Entre-S

• Acella Pharmaceuticals, LLC

• Brookstone Pharmaceuticals, Inc.

Do not use this medicine if you have taken an MAO inhibitor in the past 14 days. A dangerous drug interaction could occur. MAO inhibitors include isocarboxazid, linezolid, phenelzine, rasagiline, selegiline, and tranylcypromine.

Do not use chlorpheniramine, dextromethorphan, and pseudoephedrine if you have taken an MAO inhibitor in the past 14 days. A dangerous drug interaction could occur. MAO inhibitors include isocarboxazid, linezolid, phenelzine, rasagiline, selegiline, and tranylcypromine.

To make sure this medicine is safe for you, tell your doctor if you have:

• asthma or COPD, cough with mucus, or cough caused by smoking, emphysema, or chronic bronchitis;

• a blockage in your digestive tract (stomach or intestines);

• high blood pressure, heart disease;

• liver or kidney disease;

• glaucoma;

• cough with mucus, or cough caused by emphysema or chronic bronchitis;

• enlarged prostate or urination problems;

• pheochromocytoma (an adrenal gland tumor);

• overactive thyroid; or

• if you take potassium (Cytra, Epiklor, K-Lyte, K-Phos, Kaon, Klor-Con, Polycitra, Urocit-K).

FDA pregnancy category C. It is not known whether chlorpheniramine, dextromethorphan, and pseudoephedrine will harm an unborn baby. Do not use this medicine without a doctor's advice if you are pregnant.

This medicine can pass into breast milk and may harm a nursing baby. Antihistamines and decongestants may also slow breast milk production. Do not use this medicine without a doctor's advice if you are breast-feeding a baby.

Use exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Cough or cold medicine is usually taken only for a short time until your symptoms clear up.

Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children.

Measure liquid medicine with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.

The chewable tablet must be chewed before you swallow it.

Do not take for longer than 7 days in a row. Talk with your doctor if your symptoms do not improve after 7 days of treatment, or if you have a fever with a headache or skin rash.

If you need surgery or medical tests, tell the surgeon or doctor ahead of time if you have taken this medicine within the past few days.

Store at room temperature away from moisture and heat.

Drinking alcohol can increase certain side effects of chlorpheniramine, dextromethorphan, and pseudoephedrine.

Ask a doctor or pharmacist before using any other cold, cough, allergy, or sleep medicine. Antihistamines and cough suppressants are contained in many combination medicines. Taking certain products together can cause you to get too much of a certain drug. Check the label to see if a medicine contains an antihistamine or cough suppressant.

This medication may cause blurred vision and may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert and able to see clearly.

Avoid becoming overheated or dehydrated during exercise and in hot weather. Chlorpheniramine and pseudoephedrine can decrease sweating and you may be more prone to heat stroke.

Dextromethorphan is an antitussive agent which, unlike the isomeric levorphanol, has no analgesic or addictive properties. The drug acts centrally and elevates the threshold for coughing. It is about equal to codeine in depressing the cough reflex. In therapeutic dosage, dextromethorphan does not inhibit ciliary activity. Dextromethorphan is rapidly absorbed from the gastrointestinal tract, metabolized by the liver and excreted primarily in the urine.

Pseudoephedrine is an α-adrenergic receptor antagonist (sympathomimetic) which produces vasoconstriction by stimulating α-receptors within the mucosa of the respiratory tract. Clinically, pseudoephedrine shrinks swollen mucous membranes, reduces tissue hyperemia, edema, and nasal congestion, and increases nasal airway patency. The vasoconstriction action of pseudoephedrine is similar to that of ephedrine. In the usual dose it has minimal vasopressor effects. Pseudoephedrine is rapidly and almost completely absorbed from the gastrointestinal tract. Acidic urine is associated with faster elimination of the drug. The drug is distributed to body tissues and fluids, including the fetal tissue, breast milk and the central nervous system (CNS).

Chlorpheniramine is an alkylamine-type antihistamine. The antihistamine in Entre-S Suspension acts by competing with histamine for H1 histamine receptor sites, thereby preventing the action of histamine on the cell. Clinically, chlorpheniramine suppresses the histamine-mediated symptoms of allergic rhinitis, relieving sneezing, rhinorrhea, and itching of the eyes, nose, and throat.

