ENDACOF DH
-
dihydrocodeine bitartrate,
brompheniramine maleate and
phenylephrine hydrochloride liquid
Larken Laboratories, Inc.
Disclaimer: This drug has not been found by FDA to be safe and effective, and this labeling has not been approved by FDA. For further information about unapproved drugs, click here.
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DESCRIPTION
Each 5 mL (one teaspoonful) for oral administration contains:
|
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| Dihydrocodeine Bitartrate* | 3 mg |
| Brompheniramine Maleate | 4 mg |
| Phenylephrine Hydrochloride | 7.5 mg |
ENDACOF-DH Oral Liquid also contains: Sodium benzoate, Citric acid, Saccharin sodium, Propylene glycol, Sorbitol, Flavor and Purified water.
Dihydrocodeine Bitartrate is an antitussive with the chemical name (Morphinan-6-ol 4, 5α-Epoxy-3-methoxy-17-methylmorphinan-5α, 6α )=2,3=dihydroxybutanedioate (1:1) (salt) an odorless, fine white powder is an opioid analgesic. It has the following structural formula:
C18H23NO3•C4H6O6 M. W. 451.47
Brompheniramine Maleate is an antihistamine having the chemical name, 2-Pyridinepropanamine, γ-(4-bromophenyl)-N, N-dimethyl-, (±)-,(Z)-2-butenedicate (1:1), with the following structure:
C16H19BrN2-C4H4O4 M. W. 435.31
Phenylephrine hydrochloride is an orally effective nasal decongestant. Chemically it is (-)-m-Hydroxy-α-[(methylamino) methyl]benzyl alcohol hydrochloride. Its chemical structure is as follows:
C9H13NO2-HCl M. W. 203.67
CLINICAL PHARMACOLOGY
Dihydrocodeine is a semi-synthetic narcotic analgesic related to codeine, with multiple actions qualitatively similar to those of codeine; the most prominent of these involve the central nervous system and organs with smooth muscle components. Brompheniramine Maleate is an alkylamine type antihistamine. This group of antihistamines is among the most active histamine antagonists and is generally effective in relatively low doses. The 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. Phenylephrine HCl is a sympathomimetic, which acts predominately on alpha-receptors and has little action on beta-receptors. It therefore functions as an oral nasal decongestant with minimal CNS stimulation.
INDICATIONS AND USAGE
ENDACOF-DH Oral Liquid is indicated to control cough and provide for temporary relief from congestion associated with the upper respiratory tract.
CONTRAINDICATIONS
This combination product is contraindicated in patients with hypersensitivity to Dihydrocodeine, codeine, or any of the active and inactive components listed above, or in any situation where opiods are contraindicated including significant respiratory depression (in unmonitored settings or in the absence of resuscitation equipment), acute or severe bronchial asthma or hypercapnia, and paralytic illeus. Antihistamines and sympathomimetics are contraindicated in patients receiving antihypertensive or antidepressant drugs containing monoamine oxidase (MAO) inhibitors. Antihistamines should not be used to treat lower respiratory tract symptoms or be given to premature or newborn infants Sympathomimetic agents are contraindicated in patients with severe hypertension, severe coronary artery disease, patients with narrow angle glaucoma, bronchial asthma, urinary retention, peptic ulcer, and during an asthma attack. This product is contraindicated in women who are pregnant.
WARNINGS
General
Considerable caution should be exercised in patients with hypertension, diabetes mellitus, ischemic heart disease, hyperthyroidism, increased intraocular pressure and prostatic hypertrophy. The elderly (60 years and older) are more likely to exhibit adverse reactions. Antihistamines may cause excitability, especially in children. At dosages higher than the recommended dose, nervousness, dizziness, or sleeplessness may occur.
Usage in Ambulatory Patients
Dihydrocodeine may impair the mental and/or physical abilities required for the performance of potentially hazardous takes such as driving a car or operating machinery.
Respiratory Depression
Respiratory depression is the most dangerous acute reaction produced by opiods agonist preparations, although it is rarely severe with usual doses. Oipiods decrease the respiratory rate, tidal volume, minute ventilation, and sensitivity to carbon dioxide. Respiratory depression occurs most frequently in elderly more debilitated patients, usually after large initial doses in non-tolerant patients, or when opiods are given in conjunction with other agents that depress respiration. This combination of products should be used with caution in patients with significant chronic obstructive pulmonary disease or cor pulmonale and in patients with a substantially decreased respiratory reserve, hypoxia hypercapnia, or respiratory depression.
Hypotensive Effect
Dihydrocodeine, like all opioid analgesics, may cause hypotension in patients whose ability to maintain blood pressure has been compromised by a depleted blood volume or who receive concurrent therapy with drugs such as phenothiazines or other agents which compromise vasomotor tone. ENDACOF-DH Oral Liquid may produce orthostatic hypotension in ambulatory patients. This combination product should be administered with caution to patients in circulatory shock, since vacillation produced by the drug may further reduce cardiac output and blood pressure.
