Generic Name: ipratropium
Brand Names: Atrovent, Atrovent HFA, Atrovent Nasal Spray
Drug Class: Anticholinergics, Respiratory; allergy, Intranasal
What is ipratropium, and what is it used for?
Ipratropium is a medication used to relieve runny nose and nasal inflammation (rhinitis) caused by colds and allergies, and as a bronchodilator to relieve bronchospasm and ease breathing in chronic obstructive pulmonary diseases (COPD), including chronic bronchitis and emphysema.
Ipratropium oral inhalations are used as maintenance treatment for COPD, while nasal sprays are used to relieve runny nose from allergic and nonallergic rhinitis.
Ipratropium is a respiratory anticholinergic medication that works by blocking the activity of acetylcholine in the respiratory tract. Acetylcholine is a chemical (neurotransmitter) that nerve cells release in neuromuscular junctions to make muscles contract. Acetylcholine also dilates blood vessels, increases secretion of body fluids, and slows heart rate. Acetylcholine works by stimulating molecules known as cholinergic receptors in various tissues.
Ipratropium nasal spray blocks the activity of acetylcholine on the cholinergic receptors in the nasal passage, reducing secretions by the serous and seromucous glands in the nasal mucous membrane. Ipratropium oral inhalation blocks acetylcholine activity in the bronchial smooth muscles, which relaxes the respiratory muscles and dilates the airway, making breathing easier.
Warnings
- Do not use ipratropium to treat patients with a history of hypersensitivity to atropine or its derivatives, ipratropium or any of the components in the formulation.
- If hypersensitive reactions occur, immediately discontinue ipratropium.
- Inhalation and nebulizers should be used only for maintenance treatment of COPD, not for initial treatment or acute bronchospasm episodes that require rescue therapy.
- Ipratropium can cause urinary retention, use with caution in patients with enlarged prostate (benign prostatic hyperplasia), bladder-neck obstruction or impaired kidney function.
- Inhaled bronchodilators including ipratropium may cause life-threatening paradoxical bronchospasm that should be differentiated from inadequate response.
- Use with caution in patients with narrow-angle glaucoma, a progressive disease with high intraocular pressure that damages the optic nerve. Ipratropium may further increase intraocular pressure.
- Use with caution in myasthenia gravis, a neuromuscular disease. Ipratropium may worsen symptoms.
- Ipratropium may cause dizziness, blurred vision, pupil dilation (mydriasis) and focusing difficulties (accommodation disorder). Advise patients appropriately.

QUESTION
Allergies can best be described as: See AnswerWhat are the side effects of ipratropium?
Common side effects of ipratropium include:
Intranasal
- Headache
- Upper respiratory tract infection (URI)
- Nasal bleeding (epistaxis)
- Throat inflammation (pharyngitis)
- Nasal dryness or irritation
- Nasal congestion
- Taste perversion
- Dry mouth (xerostomia)
- Increased thirst
- Nausea
- Diarrhea
Oral inhalation
- Bronchial inflammation (bronchitis)
- Exacerbation of COPD
- Sinus inflammation (sinusitis)
- Shortness of breath (dyspnea)
- Cough
- Flulike symptoms
- Back pain
- Headache
- Dizziness
- Urinary tract infection (UTI)
- Nausea
- Indigestion (dyspepsia)
- Dry mouth
Less common side effects of ipratropium include:
- Cough
- Dry and irritated throat
- Hoarseness
- Voice box spasm (laryngospasm)
- Burning sensation of the nose
- Nasal inflammation (rhinitis)
- Inflammation in the mouth (stomatitis)
- Blurred vision
- Inflammation of conjunctiva, the membrane over the eye whites and inner eyelid surfaces (conjunctivitis)
- Swelling of cornea (corneal edema)
- Eye irritation and red eye
- Eye focusing difficulty (accommodation disorder)
- Acute eye pain
- Increased intraocular pressure
- Glaucoma
- Dilation of pupils (mydriasis)
- Visual halos around lights
- Ringing in the ears (tinnitus)
- Low blood pressure (hypotension)
- Palpitations
- Rapid heart rate
- Reduced gastrointestinal motility
- Constipation
- Vomiting
- Urinary retention
- Skin rash
- Hives (urticaria)
- Itching (pruritus)
- Swelling in the tissue under the skin and mucous membranes (angioedema)
- Mouth edema
- Throat (pharyngeal) edema
- Severe allergic reaction (anaphylaxis)
This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug.
Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.
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What are the dosages of ipratropium?
- 17 mcg/actuation
Nebulized Solution
- 0.02%
Nasal Spray
- 0.03%
- 0.06%
Adult:
Chronic Obstructive Pulmonary Disease
- Maintenance treatment of bronchospasm, including chronic bronchitis and emphysema
- Inhaler: 2 actuations (34 mcg) every 6 hours, then additional actuations as needed; not to exceed 12 actuations/day (408 mcg/day)
- Nebulizer: 2.5 mL (500 mcg) every 6-8 hours
Acute Asthma Exacerbation (Off-label)
- Inhaler: 8 actuations (136 mcg) every 20 minutes as needed for 3 hours
- Nebulizer: 500 mcg every 20 minutes for 3 doses, then as needed
Administration
- Prime before initial use by releasing 2 test sprays into air; repeat priming if unused for 3 days or longer
Dosing Considerations
- In treatment of acute asthma exacerbation with inhaler, short-acting beta agonist (SABA) must be coadministered
Perennial Allergic/Nonallergic Rhinitis
- Nasal spray (0.03%): 2 sprays (21 mcg/spray) per nostril every 8-12 hours; not to exceed 168-252 mcg/day
- Seasonal allergic rhinitis: 2 sprays (0.06%) per nostril every 6 hours
Symptomatic relief of rhinorrhea (Common Cold)
- Nasal spray (0.06%): 2 sprays (0.42 mcg/spray) per nostril every 6 hours; not to exceed 672 mcg/day
Seasonal Allergic Rhinitis
- Nasal spray (0.06%): 2 sprays (0.42 mcg/spray) per nostril every 6 hours; not to exceed 672 mcg/day
Dosing Considerations
- In the treatment of allergic rhinitis, do not use for longer than 3 weeks
Pediatric:
Acute Asthma Exacerbation (Off-label)
NIH asthma guidelines
- Children younger than 5 years (inhaler): 2 inhalations every 20 minutes for 1 hour if necessary
- Children 5-12 years (inhaler): 4-8 actuations every 20 minutes as needed for up to 3 hours
- Children 12 years or older (inhaler): 8 actuations every 20 minutes as needed for up to 3 hours
- Children younger than 5 years (nebulizer): 0.25 mg (250 mcg) every 20 minutes for 1 hour if necessary
- Children 5-12 years (nebulizer): 250-500 mcg every 20 minutes for 3 doses, then as needed
- Children 12 years or older (nebulizer): 500 mcg every 20 minutes for 3 doses, then as needed
Symptomatic Relief of Rhinorrhea (Colds)
- Children younger than 5 years: Safety and efficacy not established
- Children 5-12 years: 2 sprays (0.06%) in each nostril every 8 hours
- Children older than 12 years: 2 sprays (0.06%) in each nostril every 6-8 hours
Allergic/Nonallergic Rhinitis
- Children younger than 6 years: Safety and efficacy not established
- Children older than 6 years: 2 sprays (0.03%) per nostril every 8-12 hours
Seasonal Allergic Rhinitis
- Children younger than 5 years: Safety and efficacy not established
- Children older than 5 years: 2 sprays (0.06%) per nostril every 6 hours
Overdose
- Overdosage of ipratropium nasal spray or oral inhalation is unlikely because it is not systemically well absorbed.
What drugs interact with ipratropium?
Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.
Ipratropium has no known severe interactions with other drugs.
- Serious interactions of ipratropium include:
- glucagon
- glucagon intranasal
- macimorelin
- pramlintide
- revefenacin
- umeclidinium bromide/vilanterol inhaled
- Ipratropium has moderate interactions with at least 94 different drugs.
- Mild interactions of ipratropium include:
- dimenhydrinate
- donepezil
- galantamine
- levodopa
The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.
It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.
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Pregnancy and breastfeeding
- Ipratropium use may be acceptable during pregnancy because ipratropium oral inhalation and nasal spray are poorly absorbed systemically. There are no adequate and well-controlled studies of ipratropium use during pregnancy, however, animal reproductive studies revealed no evidence of fetal risk.
