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TUSSEND® SYRUP:
Each teaspoonful (5 mL) contains:
Hydrocodone Bitartrate, USP ............................. 2.5 mg
Pseudoephedrine Hydrochloride, USP ................. 30 mg
Chlorpheniramine Maleate, USP ........................... 2 mg
Alcohol, USP ........................................................ 5%
TUSSEND® SYRUP also contains: High Fructose Corn Syrup, Sucrose, Propylene Glycol, Flavor, Methylparaben, Saccharin Sodium, Propylparaben, FD&C Yellow No. 6, and Purified Water, USP.
TUSSEND® TABLETS:
Each tablet contains:
Hydrocodone Bitartrate, USP ............................... 5 mg
Pseudoephedrine Hydrochloride, USP ................. 60 mg
Chlorpheniramine Maleate, USP ........................... 4 mg
TUSSEND® TABLETS also contain: Lactose, Pregelatinized Starch, Croscarmellose Sodium, Silicon Dioxide, Magnesium Stearate and D & C Yellow #10.
Hydrocodone bitartrate is an opioid analgesic and antitussive and occurs as fine white, crystals or as crystalline powder. It is affected by light. The chemical name is 4,5(alpha)-epoxy-3-methoxy-17-methylmorphinan-6-one-tartrate (1:1) hydrate (2:5). Its structural formula is as follows:
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C 16 H 21 NO 3 ·C 4 H 6 O 6 ·2 1/2 H 2 O M.W. 494.50
Pseudoephedrine hydrochloride is an adrenergic (vasoconstrictor) which occurs as fine white to off-white crystals or powder, having a faint characteristic odor. It is very soluble in water, freely soluble in alcohol, and sparingly soluble in chloroform. The chemical name is benzenemethanol, (alpha)-[1-(methylamino)ethyl]- [S-(R*,R*)]-hydrochloride. Its structural formula is as follows:
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C
10
H
15
NO HCl
M.W. 201.70
Chlorpheniramine maleate is an antihistaminic that occurs as white, odorless, crystalline powder. Its solutions have a pH between 4 and 5. It is freely soluble in water, soluble in alcohol and in chloroform, and slightly soluble in ether and benzene. The chemical name is 2-pyridinepropanamine, (alpha)-(4-chlorophenyl)-N, N-dimethyl-(Z)-2-butenedioate (1:1). Its structural formula is as follows:
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C
16
H
19
CN
2
C
4
H
4
O
4
M.W. 300.07
Hydrocodone is a semi-synthetic narcotic antitussive with multiple actions qualitatively similar to those of codeine. Most of these involve the central nervous system and smooth muscle. The precise mechanism of action of hydrocodone and other opiates is not known; however, hydrocodone is believed to act directly on the cough center. In excessive doses, hydrocodone, like other opium derivatives, will depress respiration. The effects of hydrocodone in therapeutic doses on the cardiovascular system are insignificant. Hydrocodone can produce miosis, euphoria, physical and physiological dependence.
Following a 10 mg oral dose of hydrocodone administered to five adult male subjects, the mean peak concentration was 23.6 +/- 5.2 ng/mL. Maximum serum levels were achieved at 1.3 +/- 0.3 hours and the half-life was determined to be 3.8 +/- 0.3 hours. Hydrocodone exhibits a complex pattern of metabolism including O-demethylation, N-demethylation and 6-keto reduction to the corresponding 6-(alpha)- and 6-(beta)-hydroxymetabolites.
Pseudoephedrine acts as an indirect sympathomimetic agent by stimulating sympathetic (adrenergic) nerve endings to release norepinephrine. Norepinephrine in turn stimulates alpha and beta receptors throughout the body. The action of pseudoephedrine hydrochloride is apparently more specific for the blood vessels of the upper respiratory tract and less specific for the blood vessels of the systemic circulation. The vasoconstriction elicited at these sites results in the shrinkage of swollen tissues in the sinuses and nasal passages. Pseudoephedrine is rapidly and almost completely absorbed from the gastrointestinal tract. Considerable variation in half-life has been observed (from about 45 minutes to 10 hours) which is attributed to differences in absorption and excretion. Excretion rates are also altered by urine pH, increasing with acidification and decreasing with alkalinization. As a result, mean half-life falls to about 4 hours at pH 5 and increases to about 12 to 13 hours at pH 8. After administration of a 60 mg tablet, 87 to 97% of the pseudoephedrine is cleared from the body within 24 hours. The drug is distributed to body tissues and fluids, including fetal tissue, breast milk, and the central nervous system.
About 55% to 75% of an administered dose is excreted unchanged in the urine; the remainder is apparently metabolized in the liver to inactive compounds by N-demethylation, parahydroxylation, and oxidative deamination.
