Dehistine

Phenylephrine, a sympathomimetic amine acts directly on α-adrenergic receptors in the mucosa of the respiratory tract to produce vasoconstriction that increases peripheral resistance, resulting in an increase in both systolic and diastolic blood pressure. Accompanying the pressor response is a marked reflex bradycardia due to increased vagal activity. It produces vasoconstriction that lasts longer than that produced by ephedrine and epinephrine, and in therapeutic doses, produces little or no central nervous system (CNS) stimulation. Phenylephrine has reduced bioavailability from the gastrointestinal tract because of first pass metabolism by the liver.

Chlorpheniramine maleate competitively antagonizes most of the smooth muscle stimulating actions of histamine on the H1 receptors of the GI tract, uterus, large blood vessels, and bronchial muscle. It also antagonizes the action of histamine that results in increased capillary permeability and the formation of edema. Chlorpheniramine maleate is an alkylamine-type antihistamine. This group of antihistamines are among the most active histamine antagonists and are generally effective in relatively low doses. They thereby prevent, but do not reverse, responses mediated by histamine alone. The anticholinergic actions of most antihistamines provide a drying effect on the nasal mucosa. These drugs are not so prone to produce drowsiness and are among the most suitable agents for daytime use, but a significant proportion of patients do experience this effect.

Methscopolamine Nitrate is one of the principal anticholinergic/antispasmodic components of belladonna alkaloids that exhibits antisecretory activity. Methscopolamine inhibits the muscarinic actions of acetylcholine on structures innervated by postganglionic cholinergic nerves: smooth muscle, cardiac muscle, sinoatrial and atrioventricular nodes, and exocrine glands. In general, the smaller doses of anticholinergics inhibit salivary and bronchial secretions, sweating, and accommodation; cause dilation of the pupil; and may affect the heart rate.

Patient consultation should include the following information regarding proper use of this medication:
• Do not take more medication than the amount recommended.
• This medication should be used with caution during exercise or hot weather, overheating may result in heat
 stroke.
• Do not drive or operate machinery if drowsiness or dizziness occurs.
• Do not ingest alcoholic beverages, monoamine oxidase (MAO) inhibitors, or CNS depression-
  producing medications (hypnotics, sedatives, tranquilizers) while taking this medication.
• This medication possibly increases sensitivity of eyes to light.
• Methscopolamine nitrate may cause blurred vision.
• If a dose is missed, the medication should be taken as soon as possible unless it is almost time for the next
 dose.  Do not double doses.
• This medication should be stored in a tight, light-resistant container at temperatures between 15°-30°C (59°-86°F).
• Keep all medications out of reach of children.  In case of accidental overdose, seek professional assistance
or contact a poison control center immediately.
Caution patients about the signs of potential side effects, especially:
• Anticholinergic effects – clumsiness or unsteadiness; severe drowsiness; severe dryness of mouth, nose, or
throat; flushing or redness of face; shortness of breath or trouble breathing.
• Blood dyscrasias-sore throat and fever; unusual bleeding or bruising; unusual tiredness or weakness.
• Fast or irregular heartbeat.
• Psychotic episodes.
• Tightness in chest.

Note:  When anticholinergics are given to patients, especially children, where the environmental temperature is high there is
a risk of a rapid increase in body temperature because of suppression of sweat gland activity.  Infants, patients with Down’s syndrome,
and children with spastic paralysis or brain damage may show an increased response to anticholinergics, thus increasing the potential for
side effects.

Geriatric or debilitated patients may respond to usual doses of anticholinergics with excitement, agitation, drowsiness, or confusion.

The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on conditions):
Blood pressure determination – recommended at frequent intervals during therapy:  Electrocardiogram (ECG) – monitoring may be required:
Intraocular pressure determination – recommended at periodic intervals, as these medications may increase the intraocular pressure.

