TL-HIST CM Liquid

Codeine is contraindicated in patients with a known hypersensitivity to the drug.

Antihistamines and codeine are both contraindicated for use in the treatment of lower respiratory tract symptoms, including asthma. Antihistamines and anticholinergics are contraindicated in patients with narrow angle glaucoma, urinary retention, peptic ulcer and during an asthma attack. Contraindicated in breast-feeding mothers.

General

Before prescribing medication to suppress or modify cough, it is important that the underlying cause of cough is identified, that modification of cough does not increase the risk of clinical or physiological complications, and that appropriate therapy for the primary disease is instituted.

Narcotic analgesics, including codeine, should be administered with caution and the initial dose reduced in patients with acute abdominal conditions, convulsive disorders, significant hepatic or renal impairment, fever, hypothyroidism, Addison's disease, ulcerative colitis, prostatic hypertrophy, in patients with recent gastrointestinal or urinary tract surgery, and in the very young or elderly or debilitated patients.

Ultra-rapid Metabolizers of Codeine

Some individuals may be ultra-rapid metabolizers due to a specific CYP2D6*2×2 genotype. These individuals convert codeine into its active metabolite, morphine, more rapidly and completely than other people. This rapid conversion results in higher than expected serum morphine levels. Even at labeled dosage regiments, individuals who are ultra-rapid metabolizers may experience overdose symptoms such as extreme sleepiness, confusion or shallow breathing.

The prevalence of this CYP2D6 phenotype varies widely and has been estimated at 0.5 to 1% in Chinese and Japanese, 0.5 to 1% in Hispanics, 1-10% in Caucasians, 3% in African Americans, and 16-28% in North Africans, Ethiopians and Arabs. Data is not available for other ethnic groups. When physicians prescribe codeine-containing drugs, they should choose the lowest effective dose for the shortest period of time and should inform their patients about these risks and the signs of morphine overdose.

Drug/Laboratory Test Interactions

In patients receiving MAO inhibitors, an initial small test dose is advisable to allow observation of any excessive narcotic effects or MAOI interaction.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No data are available on the long-term potential for carcinogenesis, mutagenesis, or impairment of fertility in animals or humans.

Pregnancy

A study in rats and rabbits reported no teratogenic effect of codeine administered during the period of organogenesis in doses ranging from 5 to 120 mg/kg. In the rat, doses at the 120-mg/kg level, in the toxic range for the adult animal were associated with an increase in embryo resorption at the time of implantation. In another study a single 100-mg/kg dose of codeine administered to pregnant mice reportedly resulted in delayed ossification in the offspring. There are no studies in humans, and the significance of these findings to humans, if any, is not known. Do not use during third trimester.

Labor and Delivery

Narcotic analgesics cross the placental barrier. The closer to delivery and the larger the dose used, the greater the possibility of respiratory depression in the newborn. Narcotic analgesics should be avoided during labor if delivery of a premature infant is anticipated. If the mother has received narcotic analgesics during labor, newborn infants should be observed closely for signs of respiratory depression. Resuscitation may be required.

Nursing Mothers

Codeine is secreted into human milk. In women with normal codeine metabolism (normal CYP2D6 activity), the amount of codeine secreted into human milk is low and dose-dependent. Despite the common use of codeine products to manage postpartum pain, reports of adverse events in infants are rare. However, some women are ultra-rapid metabolizers of codeine. These women achieve higher-than-expected serum levels of codeine's active metabolite, morphine, leading to higher-than-expected levels of morphine in breast milk and potentially dangerously high serum morphine levels in their breastfed infants. Therefore, maternal use of codeine can potentially lead to serious adverse reactions, including death, in nursing infants.

The risk of infant exposure to codeine and morphine through breast milk should be weighed against the benefits of breastfeeding for both the mother and baby. Caution should be exercised when codeine is administered to a nursing woman. If a codeine-containing product is selected, the lowest dose should be prescribed for the shortest period of time to achieve the desired clinical effect. Mothers using codeine should be informed about when to seek immediate medical care and how to identify the signs and symptoms of neonatal toxicity, such as drowsiness or sedation, difficulty breastfeeding, breathing difficulties, and decreased tone, in their baby. Nursing mothers who are ultra-rapid metabolizers may also experience overdose symptoms such as extreme sleepiness, confusion or shallow breathing. Prescribers should closely monitor mother-infant pairs and notify treating pediatricians about the use of codeine during breastfeeding.

