RYNATAN® Long-Acting Antihistamine/Decongestant Tablets contain 1 mg azatadine maleate, USP in the tablet coating and 120 mg pseudoephedrine sulfate, USP, equally distributed between the tablet coating and the barrier-coated core. Following ingestion, the two active components in the coating are quickly liberated; release of the decongestant in the core is delayed for several hours.

Azatadine maleate is an antihistamine having the empirical formula, C 20 H 22 N 2 ·2C 4 H 4 O 4 , the chemical name, 6,11-Dihydro-11-(-methyl-4-piperidylidene)-5 H -benzo [5,6] cyclohepta [1,2- b ] pyridine maleate (1:2), and the chemical structure:


The molecular weight of azatadine maleate is 522.54. Azatadine maleate is a white to off-white powder and is very soluble in water and soluble in alcohol.

Pseudoephedrine sulfate, a sympathomimetic amine, is a salt of pseudoephedrine, one of the naturally occurring alkaloids obtained from various species of the plant Ephedra . The empirical formula for pseudoephedrine sulfate is (C 10 H 15 NO) 2 ·H 2 SO 4 ; the chemical name is Benzenemethanol, (alpha)-[1-(methylamino)ethyl]-, [S-(R*,R*)]-, sulfate (2:1) (salt), and the chemical structure is:


The molecular weight of pseudoephedrine sulfate is 428.56. It is a white to off-white crystal or powder, very soluble in water, freely soluble in alcohol, and sparingly soluble in chloroform.

The inactive ingredients for RYNATAN® Tablets are: acacia, butylparaben, calcium sulfate, carnauba wax, corn starch, D&C Red No. 30 Al Lake, FD&C Yellow No. 6 Al Lake, gelatin, lactose, magnesium stearate, neutral soap, oleic acid, povidone, rosin, sugar, talc, white wax, and zein.

Azatadine maleate is an antihistamine, related to cyproheptadine, with antiserotonin, anticholinergic (drying), and sedative effects. Antihistamines appear to compete with histamine for histamine H 1 -receptor sites on effector cells. The antihistamines antagonize those pharmacological effects of histamine which are mediated through activation of H 1 -receptor sites and thereby reduce the intensity of allergic reactions and tissue injury response involving histamine release. Antihistamines antagonize the vasodilator effect of endogenously released histamine, especially in small vessels, and mitigate the effect of histamine which results in increased capillary permeability and edema formation. As consequences of these actions, antihistamines antagonize the physiological manifestations of histamine release in the nose following antigen-antibody interaction, such as congestion related to vascular engorgement, mucosal edema, and profuse, watery secretion, and irritation and sneezing resulting from histamine action of afferent nerve terminals.

Pseudoephedrine sulfate (d-isoephedrine sulfate) is an orally effective nasal decongestant which appears to exert its sympathomimetic effect indirectly, predominantly through release of adrenergic mediators from postganglionic nerve terminals. In effective recommended oral dosage, pseudoephedrine sulfate produces minimal other sympathomimetic effects, such as pressor activity and CNS stimulation. Use of an orally administered vasoconstrictor for shrinkage of congested nasal mucosa has several advantages: a) it produces a gradual but sustained decongestant effect, causing little, if any "rebound" congestion; b) it facilitates shrinkage of swollen mucosa in upper respiratory areas that are relatively inaccessible to topically applied sprays or drops; c) it relieves nasal obstruction without the additional irritation that may result from local medication.

Pseudoephedrine passes through the blood-brain and placental barriers. While the antihistamines have not been studied systematically for passage through these barriers, the occurrence of pharmacologic effects in the central nervous system and in newborns indicate presence of the drug.

Following administration of the two drugs to normal volunteers in either a single RYNATAN® Tablet or similar doses in two conventional pseudoephedrine sulfate tablets and a conventional tablet of azatadine maleate, the blood levels of pseudoephedrine and the urinary excretion of azatadine showed that the RYNATAN® Tablets are bioequivalent to the conventional dosage forms. The apparent elimination half-life of pseudoephedrine in RYNATAN® Tablets was approximately 6 ½ hours. The apparent elimination half-life of azatadine maleate (available from the outer layer of the RYNATAN® Tablets or from the conventional azatadine maleate tablet) was approximately 12 hours.

RYNATAN® Long-Acting Antihistamine/Decongestant Tablets are indicated for the relief of the symptoms of upper respiratory mucosal congestion in perennial and allergic rhinitis, and for the relief of nasal congestion and eustachian tube congestion. Analgesics, antibiotics, or both may be administered concurrently, when indicated.


Antihistamines should not be used to treat lower respiratory tract symptoms, including asthma.

This product is contraindicated in patients with narrow-angle glaucoma or urinary retention, and in patients receiving monoamine oxidase (MAO) inhibitor therapy or within 2 weeks of stopping such treatment. (See Drug Interactions section.) It is also contraindicated in patients with severe hypertension, severe coronary artery disease, hyper-thyroidism, and in those who have shown hypersensitivity or idiosyncrasy to its components, to adrenergic agents, or to other drugs of similar chemical structures. Manifestations of patient idiosyncrasy to adrenergic agents include: insomnia, dizziness, weakness, tremor, or arrhythmias.