Do not take this product if you are presently taking, or have taken within the preceding two weeks, a prescription drug for high blood pressure or depression without first consulting your physician. Absorption of other oral medications may be decreased during concurrent use with anticholinergics due to decreased gastrointestinal motility and delayed gastric emptying.
Combinations containing any or the following medications, depending on the amount present, may also interact with this product:

• Alkalizers, such as: calcium and/or magnesium-containing antacids; Carbonic anhydrase inhibitors; citrates; sodium bicaronate-urinary excretion of anticholinergics may be delayed by alkalization of the urine, thus potentiating methscopolamine's therapeutic and/or side effects.
• α-adrenergic blocking agents or other medications with α-adrenergic blocking action - prior to administration of α-adrenergics may block the pressor response to phenylephrine, possibly resulting in severe hypotension; medications with α-adrenergic blocking action may decrease the pressor effect and shorten the duration of action of phenylephrine.
• Antacids or absorbent antidiarrheals-simultaneous use of these medications may reduce absorption of methscopolamine, resulting in decreased therapeutic effectiveness; doses of these medications should be spaced 2 or 3 hours apart from doses of methscopolamine.
• Anesthetics, hydrocarbon inhalation - Concurrent use of chloroform, cyclopropane, halothane, or trichloroethylene with phenylephrine may increase the risk of severe ventricular arrhythmias because these anesthetics greatly sensitize the myocardium to the effects of sympathomimetic amines; phenylephrine should be used with caution and in substantially reduced dosage in patients receiving these anesthetics. Enflurane, isoflurane, or methoxyflurane may also cause some sensitization of the myocardium to the effects of sympathomimetic amines.
• Anesthetics, parenteral-local - Phenylephrine should be used cautiously and in carefully circumscribed quantities, if at all, with local anesthetics for anesthetizing areas with end artieries (such as the finger, toes, or penis) or otherwise compromised blood supply; ischemia leading to gangrene may result.
• Anticholinergics - Concurrent use with anticholinergic effects; patients should be advised to report occurrence of gastrointestinal problems promptly since paralytic ileus may occur with concurrent therapy.
• Antidepressants, tricyclic or maprotiline - Concurrent use may potentiate the cardiovascular effects of phenylephrine, possible resulting in arrhythmias, tachycardia, or severe hypertension or hyperpyrexia.
  
• Antihypertensives, or diuretics used as - Antihypertensive effects may be reduced when these medications are used concurrently with phenylephrine; the patient should be carefully monitored to confirm that the desired effect is being obtained.
• β-adrenergic blocking agents - Therapeutic effects may be inhibited when these medications are used concurrently with phenylephrine, especially larger doses; also, β-adrenergic blockage may result in unopposed α-adrenergic activity with a risk of hypertension and excessive bradycardia with possible heart block.
• CNS Depressants - Concurrent use of alcohol, antihistamines with alcohol, tricyclic antidepressants, barbiturates and other CNS depressants may have an additive effect.
• Cocaine, mucosal-local - Concurrent use with phenylephrine may increase the cardiovascular effects of either or both medications and the risk of adverse side effects.
• Digitalis glycosides - Concurrent use with phenylephrine may increase the risk of cardiac arrhythmias; caution and ECG monitoring are necessary if concurrent use is required.
• Ergoloid mesylates or Ergotamine with phenylephrine may produce peripheral vascular ischemia and gangrene and is not recommended. Concurrent use of ergotamine with phenylephrine, resulting in possible severe hypertension and rupture of cerebral blood vessels.
• Doxapram - Concurrent use may increase the pressor effects of either doxapram or phenylephrine.
• Ketoconazole - Anticholinergics may increase gastrointestinal pH, possibly resulting in a marked reduction in ketoconazole absorption during concurrent use with anticholinergics; patients should be advised to take these medications at least 2 hours after ketoconazole.
• Methyldopa - In addition to possibly decreasing the hypotensive effects of these medications, concurrent use may enhance the pressor response to phenylephrine; caution is required with very small initial doses of methyldopa being administered.
• MAO inhibitors - Concurrent use may prolong and intensify cardiac stimulate and vasopressor effects of phenylephrine and chlorpheniramine, resulting in headache, cardiac arrhythmias, vomiting or sudden and severe hypertensive and/or hyperpyretic crisis. These medications should not be administered during or within 14 days following the administration of MAO inhibitor therapy.
• Metoclopramide - Concurrent use of metoclopramide with anticholinergics may antagonize metoclopramide's effects on gastrointestinal motility.
• Potassium chloride - Concurrent use with anticholinergics may increase the severity of potassium chloride-induced gastrointestinal lesions.
• Rauwolfia alkaloids - Concurrent use may prolong the direct-acting sympathomimetic amines by preventing the uptake into storage granules.
  

Antihistamines may interfere with diagnostic test results for skin tests using allergen extracts. Anticholinergics may
interfere with diagnostic test results for gastric acid secretion by antagonizing the effect of pantagastrin and histamine,
and for radionucleotide gastric emptying studies by delaying gastric emptying.