- It is not known if ipratropium is excreted in breast milk, however, because many drugs are excreted in breast milk, use with caution in nursing mothers.
What else should I know about ipratropium?
- Use ipratropium exactly as directed.
- Ipratropium is only for maintenance treatment in COPD. Seek medical help if you have an acute episode of bronchospasm.
- Do not use ipratropium nasal spray for longer than four days for your cold or three weeks for seasonal allergic rhinitis unless instructed by your physician.
- Avoid contact with eyes. In case of accidental contact, wash the eye with plenty of cool water for several minutes. If eye pain or blurry vision persists after a few hours, consult with your physician.
- Ipratropium may cause dizziness and blurry vision. Avoid hazardous tasks such as driving and operating heavy machinery.
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Summary
Ipratropium is a medication used to relieve runny nose and nasal inflammation (rhinitis) caused by colds and allergies, and as a bronchodilator to relieve bronchospasm and ease breathing in chronic obstructive pulmonary diseases (COPD), including chronic bronchitis and emphysema. Common side effects of intranasal ipratropium include headache, upper respiratory tract infection (URI), nasal bleeding (epistaxis), throat inflammation (pharyngitis), and others. Common side effects of intranasal ipratropium include bronchial inflammation (bronchitis), exacerbation of COPD, sinus inflammation (sinusitis), shortness of breath (dyspnea), cough, flulike symptoms, back pain, and others.
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How to Get Rid of a Sinus Infection
A sinus infection, also known as sinusitis or rhinosinusitis, is a condition where the nasal passages become swollen and infected. The sinuses are hollow air spaces in the facial bones, near the nose. They produce mucus, which helps line the nose and prevent dust and other particles from entering the lungs.
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What Nuts Are the Worst for Allergies?
A nut allergy develops when the body's immune system becomes oversensitive to a particular protein in a nut. Nuts that are the worst for allergies include peanuts, walnuts, pecans, almonds, Brazil nuts and pine nuts.
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How Can You Tell if You Have a Sinus Infection?
Sinus infection is a common issue that affects many people. Learn the signs of sinus infection, what causes sinus infection, how doctors diagnose sinus infection, and what you can do to treat sinus infection.
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Sinus Infection vs. Cold
Viruses cause the common cold and most sinus infections. Bacterial and fungal infections may also cause a sinus infection. Signs and symptoms of colds and sinus infections include nasal irritation or dryness, sore throat, stuffy nose, nasal discharge/congestion, sneezing, and cough. Additional symptoms of sinus infections include sinus pressure behind the cheeks or eyes, facial pain when pressure is applied, bad breath, and thick yellow or green mucus. Treatment focuses on symptom relief.
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Insect Sting Allergies
The majority of stinging insects in the United States are from bees, yellow jackets, hornets, wasps, and fire ants. Severity of reactions to stings varies greatly. Avoidance and prompt treatment are essential. In selected cases, allergy injection therapy is highly effective.
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Sinus Infection vs. Allergies
Both sinus infections and allergies (allergic rhinitis) cause symptoms such as runny or stuffy nose and fatigue. Sinus infection (known as sinusitis) is inflammation of the sinuses, caused by infection from bacteria, viruses, and/or fungi (molds). Allergic rhinitis occurs when certain allergies cause nasal symptoms. When a person with allergies breathes in an allergen, such as pollen, dust, or animal dander, symptoms such as runny or stuffy nose, itching, sneezing, and fatigue occur.
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Are Food Allergies Passed Down Genetically?
A food allergy is a condition that causes your immune system to fight against a particular part of food — which is called an allergen. Food allergies can be hereditary — that is, parents can pass the likelihood of developing a food allergy to their children through genes that code for inherited traits.
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How Do You Know if You Have a Sinus Infection (Sinusitis) or COVID-19 Coronavirus?
Learn how the signs and symptoms of a sinus infection are different from those caused by COVID-19.
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Can Hot Weather Cause Sinus Problems?
Sinusitis is a condition where you experience irritation and swelling of your sinuses. Allergies and sinus problems are common during the warmer seasons.
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Is It a Cold or a Sinus Infection?
