DY-G Liquid

NDC 60258-371-16
Rx Only

DESCRIPTION:
DY-G Liquid is a bronchodilator/expectorant combination supplied as a clear, mint flavored, alcohol fee, dye free and gluten free liquid for oral administration.

Each teaspoonful (5 mL) contains:
Dyphylline............................................100 mg
Guaifenesin..........................................100 mg

Inactive ingredients: Glycerin, Propylene Glycol, Sorbitol, Sodium Saccharin, Sucrose, Spearmint Flavor, Purified Water.

Dyphylline is 7-(2,3-dihydroxypropyl)-theophylline, a white, extremely bitter, amorphous powder that is fully soluble in water and soluble in alcohol to the extent of 2 g/100 mL. Dyphylline forms a neutral solution that is stable in gastrointestinal fluids over a wide range of pH. It has the following chemical structure:

Guaifenesin is an expectorant which occurs as a white to slightly gray, crystalline powder, having a bitter taste. It may have a slight characteristic odor. It is soluble in water, alcohol, chloroform, glycerin, and propylene glycol. The chemical name is 3-(methoxyphenoxy)-1, 2-propanediol. It has the following chemical structure:

CLINICAL PHARMACOLOGY

Dyphylline is a xanthine derivative with pharmacological actions similar to theophylline and other members of this class of drugs. Its primary action is that of bronchodilation, but it also exhibits peripheral vasodilatory and other smooth muscle relaxant activity to lesser degree. The bronchodilatory action of dyphylline, as with other xanthines, is thought to be mediated through competitive inhibition of phosphodiesterase with a resulting increase in cyclic AMP producing relaxation of bronchial smooth muscle.

Dyphylline was reported to be the least toxic of seven theophylline derivatives, including the piperazine, N, N-diethylamino ethyl and the 2-hydroxy ethyl derivatives.1 The toxicity of dyphylline is only one-fifth that of aminophylline as determined intraperitoneally in mice, and onlyone-half as toxic in rates.2 Unlike the hydrolysable salts of theophylline, dyphylline is not converted to free theophylline in vivo. It is absorbed rapidlyin therapeutically active form and in healthy volunteers reaches a mean peak plasma concentration of 17.1 mcg/mL in approximately 45 minutes following a single oral dose of 1000 mg of dyphylline.

Dyphylline exerts its bronchodilatory effects directly and, unlike theophylline, is excreted unchanged by the kidneys without being metabolized by the liver. Because of this, dyphylline pharmackinetics and plasma levels are not influenced by various factors that affect liver function and hepatic enzyme activity, such as smoking, age, or concomitant use of drugs which affect liver function.

The elimination half-life of dyphylline is approximately two hours (1.8-2.1 hr) and approximately 88% of a single oral dose can be recovered from the urine unchanged. The renal clearance would be correspondingly reduced in patients with impaired function. In anuric patients, the half-life may be increased 3 to 4 times normal. Dyphylline plasma levels are dose-related and generally predictable. The therapeutic range of plasma levels with which dyphylline can be expected to produce effective bronchodilation has not been determined.

Dyphylline plasma concentrations can be accurately determined using high pressure liquid chromatography (HPLC) or gas-liquid chomatography (GLC). Guaifenesin is an expectorant whose action helps increase the output of thin respiratory tract fluid to facilitate mucociliary clearance and removal of inspissated mucus.

Guaifenesin is an expectorant which increases repiratory tract fluid secretions and helps to loosen phlegm and bronchial secretions. By reducing the viscosity of secretions, guaifenesin increases the efficiency of the cough reflex and of ciliary action in removing accumulated secretions from the trachea and bronchi. Guaifenesin is readily absorbed from the gastrointestinal tract and is rapidly metabolized and excreted in the urine. Guaifenesin has a plasma half-life of one hour. The major urinary metabolite is p-(2methoxyphenoxy) lactic acid.