Dependence
Dihydrocodeine can produce drug dependence of the codeine type and has the potential of being abused. This product should be prescribed and administered with the appropriate degree of caution. (See Drug Abuse and Dependence section).
PRECAUTIONS
General
This combination product should be used with caution in elderly or debilitated patients or those with any of the following conditions; adrenocortical insufficiency (e.g., Addison's disease); asthma; central nervous system depression or coma; chronic obstructive pulmonary disease; decreased respiratory reserve (including emphysema, severe obesity, cor pulmonale, or kyphoscoliosis); delirium tremens; diabetes; head injury; hypotension; hypertension; increased intracranial pressure; myxedema or hypothyroidism; prostatic hypertrophy or urethral stricture; and toxic psychosis. The benefits and risks of opiods in patients taking monoamine oxidase inhibitors and in those with a history of drug abuse should be carefully considered. This combination product may aggravate convulsions in patients with convulsive disorders, and, like all opiods, may induce or aggravate seizures in some clinical settings.
DRUG INTERACTIONS
General
Sympathomimetics may reduce the antihypertensive effects of methyldopa, mecamylamine, reserpine and veratrum alkaloids.
Other Central Nervous System Depressants
Patients receiving other oipioid analgesics, sedatives or hypnotics, muscle relaxants, general anesthetics, centrally acting anti-emetics, phenothiazines or other tranquilizers, or alcohol concomitantly with this combination product may exhibit additive depressant effects on the central nervous system. When such combined therapy is contemplated, the dose of one or both agents should be reduced. Concomitant use of Dihydrocodeine and antihistamines with alcohol and other CNS depressants may have an additive effect.
Monoamine Oxidase Inhibitors
Dihydrocodeine, like all opioids interact with monoamine oxidase inhibitors causing central nervous system excitation and hypertension. MAO inhibitors and beta-adrenergic blockers increase the effects of sympathomimetics. They may also prolong and intensity the anticholinergic effects of antihistamines.
Information for Patient/Caregivers
Patients receiving ENDACOF-DH Oral Liquid should be given the following information:
- Patients should be advised that ENDACOF-DH Oral Liquid may impair the mental or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery.
- Patients should be advised to report adverse experiences occurring during therapy.
- Patients should be advised not to adjust the dose of ENDACOF-DH Oral Liquid without consulting the prescribing professional.
- Patients should not combine ENDACOF-DH Oral Liquid with alcohol or other central nervous system stimulants.
- Women of childbearing potential who become, or are planning to become pregnant should be advised to consult their physician regarding the effects of opioids and other drug use during pregnancy on themselves and their unborn child
Patients should be advised that ENDACOF-DH Oral Liquid is a potential drug of abuse. They should protect it from theft, and it should never be given to anyone other than the individual for whom it was prescribed.
Pregnancy
Teratogenic Effects – Pregnancy Category C
Animal reproduction studies have not been conducted with ENDACOF-DH Oral Liquid. It is also not known whether this combination product can cause fetal harm when administered to pregnant women or can affect reproduction capacity in males and females. This combination product should be given to pregnant women only if clearly needed, especially during the first trimester.
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 the 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, Phenobarbital 2 mg/kg q6h, and paregoric 24 drops/kg q4h, have been used to treat withdrawal symptoms in infants. The duration of therapy is 4 to 28 days, with the dosages decreased as tolerated.
Labor and delivery
ENDACOF-DH Oral Liquid is not recommended for use by women during and immediately before labor and delivery because oral opioids may cause respiratory depression in the newborn.
Pediatric Use
This product is not recommended for use in children under 6 years of age. Children under two years may be more susceptible to the respiratory arrest, coma and death. Use of antihistamines is not recommended in infants. This age group may be at a higher risk than other age groups because of an increased susceptibility to anticholinergic effects, such as CNS excitation, and an increased tendency toward convulsions. In older children taking antihistamines, a paradoxical reaction characterized by hyperexcitability may occur. Very young ch8ildren may be more sensitive to the effects, especially the vasopressor effects of sympathomimetic amines.
Hepatic Impairment
ENDACOF-DH Oral Liquid should be given with caution to patients with hepatic insufficiency. Since dihydrocodeine is metabolized by the liver; the effects of this combination product should be monitored closely in such patients.