Chlorpheniramine is an antihistamine that possesses anticholinergic and sedative effects. It is considered one of the most effective and least toxic of the histamine antagonists. Chlorpheniramine is a H 1 receptor antagonist. It antagonizes many of the pharmacologic actions of histamine. It prevents released histamine from dilating capillaries and causing edema of the respiratory mucosa. Chlorpheniramine is well absorbed and has a duration of action 4 to 6 hours. Its half-life in serum is 12 to 16 hours. Degradation products of chlorpheniramine's metabolic transformation by the liver are almost completely excreted in 24 hours.
TUSSEND® syrup and tablets are indicated for relief of cough and congestion due to colds, acute respiratory infections, laryngeal and pulmonary tuberculosis, acute and chronic bronchitis and hay fever. In addition TUSSEND® syrup and tablets helps relieve the sneezing and itching associated with hay fever.
Hypersensitivity to any of the ingredients. Patients known to be hypersensitive to other sympathomimetic amines may exhibit cross sensitivity with pseudoephedrine. Sympathomimetic amines are contraindicated in patients with severe coronary artery disease, and patients on monoamine oxidase (MAO) inhibitor therapy.
Antihistamines are contraindicated in patients with narrow-angle glaucoma, urinary retention, peptic ulcer, during an asthmatic attack and in patients receiving MAO inhibitors.
TUSSEND® syrup and tablets should not be administered to pre-mature or full-term infants. TUSSEND® syrup and tablets are contraindicated in nursing mothers because of the higher than usual risk for infants from sympathomimetic amines.
General: Sympathomimetic amines should be used with caution in patients with hypertension, ischemic heart disease, diabetes mellitus, increased intraocular pressure, hyperthyroidism, or prostatic hypertrophy. Sympathomimetics may produce central nervous system stimulation with convulsions or cardiovascular collapse with accompanying hypotension. DO NOT EXCEED RECOMMENDED DOSAGE.
Hypertensive crises can occur with concurrent use of pseudoephedrine and monoamine oxidase (MAO) inhibitors, indomethacin, or with beta blockers and methyldopa. If a hypertensive crisis occurs, these drugs should be discontinued immediately and therapy to lower blood pressure should be instituted. Fever should be managed by means of external cooling.
Chlorpheniramine has an atropine-like action and should be used with caution in patients with increased intraocular pressure, cardiovascular disease, hypertension or in patients with a history of bronchial asthma.
Head Injury and Increased Intracranial Pressure: The respiratory depressant effects of narcotics and their capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions or a pre-existing increase in intracranial pressure. Furthermore, narcotics produce adverse reactions which may obscure the clinical course of patients with head injuries.
Acute Abdominal Conditions: The administration of narcotics may obscure the diagnosis or clinical course of patients with acute abdominal conditions.
Special Risk Patients: As with any narcotic, TUSSEND® syrup and tablets should be used with caution in elderly or debilitated patients and those with severe impairment of hepatic or renal function, hypothyroidism, Addison' disease, prostatic hypertrophy or urethral stricture. The usual precautions should be observed and the possibility of respiratory depression should be kept in mind.
Information for Patients: Narcotics and antihistamines may impair the mental and physical abilities required for the performance of potentially hazardous tasks, such as driving a vehicle or operating machinery. Patients should also be warned about the possible additive effects with alcohol and other central nervous system depressants (hypnotics, sedatives, tranquilizers).
Drug Interactions: Patients receiving other narcotics, antipsychotics, antianxiety agents or other CNS depressants (including alcohol) concomitantly with TUSSEND® syrup and tablets may exhibit additive CNS depression. When combined therapy is contemplated, the dose of one or both agents should be reduced. The use of MAO inhibitors or tricyclic antidepressants with hydrocodone preparations may increase the effect of either the antidepressant or hydrocodone.
The concurrent use of anticholinergics with hydrocodone may produce paralytic ileus.
Beta-adrenergic blockers and MAO inhibitors may potentiate the pressor effects of pseudoephedrine. Concurrent use of digitalis glycosides may increase the possibility of cardia arrhythmias. Sympathomimetics may reduce the hypotensive effects of guanethidine, mecamylamine, methyldopa, reserpine, and veratrum alkaloids. Concurrent use of tricyclic antidepressants may antagonize the effects of pseudoephedrine.
Laboratory Test Interactions: Antihistamines may suppress the wheal and flare reactions to antigen skin testing. Considerable interindividual variation in the extent and duration of suppression have been reported, depending on the antigen and test technique, antihistamine and dosage regimen, time since the last dose and individual response to testing. In one study, usual oral dosages of chlorpheniramine suppressed the wheal response for about 2 days after the last dose. Whenever possible antihistamines should be discontinued about 4 days prior to skin testing procedures since they may prevent otherwise positive reactions to dermal reactivity indicators.