Use of antihistamines is not recommended in newborn or premature infants because this age group has an increased
susceptibility to anticholinergic side effects, such as CNS excitation, and an increased tendency toward convulsion.
In infants and children, overdosage may cause hallucinations, convulsions, and death.  A paradoxical reaction characterized
by hyperexcitability may occur in older children taking antihistamines.

Use is not recommended for children under six years of age.  Infants and young children with spastic paralysis or brain damage
since an increased response to anticholinergics are given to children where the environmental temperature because of the
suppression of sweat gland activity.  A paradoxical reaction characterized by hyperexcitability may occur in children taking
large doses of anticholinergics.

Appropriate studies with phenylephrine have not been performed in the pediatric population.

Confusion, hallucinations, seizures, and CNS depression may be more likely to occur in geriatric patients taking
sympathomimetic amines.  Geriatric patients may also be more sensitive to the effects, especially the vasopressor
effects, of sympathomimetic amines.  Confusion, dizziness, sedation, hypotension, hyperexcitability, and
anticholinergic side effects, such as dryness of mouth and urinary retention (especially in males), may be more
likely to occur in geriatric patients taking antihistamines.

Geriatric patients may respond to usual doses of anticholinergics with excitement, agitation, drowsiness, or confusion.
Geriatric patients are especially susceptible to the anticholinergic side effects, such as constipation, dryness of the
mouth, and urinary retention (especially in males).  If these side effects occur and continue or are severe, medication
should probably be discontinued.

Caution is also recommended when anticholinergics are given to geriatric patients, because of the danger of precipitating
undiagnosed glaucoma.  Memory may become severely impaired in geriatric patients, with the continued use of anticholinergics,
since these drugs block the action of acetylcholine, which is responsible for many functions of the brain, including memory function.

The labeling below represents the labeling currently used.

NDC 60258-220-16

Dehistine
    Syrup

Each teaspoonful (5 mL) contains:
Phenylephrine hydrochloride .....................10 mg
Chlorpheniramine Maleate.........................2 mg
Methscopolamine Nitrate...........................1.25 mg

SUGAR FREE/ALCOHOL FREE

              Rx Only

CYPRESS PHARMACEUTICAL, INC.

       16 fl oz (473 mL)

Labeling on Side Panel:

USUAL DOSAGE: Adults and children 12 years of age and older: 1-2 teaspoonfuls (5-10 mL) every 4 to 6 hours, not to exceed 8 teaspoonfuls in 24 hours. Children 6 to under 12 years of age: 1 teaspoonful (5 mL) every 4 to 6 hours, not to exceed 4 teaspoonfuls in 24 hours. Dehistine Syrup is not recommended for children under 6 years of age.

See package insert for full prescribing information.

KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN. IN CASE OF ACCIDENTAL OVERDOSE, SEEK PROFESSIONAL ASSISTANCE OR CONTACT A POISON CONTROL CENTER IMMEDIATELY

Store at controlled room temperature, 15o-30oC (59o-86oF). Avoid exposure to heat. Dispense in a tight, light-resistant container as defined in the USP/NF with a child-resistant closure.

Mfg. by: Great Southern Laboratories, Houston, TX 77099
Mfg. for: Cypress Pharmaceutical, Inc., Madison, MS 39110

L412 Rev. 01/09

Dehistine  phenylephrine hydrochloride, chlorpheniramine maleate, methscopolamine nitrate liquid

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:60258-220 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Phenylephrine Hydrochloride (Phenylephrine) Phenylephrine Hydrochloride 10 mg  in 5 mL Chlorpheniramine Maleate (Chlorpheniramine) Chlorpheniramine Maleate 2 mg  in 5 mL Methscopolamine Nitrate (Methscopolamine ) Methscopolamine Nitrate 1.25 mg  in 5 mL

Product Characteristics Color      Score      Shape Size Flavor ROOT BEER Imprint Code Contains

Packaging # Item Code Package Description 1 NDC:60258-220-16 473 mL in 1 BOTTLE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date unapproved other 07/24/2009

Labeler - Cypress Pharmaceutical, Inc. (790248942)

Registrant - Great Southern Laboratories (056139553)

Establishment
Name	Address	ID/FEI	Operations
Great Southern Laboratories		056139553	manufacture

Revised: 11/2009   Cypress Pharmaceutical, Inc.