A sinus infection, also known as sinusitis or rhinosinusitis, is a condition in which the delicate membranes that line the sinuses may get swollen and become red. A cold or common cold is a viral infection. It affects the upper respiratory system, which includes the nose, mouth, throat, and lungs.
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How to Get Rid of a Sinus Infection Fast
The sinuses are air-filled cavities that surround the nose and drain into the nose. They are present in the forehead, the cheeks and near the eyes. Treatment for sinus infections includes over-the-counter pain relievers, decongestants, antibiotics, humidifiers, nasal irrigation, steam inhalation, rest, hydration and warm compresses.
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How Do You Use Nasal Packing for Epistaxis?
Nasal packing may be “anterior” nasal packing that is done by using a gauze inserted inside the nasal cavity after numbing the nasal area. The doctor will douse the gauze in an antibiotic ointment and a medication that squeezes the blood vessels shut.
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Drug Allergy (Medication Allergy)
Drug or medication allergies are caused when the immune system mistakenly creates an immune response to a medication. Symptoms of a drug allergic reaction include hives, rash, itchy skin or eyes, dizziness, nausea, diarrhea, fainting, and anxiety. The most common drugs that people are allergic to include penicillins and penicillin type drugs, sulfa drugs, insulin, and iodine. Treatment may involve antihistamines or corticosteroids. An EpiPen may be used for life-threatening anaphylactic symptoms.
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COVID-19 vs. Allergies
Though there is some overlap in allergy and COVID-19 signs and symptoms there are also significant differences. Symptoms that they have in common include headache, fatigue, tiredness, shortness of breath, wheezing, and sore throat. Fever does not occur with allergies but is one of the defining symptoms of COVID-19 infections.
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How Long Does Sinusitis Last?
Sinuses are air-filled cavities in the skull that surround the nose. They are present in the forehead, cheeks, and near the eyes. These are closed spaces in the skull with a small opening.
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What Is the Fastest Way to Get Rid of a Sinus Infection?
Learn what medical treatments can help ease your sinus infection symptoms and speed up your recovery.
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How Are Nasal Polyps Removed?
The surgical removal of nasal polyps is known as nasal polypectomy. The procedure is mainly performed under local anesthesia or general anesthesia. The physician relieves congestion of the nose using oxymetazoline drops or pellets. The polyps are removed with the help of polyp forceps without injuring the surrounding tissue.
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Is a Nasal Endoscopy Painful?
Nasal endoscopy or rhinoscopy is not a painful procedure; however, it may be slightly uncomfortable. Before nasal endoscopy, the doctor may spray the nose with a decongestant and local anesthesia to reduce the congestion and widen the area while stopping the patient from sneezing or discomfort.
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What Can You Take for a Cold While Pregnant?
You may take over-the-counter (OTC) treatment after consulting with the physician because these are generally safe. OTC medications for colds and flus include acetaminophen, guaifenesin syrup and saline nasal drops or spray. You can also use natural remedies to treat a cold during pregnancy.
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How Can Teens Cope With A Cold?
Usually, teens have a healthy immune system to cope with common cold. Getting plenty of rest and drinking lots of fluids can ease the symptoms.
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Emphysema, Chronic Bronchitis, and Colds
If you have a COPD such as emphysema, avoiding chronic bronchitis and colds is important to avoid a more severe respiratory infection such as pneumonia. Avoiding cigarette smoking, practice good hygeine, stay away from crowds, and alerting your healthcare provider if you have a sinus infection or cold or cough that becomes worse. Treatment options depend upon the severity of the emphysema, bronchitis, or cold combination.
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What Are the 5 Main Symptoms of Sinusitis?
Common symptoms of sinusitis include runny or stuffy nose, postnasal drip, headache, facial pain and swelling, and reduced sense of smell or taste.
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What Is Petrosal Sinus Sampling?
Although the procedure is not painful, you may experience minor pain when the catheter (tubing) is passed through the veins. You may also experience pain at the puncture site.
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What Is the Fastest Way to Fix Seasonal Allergies?
Seasonal allergies are common and tend to ramp up during the spring and summer. Learn about how to get rid of seasonal allergies fast with these 13 home remedies.
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What Are Postnasal Drip Medications?