Carcinogenesis, Mutagenesis and Impairment of Fertility: No long term or reproduction studies in animals have been performed with TUSSEND® syrup or tablets to evaluate its carcinogenic, mutagenic and impairment of fertility potential.
Usage In Pregnancy: Teratogenic Effects: Pregnancy Category C. Hydrocodone has been shown to be teratogenic in hamsters when given in doses 700 times the human dose. There are no adequate and well-controlled studies in pregnant women. TUSSEND® syrup or tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nonteratogenic Effects: Babies born to mothers who have been taking opioids regularly prior to delivery will be physically dependent. The withdrawal signs include irritability and excessive crying, tremors, hyperactive reflexes, increased respiratory rate, increased stools, sneezing, yawning, vomiting and fever. The intensity of syndrome does not always correlate with the duration of maternal opioid use or dose. There is no consensus on the best method of managing withdrawal. Chlorpromazine 0.7-1.0 mg/kg q6h, and paregoric 2-4 drops q4h, have been used to treat withdrawal symptoms in infants. The duration of therapy is 4 to 28 days, with the dosage decreased as tolerated.
Labor and Delivery: As with all narcotics administration of TUSSEND® syrup or tablets to the mother shortly before delivery may result in some degree of respiratory depression in the newborn, especially if higher doses are used.
Nursing Mothers: TUSSEND® syrup and tablets are contraindicated in nursing mothers because of the higher than usual risk infants with sympathomimetic amines.
Pediatric Use: Antihistamines may cause excitability, especially in children. Do not exceed recommended dosage because at higher doses nervousness, dizziness or sleeplessness may occur.
In young children, as well as adults, the respiratory center is sensitive to the depressant action of narcotic cough suppressants in a dose-dependent manner. Benefit to risk ratio should be carefully considered especially in children with respiratory embarrassment (e.g., croup).
Use in the Elderly: The elderly (60 years and older) are more likely to have adverse reactions to sympathomimetics. Overdose of sympathomimetics in this age group may cause hallucinations, convulsions, CNS depression and death.
Hydrocodone Bitartrate: The most frequently observed adverse reactions include lightheadedness, dizziness, sedation, nausea and vomiting. These effects seem to be more prominent in ambulatory patients than in nonambulatory patients and some of these adverse reactions may be alleviated if the patient lies down.
Other adverse reactions include:
Central Nervous System: Drowsiness, mental clouding, lethargy, impairment of mental and physical performance, anxiety, fear, dysphoria, psychic dependence, mood changes.
Gastrointestinal System: Prolonged administration may produce constipation.
Genitourinary System: Urethral spasm, spasm of vesical sphincters and urinary retention have been reported.
Pseudoephedrine Hydrochloride: Pseudoephedrine may cause mild central nervous system stimulation, especially in those patients who are hypersensitive to sympathomimetic drugs. Nervousness, excitability, restlessness, dizziness, weakness and insomnia may also occur. Headache and drowsiness have also been reported. Large doses may cause lightheadedness, nausea and/or vomiting. Sympathomimetic drugs have also been associated with certain untoward reactions including fear, anxiety, tenseness, restlessness, tremor, weakness, pallor respiratory difficulty, dysuria, insomnia, hallucination, convulsion, CNS depression, arrhythmias and cardiovascular collapse with hypotension.
Chlorpheniramine Maleate: Slight to moderate drowsiness may occur and is the most frequent side effect.
Other possible side effects of antihistamines in general include:
General: Urticaria, drug rash, anaphylactic shock, photosensitivity, excessive perspiration, chills, dryness of the mouth, nose and throat.
Cardiovascular: Hypotension, headache, palpitation, tachycardia extrasystoles.
Hematological: Hemolytic anemia, thrombocytopenia and agranulocytosis.
CNS: Sedation, dizziness, disturbed coordination, fatigue, confusion, restlessness, excitation, nervousness, tremor, irritability, insomnia, euphoria, paresthesia, blurred vision, dipiopia, vertigo, tinnitus, hysteria, neuritis, convulsion.
Gastrointestinal: Epigastric distress, anorexia, nausea, vomiting, diarrhea, constipation.
Genitourinary: Urinary frequency, difficult urination, urinary retention, early menses.
Respiratory: Thickening of bronchial secretions, tightness of chest, wheezing and nasal stuffiness.
TUSSEND® syrup and tablets are subject to the Federal Controlled Substances Act (Schedule III).
Psychic dependence and tolerance may develop upon repeated administration of narcotics; therefore, TUSSEND® syrup and tablets should be prescribed and administered with caution. However, psychic dependence is unlikely to develop when TUSSEND® syrup or tablets are used for a short time.