Entre-S Suspension is contraindicated in patients with hypersensitivity to chlorpheniramine, dextromethorphan, or with hypersensitivity or idiosyncrasy to sympathomimetic amines which may be manifested by insomnia, dizziness, weakness, tremor or arrhythmias. Sympathomimetic amines are contraindicated in patients with severe hypertension, severe coronary artery disease, and patients that are now taking a prescription monoamine oxidase inhibitor (MAOI) (certain drugs for depression, psychiatric, or emotional conditions, or Parkinson's disease), or for two weeks after stopping the MAOI drug. This product is contraindicated in women who are pregnant or nursing.

Applies to chlorpheniramine / dextromethorphan / pseudoephedrine: oral liquid, oral suspension extended release, oral tablet chewable

Nervous system

Nearly all patients treated with chlorpheniramine experience drowsiness. This drowsiness may subside in some patients with extended use.

Few cases of dyskinesias and tremors, often of the face, have been reported in patients whose chronic use of chlorpheniramine extended over a period of 3 to 10 years. Some of these cases were only partially relieved by discontinuation of the drug. Haloperidol was successful in relieving symptoms.[Ref]

Nervous system side effects of chlorpheniramine have included drowsiness in 75% or more of treated patients. Dyskinesias have rarely been reported following chronic use of chlorpheniramine.

Nervous system side effects of dextromethorphan have included drowsiness and dizziness. Other side effects such as excitation, mental confusion, and opioid like respiratory depression have been rare and occurred at higher dosages. In some cases of abuse, patients experienced euphoria, hyperactivity, mania, and auditory and visual hallucinations.

Nervous system side effects of pseudoephedrine have included insomnia in up to 30% of patients. Tremor, anxiety, nervousness, and headache have also been reported.[Ref]

Gastrointestinal

Gastrointestinal side effects of chlorpheniramine have included dry mouth and constipation in up to one-third of treated patients.

Gastrointestinal side effects of dextromethorphan have included stomach upset.

Gastrointestinal side effects of pseudoephedrine have included anorexia and gastric irritation in approximately 5% of patients. Dry mouth, nose, or throat have occurred in up to 15% of patients.[Ref]

Cardiovascular

Pseudoephedrine causes vasoconstriction which generally does not produce hypertension, but may be problematic for patients with preexisting hypertension. Arrhythmias may be produced in predisposed patients. Rarely, pseudoephedrine has been reported to cause coronary artery spasm and chest pain.

One report evaluated the effect with 60 mg of pseudoephedrine on individuals in a hyperbaric chamber at 1 atmosphere (simulated scuba dive to 66 feet of sea water). Pseudoephedrine and depth (simulated) were found to have significant but opposite effects on heart rate, although these effects were unlikely to be clinically significant during diving.[Ref]

Cardiovascular side effects of chlorpheniramine have included hypotension, tachycardia, and palpitations.

Cardiovascular side effects of pseudoephedrine have included tachycardia. Some patients have developed hypertension and/or arrhythmias.[Ref]

Ocular

Ocular effects of chlorpheniramine have included blurred vision, diplopia, and dry eyes due to anticholinergic effects.[Ref]

Genitourinary

Genitourinary side effects of chlorpheniramine have included dysuria, urinary hesitancy, and a decreased urine flow. In rare cases, the anticholinergic effect of chlorpheniramine has precipitated acute urinary retention.[Ref]

Hematologic

Hematologic side effects of chlorpheniramine have included bone marrow suppression, thrombocytopenia, and aplastic anemia.[Ref]

A fatal case of agranulocytosis has been reported in a patient taking chlorpheniramine, pseudoephedrine, acetaminophen, dextromethorphan, phenylpropanolamine, and aspirin. Chlorpheniramine was felt to be the cause.[Ref]

Hypersensitivity

Hypersensitivity side effects of dextromethorphan have included rare reports of fixed-drug eruptions.

Hypersensitivity side effects of pseudoephedrine have included fixed-drug eruptions.[Ref]

Some side effects of Entre-S may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.