Postnasal drips refer to the feeling of mucus collecting or dripping inside the throat from the back of your nose (postnasally). This may occur when there is excess mucus formation, when the mucus becomes too thick or when the normal flow of mucus is blocked or hindered.
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What Can Trigger a Cold Sore?
After you get infected with HSV, it lies inactively in the nerve cells inside your skin and may appear as another cold sore at the same place as before.
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What Causes Chronic Sinusitis?
Chronic sinusitis occurs when the tissue lining the facial sinuses becomes inflamed for at least three months. Chronic sinusitis usually involves nasal airway swelling (rhinitis). The causes of chronic sinusitis include nasal polyps, deviated nasal septum, medical conditions, respiratory tract infections, and allergies.
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What Causes Nose Allergies?
Nose allergies can be caused by irritants such as pollen, animal dander, and household dust. Learn about symptoms, treatment, and prevention.
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How Long Does a Cold Last?
Most often, a common cold lasts anywhere from 5 to 10 days in length.
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What Is Posterior Nasal Packing?
Posterior nasal packing is a procedure to control the bleeding from the behind (posterior aspect) of the nose. Posterior bleeding is much less common than anterior bleeding and usually is treated by the ear, nose, and throat surgeon (an otolaryngologist). Posterior nosebleeds involve bleeding from the back of the nasal cavity.
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What Medication Is Best for Sinusitis?
Sinusitis occurs when the tissues lining the sinus cavities become swollen as a result of an infection or irritation. Medications for sinusitis vary depending on the severity of the condition.
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Functional Endoscopic Sinus Surgery
Functional endoscopic sinus surgery (FESS) is a minimally invasive sinus surgery performed using a rigid endoscope (a tool with camera at one end). The primary objective of FESS is to restore ventilation of the sinuses and facilitate the clearing of nasal secretions.
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What Do You Give a Child With a Cold?
Unfortunately, there is no cure for the common cold. Antibiotics may be used to fight bacterial infections, but they have no effect on viruses.
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When to See a Doctor When Your Baby Has a Cold
If your baby has a cold, signs that it may be time to see a doctor include poor feeding, dehydration, breathing difficulties, ear pain, and more.
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What Is Good for a Child's Cold?
The common cold is one of the main reasons for missing schools in children and missing work in adults. Children are affected more commonly with cold than adults, who may have an average of two to three colds each year.
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Should I Exercise Outside if I Have Allergies?
An allergy is a condition in which the immune system overresponds to a foreign substance. With the right treatment and precautions, you can completely eliminate allergy flare-ups during your outdoor workout.
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What Helps Sinus Congestion and Pain?
Sinus congestion and pain can be relieved at home by keeping your nasal passages moist and taking over-the-counter medications that help reduce inflammation.
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Why Are Allergies So Bad Right Now 2021?
Scientists believe that allergies are getting worse because of climate change.
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How Do You Tell If Your Child Has Allergies or a Cold?
Colds and allergies have different causes, but both involve the body's immune system. Since the symptoms of allergies and the symptoms of a cold overlap, it can be hard to tell which one your child has.
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How Do You Get Tested for Food Allergies?
If you develop symptoms of a food allergy, your doctor will have you undergo a skin test or blood test to determine which foods you are allergic to.
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When should a nasal fracture be reduced?
Nasal endoscopy or rhinoscopy is not a painful procedure; however, it may be slightly uncomfortable. Before nasal endoscopy, the doctor may spray the nose with a decongestant and local anesthesia to reduce the congestion and widen the area while stopping the patient from sneezing or discomfort.
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Is My Sore Throat Allergies or COVID-19?
Sore throat can be a symptom of allergies or COVID-19, and it can be difficult to tell which one you have. Understanding the difference between these two illnesses can help.
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How Do You Get a Cold Sore on Your Lip?
Cold sores, also called fever blisters or oral herpes, are a viral infection that leaves small blisters around your mouth. You get a cold sore on your lip due to viral infection from herpes simplex virus type 1 (HSV-1).
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Can Fall Allergies Cause Sinus Headaches?
Fall allergies can cause symptoms such as sneezing, congestion, and sinus headache. Learn more about causes, treatment, and prevention of fall allergies.