Physical dependence, the condition in which continued administration of the drug is required to prevent the appearance of a withdrawal syndrome, assumes clinically significant proportions only after several weeks of continued narcotic use, although some mild degree of physical dependence may develop after a few days of narcotic therapy. Tolerance, in which increasingly large doses are required to produce the same degree of effectiveness, is manifested initially by a shortened duration of effect, and subsequently by decreases in the intensity of the effect. The rate of development of tolerance varies among patients.
Signs and Symptoms: Hydrocodone: Serious overdosage with hydrocodone is characterized by respiratory depression (a decrease in respiratory rate and/or tidal volume, Cheyne Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. In severe overdosage, apnea, circulatory collapse, cardiac arrest and death may occur.
Pseudoephedrine: Overdosage with pseudoephedrine can cause excessive central nervous system stimulation resulting in excitement, nervousness, anxiety, tremor, restlessness and insomnia. Other effects include tachycardia, hypertension, pallor, mydriasis, hyperglycemia and urinary retention. Severe overdosage may cause tachypnea, or hyperpnea, hallucinations, convulsion, or delirium, but in some individuals there may be central nervous system depression with somnolence, stupor, or respiratory depression. Arrythmias (including ventricular fibrillation) may lead to hypotension and circulatory collapse. Severe hypokalemia can occur, probably due to compartmental shift rather than depletion of potassium. No organ damage or significant metabolic arrangement is associated with pseudoephedrine overdosage. The toxic and lethal concentration in human biologic fluids are not known. Excretion rates increase with urine acidification and decrease with alkalinization. Few reports of toxicity due to pseudoephedrine have been published, and no case of fatal overdosage is known.
Chlorpheniramine: Manifestations of antihistamine overdosage may vary from central nervous system depression (sedation, apnea, cardiovascular collapse) to stimulation (insomnia, hallucinations, tremors or convulsions). Other signs and symptoms may be dizziness, tinnitus, ataxia, blurred vision and hypotension. Stimulation is particularly likely in children, as are atropine-like signs and symptoms (dry mouth, dilated pupils, flushing, hyperthermia, and gastrointestinal symptoms).
Treatment: Primary attention should be given to the re-establishment of adequate respiratory exchange through provision of a patent airway and the institution of assisted or controlled ventilation. The narcotic antagonist naloxone is a specific antidote against respiratory depression which may result from overdosage or unusual sensitivity to narcotics including hydrocodone. Therefore, an appropriate dose of naloxone hydrochloride (see package insert) should be administered, preferably by the intravenous route and simultaneously with efforts at respiratory resuscitation. Since the duration of action of hydrocodone may exceed that of the antagonist, the patient should be kept under continued surveillance and repeated doses of the antagonist should be administered as needed to maintain adequate respiration.
An antagonist should not be administered in the absence of clinically significant respiratory or cardiovascular depression. Oxygen, intravenous fluids, vasopressors and other supportive measures should be employed as indicated.
Gastric emptying may be useful in removing unabsorbed drug.
The patient should be induced to vomit even if emesis has occurred spontaneously; however, vomiting should not be induced in patients with impaired consciousness. Precautions against aspiration should be taken, especially in infants and children.
Ipecac syrup is the preferred method for inducing vomiting. The action of ipecac is facilitated by physical activity and the administration of eight to twelve fluid ounces of water. If emesis does not occur within fifteen minutes, the dose of ipecac should be repeated. 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 solution 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.
Treatment of the signs and symptoms of overdosage is symptomatic and supportive. Vasopressors may be used to treat hypotension. Short-acting barbiturates diazepam or paraldehyde may be administered to control seizures.
Hyperpyrexia, especially in children, may require treatment with tepid water sponge baths or a hypothermic blanket. Apnea is treated with ventilatory support. Stimulants (analeptic agents) should not be used.
TUSSEND® SYRUP
ADULTS: Two teaspoonfuls (10mL) every 4-6 hours. CHILDREN: 6-12 years: One teaspoonful (5mL) every 4-6 hours. Do not exceed four doses in a 24 hour period.
TUSSEND® TABLETS
ADULTS: 1 tablet every 4-6 hours. CHILDREN: 6-12 years: 1/2 tablet every 4-6 hours. Do not exceed four doses in a 24 hour period.
TUSSEND® SYRUP is supplied as a clear yellow liquid, banana-flavored, in bottles of one pint (16 fl. oz.), NDC 61570-004-16.
TUSSEND® TABLETS are yellow, scored, capsule shaped with a MPC100 identification number.
Bottles of 100 ................................. NDC 61570-011-01
Storage Store at controlled room temperature, 15°-30°C (59°-86°F).
Dispense in a tight, light-resistant container as described in USP.
Rx only
A Schedule CIII Controlled Substance.
Manufactured for: Monarch Pharmaceuticals, Inc., Bristol, TN 37620
Manufactured by: King Pharmaceuticals, Inc., Bristol, TN 37620
0931880
Revised 8/96