RYNATAN® Tablets should be used with considerable caution in patients with: stenosing peptic ulcer, pyloroduodenal obstruction, urinary bladder obstruction due to symptomatic prostatic hypertrophy, or narrowing of the bladder neck. It should also be administered with caution to patients with: cardiovascular disease, including hypertension or ischemic heart disease; increased intraocular pressure (see CONTRAINDICATIONS ); diabetes mellitus; or in patients receiving digitalis or oral anticoagulants.

Central nervous system stimulation and convulsions or cardiovascular collapse with accompanying hypotension may be produced by sympathomimetics.

Do not exceed recommended dosage.

Use in Activities Requiring Mental Alertness: Patients should be warned about engaging in activities requiring mental alertness, such as driving a car or operating appliances, machinery, etc.

Use in Patients Approximately 60 Years and Older: Antihistamines are more likely to cause dizziness, sedation, and hypotension in patients over 60 years of age. In these patients, sympathomimetics are also more likely to cause adverse reactions, such as confusion, hallucinations, convulsions, CNS depression and death. For this reason, before considering the use of a repeat-action formulation, the safe use of a short-acting sympathomimetic in that particular patient should be demonstrated.


General:   Because of the atropine-like action of antihistamines, this product should be used with caution in patients with a history of bronchial asthma.

Information for Patients:

  1. Products containing antihistamines may cause drowsiness.
  2. Patients should not engage in activities requiring mental alertness, such as driving or operating machinery or appliances.
  3. Alcohol or other sedative drugs may enhance the drowsiness caused by antihistamines.
  4. Patients should not take RYNATAN® Tablets if they are receiving a monoamine oxidase inhibitor or within 2 weeks of stopping such treatment, or if they are receiving oral anticoagulants.
  5. This medication should not be given to children less than 12 years of age.

Drug Interactions:   MAO inhibitors prolong and intensify the effects of antihistamines. Concomitant use of antihistamines with alcohol, tricyclic antidepressants, barbiturates, or other central nervous system depressants may have an additive effect.

When sympathomimetic drugs are given to patients receiving monoamine oxidase inhibitors, hypertensive reactions, including hypertensive crises, may occur. The antihypertensive effects of methyldopa, mecamylamine, reserpine, and veratrum alkaloids may be reduced by sympathomimetics. Beta-adrenergic blocking agents may also interact with sympathomimetics. Increased ectopic pacemaker activity can occur when pseudoephedrine is used concomitantly with digitalis. Antacids increase the rate of absorption of pseudoephedrine, while kaolin decreases it.

Drug/Laboratory Test Interactions:   The in vitro addition of pseudoephedrine to sera containing the cardiac isoenzyme MB of serum creatine phosphokinase progressively inhibits the activity of the enzyme. The inhibition becomes complete over 6 hours.

Carcinogenesis, Mutagenesis, and Impairment of Fertility:   There is no animal or laboratory study of the mixture of azatadine maleate and pseudoephedrine sulfate to evaluate carcinogenesis or mutagenesis. Reproduction studies of this mixture in rats showed no evidence of impaired fertility.

Pregnancy Category C:   Retarded fetal development and the presence of angulated hyoid wings were seen in the offspring of pregnant rabbits administered RYNATAN® Tablets at about 12.5 times and 5 times the recommended human dosage, respectively; increased resorption was noted at about 25 times the human dosage. A decreased survival rate at day 21 was seen in rat pups born of mothers given RYNATAN® Tablets during pregnancy at a dose about 12.5 times the human dosage. There are no adequate and well-controlled studies in pregnant women. RYNATAN® Tablets should be used during pregnancy only if the potential benefits to the mother justify the potential risks to the infant. (See Nonteratogenic Effects .)

Nonteratogenic Effects: Antihistamines should not be used in the third trimester of pregnancy because newborns and premature infants may have severe reactions to them, such as convulsions.

Nursing Mothers:   It is not known whether these drugs are excreted in human milk. However, certain antihistamines and sympathomimetics are known to be excreted in human milk. Because of the higher risks of antihistamines for infants generally and for newborns and prematures in particular, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

There is a report of irritability, excessive crying, and disturbed sleeping patterns in a nursing infant whose mother had taken a product containing an antihistamine and pseudoephedrine.

Pediatric Use:   Safety and effectiveness in children below the age of 12 years have not been established.


The following adverse reactions are associated with antihistamine and sympathomimetic drugs. (Those adverse reactions which occur most frequently with the antihistamines are underlined.)

General:   Urticaria, drug rash; anaphylactic shock; photosensitivity; excessive perspiration; chills; dryness of mouth, nose, and throat.

Cardiovascular:   Hypertension (see CONTRAINDICATIONS and ), hypotension, arrhythmias and cardiovascular collapse, headache, palpitations, extrasystoles, tachycardia, angina.