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How to Identify Cold Symptoms in Children
When a child is sick, their way of showing it may not always be clear. Here’s what to look for to determine whether your child is sick with a cold.
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How Do You Treat a Cold Naturally?
Hundreds of viruses and bacteria can cause the common cold and flu. Most cases of cold and flu usually resolve in a week with simple home remedies and over the counter (OTC) medications. If there is no improvement in a few days, it is advised to consult a doctor.
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How Is COVID-19 Different From Allergies?
COVID-19 symptoms are often similar to symptoms of seasonal allergies, so it is important to know how to tell the difference. Learn how to distinguish between the two.
Treatment & Diagnosis
- Nasal Congestion
- Postnasal Drip
- Sinus Infection (Sinusitis)
- Allergy
- Food Allergy
- Latex Allergy
- Acute Sinusitis
- Makeup Allergy
- Allergy Attacks? Fight Back
- Allergies- Easing Sneezing: House Cleaning Tips
- Eye Allergy
- Sinus Headache
- Drug Allergy
- Peanut Allergy
- Insect Sting Allergy
- Allergy: Winning the War Against Allergies
- Allergy: Taking the Sting Out of Insect Allergies
- Peanut and Other Food Allergies -- Scott Sicherer, MD
- Asthma and Allergies and Your Child
- Allergies: Mold and More:Battling Indoor Allergens
- Allergies, Control Your Spring
- Allergies FAQs
- Cold & Flu FAQs
- Common Cold FAQs
- Food Allergies vs. Food Intolerance
- Colds: 10 Tips to Prevent The Common Cold
- Killer Cold Virus (Adenovirus Strains)
- Common Cold . . . Social Ties Decrease Risk
- Colds: Zinc For Colds...Jury Still Out!
- Cough, Cold, Weight Loss Drug Dangerous - Warning
- Air Pollution and Allergies: A Connection?
- Nasal Flu Vaccine for Children
- Allergies: Don't Sneeze at Allergy Relief
- What Are Strategies to Deal With Mite Allergies ?
- Do Anti-Mite Carpet Cleaners Help Mite Allergies?
- What Kind of Cold Medicine Can Diabetics Take?
- Cold Sore Treatment
- OTC Cold and Cough Medications
- When to Call the Doctor for Fever, Nausea, Diarrhea, Colds, and Coughs
- Air Travel, Colds, and Sinus Infections
Medications & Supplements
- fluticasone (Flonase, Flonase Allergy Relief)
- Nasal Decongestants
- sodium chloride - intranasal spray (Ocean, Ayr Saline, Humist, NaSal, Little Noses, Ocean)
- decongestant spray - nasal
- Zinc for Colds: Lozenges & Nasal Sprays
- fluticasone furoate nasal spray (Veramyst)
- Side Effects of Flonase (fluticasone)
- Cold Medicine and Cough Syrup for Adults
- triamcinolone acetonide nasal inhaler (Nasacort)
- budesonide nasal inhaler (Rhinocort Allergy, Rhinocort Aqua)
- decongestant drops - nasal
- Side Effects of Nasalcrom (cromolyn sodium)
- Nasal Allergy Medications
- flunisolide nasal spray, Aerospan (Nasalide, Aerobid, Aerobid HFA are discontinued)
- Side Effects of Rhinocort Aqua (budesonide)
- beclomethasone dipropionate nasal inhaler-spray
- Side Effects of FluMist (influenza nasal vaccine live)
- FluMist, FluMist Quadrivalent influenza vaccine live intranasal
- beclomethasone - nasal, Beconase Aq, Vancenase Aq
- desmopressin solution - nasal, DDAVP
- Lazanda (fentanyl) nasal spray
Prevention & Wellness
Health Solutions From Our Sponsors

Report Problems to the Food and Drug Administration
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https://reference.medscape.com/drug/atrovent-atrovent-hfa-ipratropium-343416#0
https://reference.medscape.com/drug/atrovent-nasal-spray-ipratropium-999639#0
https://www.uptodate.com/contents/ipratropium-oral-inhalation-drug-information#F8120045
https://www.uptodate.com/contents/ipratropium-nasal-drug-information#F8119882
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021527s021lbl.pdf
https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/020394s005lbl.pdf
https://www.ncbi.nlm.nih.gov/books/NBK544261/