
Levalbuterol is substantially excreted by the kidney, and the risk of toxic reactions may be greater in patients with impaired renal function. Care should be taken in dose selection in patients with renal impairment and it may be useful to monitor renal function.
Moderate:
Combivent
The ipratropium in Combivent has a moderate potential interaction with Renal Dysfunction.
Ipratropium has not been studied in patients with hepatic or renal insufficiency. Therapy with this agent should be used with caution in these patients.
Seizures
Moderate:
Combivent
The albuterol in Combivent has a moderate potential interaction with Seizures.
Adrenergic bronchodilators may cause CNS stimulation. Therapy with adrenergic bronchodilators should be administered cautiously in patients with seizure disorders. Systemic adverse effects are minimized, but not abolished, by administration of these agents via oral inhalation.
Moderate:
milnacipran
Milnacipran has a moderate potential interaction with Seizures.
SNRI antidepressants may trigger seizures and should be administered with caution in patients with a seizure disorder.
Urinary Retention
Moderate:
Combivent
The ipratropium in Combivent has a moderate potential interaction with Urinary Retention.
Aclidinium, ipratropium, umeclidinium, and tiotropium are anticholinergic agents. Although systemic effects are uncommon due to the poor absorption of quaternary ammonium compounds from gastrointestinal and nasal mucosa, worsening of urinary retention or angle-closure glaucoma has been reported. Increased intraocular pressure and precipitation or exacerbation of angle-closure glaucoma may also occur due to inadvertent contact of the eye with aerosolized or nebulized drug. Accordingly, therapy with quaternary ammonium compounds should be administered cautiously in patients with urinary retention/obstruction or angle-closure glaucoma. Measures should be taken whenever possible to minimize ocular exposure to these drugs, such as keeping eyes closed during oral inhalation or use of a mouthpiece rather than face mask during nebulization. Patients should be advised to contact their physician if they experience urinary difficulty (especially in patients with prostatic hyperplasia or bladder neck obstruction); or signs and symptoms of angle-closure glaucoma (e.g., eye pain or discomfort; blurred vision; visual halos; colored images in association with red eyes from conjunctival congestion or corneal edema).
Urinary Tract Infection
Moderate:
milnacipran
Milnacipran has a moderate potential interaction with Urinary Tract Infection.
SNRI antidepressants have a noradrenergic effect and can affect urethral resistance. Caution should be used in patients with a history of dysuria, prostatic hypertrophy, prostatitis, and other lower urinary tract obstructive disorders.
Urinary Tract Obstruction
Moderate:
milnacipran
Milnacipran has a moderate potential interaction with Urinary Tract Obstruction.
SNRI antidepressants have a noradrenergic effect and can affect urethral resistance. Caution should be used in patients with a history of dysuria, prostatic hypertrophy, prostatitis, and other lower urinary tract obstructive disorders.
More resources
Combivent
A total of 527 drugs are known to interact with Combivent.
- Combivent is in the drug class bronchodilator combinations.
- Combivent is used to treat COPD, Maintenance.
milnacipran
A total of 395 drugs are known to interact with milnacipran.
- Milnacipran is in the drug class serotonin-norepinephrine reuptake inhibitors.
-
Milnacipran is used to treat the following conditions:
- Fibromyalgia
- Reflex Sympathetic Dystrophy Syndrome (off-label)
- Somatoform Pain Disorder (off-label)
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
| No interaction information available. |
Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.