Hematologic:   Hemolytic anemia, hypoplastic anemia, thrombocytopenia, agranulocytosis.

Central Nervous System:    Sedation, sleepiness, dizziness , vertigo, tinnitus, acute labyrinthitis, disturbed coordination , fatigue, mydriasis, confusion, restlessness, excitation, nervousness, tension, tremor, irritability, insomnia, euphoria, paresthesias, blurred vision, hysteria, neuritis, convulsions, fear, anxiety, hallucinations, CNS depression, weakness, pallor.

Gastrointestinal:    Epigastric distress , anorexia, nausea, vomiting, diarrhea, constipation, abdominal cramps.

Genitourinary   Urinary frequency, urinary retention, dysuria, early menses.

Respiratory:    Thickening of bronchial secretions , tightness of chest and wheezing, nasal stuffiness, respiratory difficulty.


There is no information to indicate that abuse or dependency occurs with azatadine maleate.

Pseudoephedrine, like other central nervous system stimulants, has been abused. At high doses, subjects commonly experience an elevation of mood, a sense of increased energy and alertness, and decreased appetite. Some individuals become anxious, irritable, and loquacious. In addition to the marked euphoria, the user experiences a sense of markedly enhanced physical strength and mental capacity. With continued use, tolerance develops, the user increases the dose, and toxic signs and symptoms appear. Depression may follow rapid withdrawal.


In the event of overdosage, emergency treatment should be started immediately.

Manifestations of overdosage may vary from central nervous system depression (sedation, apnea, diminished mental alertness, cyanosis, coma, cardiovascular collapse) to stimulation (insomnia, hallucinations, tremors, or convulsions) to death. Other signs and symptoms may be euphoria, excitement, tachycardia, palpitations, thirst, perspiration, nausea, dizziness, tinnitus, ataxia, blurred vision, and hypertension or hypotension. Stimulation is particularly likely in children, as are atropine-like signs and symptoms (dry mouth; fixed, dilated pupils; flushing; hyperthermia; and gastrointestinal symptoms).

In large doses sympathomimetics may give rise to giddiness, headache, nausea, vomiting, sweating, thirst, tachycardia, precordial pain, palpitations, difficulty in micturi-tion, muscular weakness and tenseness, anxiety, restlessness, and insomnia. Many patients can present a toxic psychosis with delusions and hallucinations. Some may develop cardiac arrhythmias, circulatory collapse, convulsions, coma, and respiratory failure.

The oral LD 50 of the mixture of the two drugs in mature rats and mice was greater than 1700 mg/kg and 600 mg/kg, respectively.

Treatment --The patient should be induced to vomit, even if emesis has occurred spontaneously. Pharmacologically induced vomiting by the administration of ipecac syrup is a preferred method. However, vomiting should not be induced in patients with impaired consciousness. The action of ipecac is facilitated by physical activity and by the administration of eight to twelve fluid ounces of water. If emesis does not occur within 15 minutes, the dose of ipecac should be repeated. Precautions against aspiration must be taken, especially in infants and children. Following emesis, any drug remaining in the stomach may be absorbed by activated charcoal administered as a slurry with water. If vomiting is unsuccessful or contraindicated, gastric lavage should be performed. Isotonic and one-half isotonic saline are the lavage solutions of choice. Saline cathartics, such as milk of magnesia, draw water into the bowel by osmosis and therefore may be valuable for their action in rapid dilution of bowel content. Dialysis is of little value in antihistamine poisoning. After emergency treatment the patient should continue to be medically monitored.

Treatment of the signs and symptoms of overdosage is symptomatic and supportive. Stimulants (analeptic agents) should not be used. Vasopressors may be used to treat hypotension. Short-acting barbiturates, diazepam, or paraldehyde, may be administered to control seizures. Hyper-pyrexia, especially in children, may require treatment with tepid water sponge baths or a hypothermic blanket. Apnea is treated with ventilatory support.


RYNATAN® Tablets ARE NOT INTENDED FOR USE IN CHILDREN UNDER 12 YEARS OF AGE. The usual adult dosage is one tablet twice a day.


RYNATAN® Tablets contain 1 mg azatadine maleate and 120 mg pseudoephedrine sulfate. RYNATAN® Tablets are coral-colored, sugar-coated tablets branded in black with the product name (RYNATAN) and product identification numbers, 711, bottle of 100 (NDC 0037-0711-10).

Store between 2° and 30°C (36° and 86°F).


Key Pharmaceuticals, Inc.

Kenilworth, NJ 07033 USA



Division of Carter-Wallace, Inc.

Cranbury, NJ 08512

IN-0711-02                                     Rev. 4/99


NOTE: These photos can be used only for identification by shape, color, and imprint. They do not depict actual or relative size.

The product samples shown here have been supplied by the manufacturer and reproduced in full color by PDR as a quick-reference identification aid. While every effort has been made to assure accurate reproduction, please remember that any visual identification should be considered preliminary. In cases of poisoning or suspected overdosage, the drug' identity should be verified by chemical analysis.