INDICATIONS AND USAGE:

DY-G Liquid is indicated as a bronchodilator-expectorant for treating bronchial asthma, emphysema, bronchitis, pneumonitis and other related bronchopulmonary insufficiency conditions. DY-G Liquid acts to dilate bronchioles and liquefy mucus, giving relief from dyspnea, non-productive cough and tracheobronchial irritation.

CONTRAINDICATIONS:

As with other theophylline-type drugs, combining dyphylline with ephedrine or other sympathommetic drugs can cause excessive CNS stimulation. Such combinations are contraindicated in children unless accompanied by sufficient sedation to prevent undue CNS stimulation.

WARNINGS

This product is not indicated in the management of status asthmaticus, which is a serious medical emergency.

Although the relationship between plasma levels of dyphylline and appearance of toxicity is unknown, excessive doses may be expected to be associated with an increased risk of adverse effects.

PRECAUTIONS:

General: Use this product with caution in patients with severe cardiac disease, hypertension, glaucoma, hypothyroidism, severe renal and hepatic disease, acute myocardial injury or peptic ulcer. Do not use in children under age 6. Do not exceed 3 mg of dyphylline per pound of body weight daily in older children. Because the xanthines also act as diuretics, special precaution regarding hydration and avoidance of acidosis should be observed in children. The long term use of xanthine derivatives may result in a cumulative effect with increase in adverse reactions, as well as the development of tolerance.

Drug Interactions:

Synergism, between xanthine bronchodilators (e.g., theophylline), ephedrine and other sympathomemetic bronchodilators has been reported. This should be considered whenever these agents are prescribed concomitantly. Concurrent administration of dyphylline and probenecid, which competes for tubular secretion, as been shown to increase plasma half-life and dyphylline (see Clinical Pharmacology).

Carcinogenesis, Mutagenesis, Impairment of Fertility:

No long-term studies have been performed with this product.

Pregnancy:

Teratogenic effects-Pregnancy Category C.
Animal reproduction studies have not been conducted with this formulation. It is also not known whether this product can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. This medication should be given to pregnant women only if clearly needed.

Nursing Mothers:

Dyphylline is present in human milk approximately twice the maternal plasma concentration. Caution should be exercised when this product is administered to a nursing woman.

Pediatric Use:

Safety and effectiveness in children below the age of six have not been established. Use caution when administering to children six years of age or older.

ADVERSE REACTIONS

This formulation may cause nausea, headache, cardiac palpitation and CNS stimulation. Postprandial administration may help avoid gastric discomfort.

The following adverse reactions which have been reported with other xanthine bronchodilators, and which have most often been related to excessive drug plasma levels, should be considered as potential adverse effects when dyphylline is administered.

Gastrointestinal: nausea, vomiting, epigastric pain, hematemesis, diarrhea.

Central Nervous System: headache, irritability, restlessness, insomnia, hyperexcitability, agitation, muscle twitching, generalized clonic and tonic convulsions.

Cardiovascular: palpitation, tachycardia, extrasystoles, flushing, hypotension, circulatory failure, ventricular arrhythmias.

Respiratory: tachypnea

Renal: albuminuria, gross and microscopic hematuria, diuresis.

Other: hyperglycemia, inappropriate ADH syndrome.

Large doses of Guaifenesin may produce emesis but gastrointestinal upset at ordinary dosage levels is rare.

OVERDOSAGE

Signs and Symptoms: Restlessness, anorexia, nausea, vomiting, diarrhea, insomnia, irritability, and headache are typical symptoms resulting from a xanthine drug overdose. Marked overdosage with resulting severe vomiting, dehydration, excessive thirst, tinnitus, cardiac arrhythmias, hyperthermia, diaphoresis, and generalized clonic and tonic convulsions. Cardiovascular collapse has also occurred, with some fatalities. Seizures have occurred in some cases associated with very high theophylline plasma concentrations, without any premonitory symptoms of toxicity.

Treatment: There is no specific antidote for overdosage with drugs of the xanthine class. Symptomatic treatment and general supportive measures should be instituted with careful monitoring and maintenance of vital signs, fluids and electrolytes. The stomach should be emptied by inducing emesis if the patient is conscious and responsive, or by gastric lavage, taking care to protect against aspiration, especially in stuporous or comatose patients. Maintenance of an adequate airway is essential in case oxygen or assisted respiration is needed. Sympathomimetic agents should be avoided but sedatives such as short acting barbiturates may be useful.