ADVERSE REACTIONS
The most frequently observed adverse reactions with dihydrocodeine include light-headedness, dizziness, drowsiness, headache, fatigue, sedation, sweating, nausea, vomiting, constipation, pruritus, and skin reactions. With the exception of constipation, tolerance develops to most of these effects. Other reactions that have been observed with dihydrocodeine or other opioids include respiratory depression, orthostatic hypotension, cough suppression, confusion, diarrhea, miosis, abdominal pain, dry mouth, indigestion, anorexia, spasm of biliary tract, and urinary retention. Physical and psychological dependence are possibilities. Hypersensitivity reactions (including anaphylactoid reactions), hallucinations, vivid dreams, granulomatous interstitial nephritis, sever narcosis and acute renal failure have been reported rarely during dihydrocodeine administration. Other adverse reactions observed with the ingredients in ENDACOF-DH Oral Liquid include, lassitude, nausea, giddiness, dryness of mouth, blurred vision, cardiac palpitations, flushing, increased irritability or excitement (especially in children).
DRUG ABUSE AND DEPENDENCE
This combination product is subject to the provisions of the Controlled Substance Act and has been placed in Schedule V. Dihydrocodeine can produce drug dependence of the codeine type and therefore has the potential of being abused. Psychological dependence, physical dependence, and tolerance may develop upon repeated administration of dihydrocodeine, and it should be prescribed and administered with the same degree of caution appropriate to the use of other oral opioid medications. Symptoms of dihydrocodeine withdrawal consist of irritability, restlessness, insomnia, diaphoresis, anxiety and palpitations.
OVERDOSAGE
An overdose of ENDACOF-DH Oral Liquid is a potentially lethal poly-drug overdose situation, and consultation with a regional Poison Control Center is recommended. A listing of the poison control centers can be found in standard references such as the Physician's Desk Reference®.
Signs and Symptoms
Symptoms of overdosage include pinpoint pupils, respiratory depression, extreme somnolence progressing to stupor, loss of consciousness, or coma, skeletal muscle, flaccidity, cold and clammy skin and other symptoms common with narcotic overdosage. Convulsions, cardiovascular collapse, and death may occur. A single case of acute rhabdomyolysis associated with an overdose of dihydrocodeine has been reported.
Recommended Treatment
Immediate treatment of an overdosage of ENDACOF-DH Oral Liquid includes support of cardiorespiratory function and measures to reduce drug absorption. Vomiting should be induced with syrup of ipecac, if the patient is alert and has adequate laryngeal reflexes. Oral activated charcoal should follow. The first dose should be accompanied by an appropriate cathartic. Gastric lavage may be necessary. Hypotension is usually hypovolemic and should be treated with fluids. Endotracheal intubation and artificial respiration may be necessary. The pure opioid antagonist naloxone or nalmefene is a specific antidote against respiratory depression that results from opioid overdose. Oipioid antagonists should not be given in the absence of clinically significant respiratory or circulatory depression secondary to opioid overdose. They should be administered cautiously to person who are known, or suspected to be, physically dependent on any opioid agonist including dihydrocodeine. IN such cases, an abrupt or complete reversal of opioid effects may precipitate an acute abstinence syndrome. The prescribing information for the specific opioid antagonist should be consulted for details of their proper use.
DOSAGE AND ADMINISTRATION1
Adults and children 12 years of age and older: 1 teaspoonful every 4 to 6 hours. Not to exceed 6 teaspoonfuls in a 24-hour period.
Children 6 to 12 years of age: 1/2 teaspoonful every 4 to 6 hours. Not to exceed 3 teaspoonfuls in a 24-hour period.
Not recommended for children under 6 years of age.
- 1
- In mild cases or in particularly sensitive patients, less frequent or reduced doses may be appropriate and adequate.
HOW SUPPLIED
A clear colored liquid with a cherry flavor supplied in 16 oz. bottles (NDC 68047-139-16).
Storage
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 15°-30°C (59°-86°F) [see USP Controlled Room Temperature.] Protect from freezing.
Dispense in a tight, light-resistant container as defined in the USP/NF with a child-resistant closure.
PRINCIPAL DISPLAY PANEL - 473 mL Bottle Label
NDC 68047-139-16
ENDACOF - DH
Liquid
ANTITUSSIVE / DECONGESTANT / ANTIHISTAMINE
SUGAR FREE ∙ ALCOHOL FREE ∙ DYE FREE
Each teaspoonful (5 mL) contains:
Phenylephrine HCl............... 7.5 mg
Brompheniramine Maleate.... 4 mg
Dihydrocodeine Bitartrate..... 3 mg
*(WARNING-May be habit forming)
Rx Only
LARKEN
LABORATORIES
16 fl. oz. (473 mL)
| ENDACOF
DH
dihydrocodeine bitartrate, brompheniramine maleate, and phenylephrine hydrochloride liquid |
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| Marketing Information | |||
| Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
| UNAPPROVED DRUG OTHER | 09/23/2009 | 11/30/2011 | |
| Labeler - Larken Laboratories, Inc. (791043719) |
| Registrant - Larken Laboratories, Inc. (791043719) |
Revised: 12/2009 Larken Laboratories, Inc.