Information for Patients

Codeine may cause marked drowsiness or may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a vehicle or operating machinery. Ambulatory patients should be told to avoid engaging in such activities until it is known that they do not become drowsy or dizzy from codeine therapy.

The concomitant use of alcohol or other central nervous system depressants, including narcotic analgesics, sedatives, hypnotics, and tranquilizers, may have an additive effect and should be avoided or their dosage reduced.

Patients should be advised to report any involuntary muscle movements. Avoid prolonged exposure to the sun. Codeine, like other narcotic analgesics, may produce orthostatic hypotension in some ambulatory patients. Patients should be cautioned accordingly. Caution patients that some people have a variation in a liver enzyme and change codeine into morphine more rapidly and completely than other people. These people are ultra-rapid metabolizers and are more likely to have higher-than-normal levels of morphine in their blood after taking codeine which can result in overdose symptoms such as extreme sleepiness, confusion, or shallow breathing. In most cases, it is unknown if someone is an ultra-rapid codeine metabolizer. Nursing mothers taking codeine can also have higher morphine levels in their breast milk if they are ultra-rapid metabolizers. These higher levels of morphine in breast milk may lead to life-threatening or fatal side effects in nursing babies. Instruct nursing mothers to watch for signs of morphine toxicity in their infants including increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness. Instruct nursing mothers to talk to the baby's doctor immediately if they notice these signs and, if they cannot reach the doctor right away, to take the baby to an emergency room or call 911 (or local emergency services).

Caution patient using Chlorpheniramine that each product has specific dosing instructions and to read package label before using and not to exceed dose or frequency of administration instructions. Advise patient to take each dose without regard to meals, but to take with food if stomach upset occurs. Advise patient or caregiver using oral syrup to measure and administer prescribed dose using dosing syringe, dosing spoon, or dosing cup. Advise patient that if a dose is missed, to take it as soon as possible unless it is nearing time for the next scheduled dose. If it is nearing time for next scheduled dose, advise patient to skip the missed dose and take the next dose at the regularly scheduled time. Caution patient not to double the dose to catch up. Advise patient that if allergy symptoms are not controlled, not to increase the dose of medication or frequency of use but to inform health care provider. Caution patient that larger doses or more frequent dosing does not increase efficacy and may cause excessive drowsiness or other adverse reactions. Instruct patient to stop taking drug and immediately report any of these symptoms to health care provider: persistent dizziness; excessive drowsiness; severe dry mouth, nose, or throat; flushing; unexplained shortness of breath or difficulty breathing; unusual tiredness or weakness; sore throat, fever, or other signs of infection; bleeding or unusual bruising; fast or irregular heartbeat; excitability, confusion, or changes in thinking or behavior; chest tightness; difficulty with urination. Advise patient medication may cause drowsiness or dizziness and not to drive or perform other activities requiring mental alertness until tolerance is determined. Advise patient to take sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs. Caution patient alcohol and other CNS depressants (e.g., sedatives) will have additional sedative effects if taken with Chlorpheniramine. Caution patient not to take any other OTC antihistamines while taking this medication unless advised by health care provider. Caution patient that medication may cause sensitivity to sunlight and to avoid excessive exposure to the sun or UV light (e.g., tanning booths) and to wear protective clothing and use sunscreens until tolerance is determined. If patient is to have allergy skin testing, advise patient not to take the medication for at least 4 days before the skin testing.

Use in the Elderly

Use with caution, usually starting at the low end of the dosage range because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.