Dyphylline is dialyzable and although not recommended as routine procedure in overdosage cases, hemodialysis may be of some benefit with severe intoxication is present or when the patient has not responded to general supportive and symptomatic treatment.

DOSAGE AND ADMINISTRATION:

The usual adult dose is 1 or 2 teaspoonfuls of liquid 3 or 4 times a day. In severe cases, dosage may be doubled or tripled if necessary. Maintenance dosage should be adjusted according to patient response.

USE IN CHILDREN:

Although pediatric dosages of dyphylline are established, no firm dosage for a combination of dyphylline and guaifenesin USP can be recommended for children under the age of six. Dosage for children over six may be calculated on the basis of 2 to 3 mg of dyphylline per pound of body weight daily in divided doses.

HOW SUPPLIED:

DY-G Liquid is supplied as a clear, mint flavored, alcohol free, dye free and gluten free liquid in pint bottles, NDC 60258-371-16.

Rx Only

WARNING:

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.

STORAGE:

Store at controlled room temperature 20° - 25°C (68° - 77°F); excursions permitted to 15°C - 30°C (59° - 86°F). [See USP Controlled Room Temperature.]

Tamper evident by foil seal under cap. Do not use if foil seal is broken or missing.

REFERENCES: 1Quevauviller and Morin: Press Med. 61, 1480, 1953. 2Kjell, Briseid and Jensen: "Respective Toxicity of Dihydroxpropyl
Theophylline and Teophylline Ethylene Diamine on the Mouse," Archiv for Parmacie Og. Chemi. 56, 741-9, 1949.

Manufactured for:
Cypress Pharmaceutical, Inc.
Madison, MS 39110

I119 Rev. 05/10

Product Packaging:

The packaging below represents labeling currently label:

Principal Display Panel and Side Panel for 473 mL label:

NDC 60258-371-16

Dy-G Liquid

BRONCHODILATOR/EXPECTORANT

Each teaspoonful (5mL) for oral administration contains:

Dyphylline.........................................100 mg
Guaifenesin.......................................100 mg

ALCOHOL FREE/DYE FREE/GLUTEN FREE

Rx Only

CYPRESS PHARMACEUTICAL, INC.

16 fl oz (473 mL)

DOSAGE AND ADMINISTRATION
The usual adult dose is 1 or 2 teaspoonfuls of liquid 3 or 4 times a day.
In severe cases, dosage may be doubled or tripled if necessary.
Maintenance dosage should be adjusted according to patient response.

Se attached insert for full prescribing information.

WARNING: KEEP THIS AND ALL MEDICATION 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 20° - 25°C (68° - 77°F); excursions permitted to 15° - 30°C (59° - 86°F). [See USP Controlled Room Temperature.]

Tamper evident by foil seal under cap. Do not use if foil seal is broken or missing.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088 (Toll Free).

Mfg. for: Cypress Pharmaceuticals, Inc., Madison, MS 39110

L639 Rev. 05/10

DY G
dyphylline, guaifenesin liquid

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	NDC Product Code (Source)	60258-371
Route of Administration	ORAL	DEA Schedule

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
Dyphylline (Dyphylline)	Dyphylline	100 mg in 5 mL
Guaifenesin (Guaifenesin)	Guaifenesin	100 mg in 5 mL

Inactive Ingredients
Ingredient Name	Strength
No Inactive Ingredients Found

Product Characteristics
Color		Score
Shape		Size
Flavor	MINT	Imprint Code
Contains

Packaging
#	NDC	Package Description	Multilevel Packaging
1	60258-371-16	473 mL In 1 BOTTLE	None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
unapproved drug other		10/31/2001

Labeler - Cypress Pharmaceutical, Inc. (790248942)

Revised: 06/2010Cypress Pharmaceutical, Inc.