Serious overdose with codeine 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. The triad of coma, pinpoint pupils, and respiratory depression is strongly suggestive of opiate poisoning. In severe overdosage, particularly by the intravenous route, apnea, circulatory collapse, cardiac arrest, and death may occur. It is difficult to determine what constitutes a standard toxic or lethal dose. However, the lethal oral dose of codeine in an adult is reported to be in the range of 0.5 to 1 gram. Infants and children are believed to be relatively more sensitive to opiates on a body-weight basis. Elderly patients are also comparatively intolerant to opiates. Treatment of overdosage with codeine is essentially symptomatic and supportive. Only in cases of extreme overdosage or individual sensitivity do vital signs including respiration, pulse, blood pressure, temperature, and EKG need to be monitored. Activated charcoal orally or by lavage may be given, or sodium or magnesium sulfate orally as a cathartic. Attention should be given to the reestablishment of adequate respiratory exchange through provision of a patient airway and institution of assisted or controlled ventilation. The narcotic antagonist, naloxone hydrochloride, may be administered when significant respiratory depression occurs with codeine; Severe hypotension usually responds to the administration of norepinephrine or Phenylephrine. EPINEPHRINE SHOULD NOT BE USED, since its use in a patient with partial adrenergic blockade may further lower the blood pressure. Limited experience with dialysis indicates that it is not helpful. Overdosage with Chlorpheniramine may cause hallucinations, convulsions, and death. Antihistamines may diminish mental alertness. In young children, they may produce paradoxical excitation.

TL-HIST CM Liquid is a clear, cotton candy flavored liquid which contains 10 mg Codeine Phosphate and 2 mg Chlorpheniramine Maleate, available in 16 fl oz (473 mL) bottles.

NDC 13811-070-16

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.

RX Only

Dispense in a tight, light-resistant container as defined in USP/NF with a child-resistant closure.

Store at controlled room temperature 15°-30°C (59°-86°F).

Manufactured for:
Trigen Laboratories, Inc.
Sayreville, NJ 08872

Rev. 12/09

NDC 13811-070-16

TL-HIST CM
Liquid

Cough Suppressant • Antihistamine

Each 5 mL (1 teaspoonful) of
cotton candy flavored liquid
for oral administration contains:

TRIGEN
LABORATORIES

16 fl oz (473 mL)

Applies to chlorpheniramine / codeine: oral liquid, oral suspension, oral suspension extended release, oral tablet

Cardiovascular

Codeine or Chlorpheniramine:
Frequency not reported: Fast, or slow heartbeat, hypertension, hypotension, orthostatic hypotension, palpitations, shock-like state, syncope[Ref]

Nervous system

Codeine or Chlorpheniramine:
Frequency not reported: Weakness, dizziness, drowsiness, sedation, headache, facial dyskinesia, lightheadedness, somnolence, dyskinesia, tremor[Ref]

Gastrointestinal

Codeine or Chlorpheniramine:
Frequency not reported: Nausea, vomiting, constipation, abdominal distension, abdominal pain, acute pancreatitis, dry mouth, dyspepsia, epigastric distress, diarrhea, gastro-esophageal reflux, gastrointestinal hypomotility[Ref]

Respiratory

Codeine:
Frequency not reported: Respiratory depression, dryness of the pharynx and respiratory passages, laryngismus, atelectasis, wheezing, troubled breathing, hiccups[Ref]

Endocrine

Codeine or Chlorpheniramine:
Frequency not reported: Decreased lactation, early menses, gynecomastia, increased libido, pheochromocytoma stimulation[Ref]

Dermatologic

Codeine or Chlorpheniramine:
Frequency not reported: Redness or flushing of face, skin rash, pruritus, erythema, urticaria, excessive perspiration, dermatitis[Ref]

Hypersensitivity

Codeine or Chlorpheniramine:
Frequency not reported: Allergic laryngospasm, nasal stuffiness, bronchospastic allergic reaction, hives, itching, swelling of face[Ref]

Ocular

Codeine or Chlorpheniramine:
Frequency not reported: Blurred vision, diplopia, visual disturbances, hypermetropia, lacrimation increased, mydriasis, photophobia[Ref]

General

The more commonly reported adverse effects have included nausea, vomiting, constipation, blurred vision, confusion, dizziness, depression, drowsiness, headache, lightheadedness, insomnia, irritability, and tremor.[Ref]

Other

Codeine or Chlorpheniramine:
Frequency not reported: Asthenia, feeling of relaxation, unusual tiredness, labyrinthitis, tinnitus, vertigo[Ref]

Metabolic

Codeine or Chlorpheniramine:
Frequency not reported: Changes in glucose utilization, glycosuria, hypoglycemia, increased appetite, loss of appetite[Ref]

Psychiatric

Codeine:
Frequency not reported: Drug dependence, confusion, depression, euphoria, false sense of well-being, excitability, nervousness, agitation, restlessness, insomnia, irritability[Ref]

Some side effects of TL-Hist CM may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.