WARNINGS
Pseudodine™ C Cough Syrup should be used with considerable caution in patients with increased intraocular pressure (narrow angle glaucoma), stenosing peptic ulcer, pyloroduodenal obstruction, symptomatic prostatic hypertrophy, bladder neck obstruction, hypertension, diabetes mellitus, ischemic heart disease, and hyperthyroidism.
In the presence of head injury or other intracranial lesions, the respiratory depressant effects of codeine and other narcotics may be markedly enhanced, as well as their capacity for elevating cerebrospinal fluid pressure.
Narcotics also produce other CNS depressant effects, such as drowsiness, that may further obscure the clinical course of patients with head injuries.
Codeine or other narcotics may obscure signs on which to judge the diagnosis or clinical course of patients with acute abdominal conditions.
PRECAUTIONS
General
Pseudodine™ C Cough Syrup should be prescribed with caution for certain special-risk patients, such as the elderly or debilitated, and for those with severe impairment of renal or hepatic function, gallbladder disease or gallstones, respiratory impairment, cardiac arrhythmias, history of bronchial asthma, prostatic hypertrophy or urethral stricture, and in patients known to be taking other antitussive, antihistamine or decongestant medications. Patients' self-medication habits should be investigated to determine their use of such medications. Pseudodine™ C Cough Syrup is intended for short-term use only.
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 to 10% in Caucasians, 3% in African Americans, and 16 to 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. (See PRECAUTIONS-Nursing Mothers)
Information for Patients
- Patients should be warned about engaging in activities requiring mental alertness such as driving a car, operating dangerous machinery or hazardous appliances.
- Patients with a history of glaucoma, peptic ulcer, urinary retention or pregnancy should be cautioned before starting Pseudodine™ C Cough Syrup.
- Patients should be told not to take alcohol, sleeping pills, sedatives or tranquilizers while taking Pseudodine™ C Cough Syrup.
- Antihistamines may cause dizziness, drowsiness, dry mouth, blurred vision, weakness, nausea, headache or nervousness in some patients.
- Patients should be told to store this medicine in a tightly closed container in a dry, cool place away from heat or direct sunlight and out of the reach of children.
- Nursing Mothers - refer to following section titled "Nursing Mothers".
Pseudodine™ C Cough Syrup should not be used by persons intolerant to sympathomimetics used for the relief of nasal or sinus congestion. Such drugs include ephedrine, epinephrine, phenylephrine and phenylpropanolamine. Symptoms of intolerance include drowsiness, dizziness, weakness, difficulty in breathing, tenseness, muscle tremors or palpitations.
Codeine may be habit-forming when used over long periods or in high doses. Patients should take the drug only for as long, in the amounts, and as frequently as prescribed.
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).
Drug Interactions
Pseudodine™ C Cough Syrup may enhance the effects of:
- Monoamine oxidase (MAO) inhibitors;
- other narcotic analgesics, alcohol, general anesthetics, tranquilizers, sedative-hypnotics, surgical skeletal muscle relaxants, or other CNS depressants, by causing increased CNS depression.
Pseudodine™ C Cough Syrup may diminish the antihypertensive effects of guanethidine, bethanidine, methyldopa and reserpine.
Drug/Laboratory Test Interactions
Codeine
Narcotic administration may increase serum amylase levels.
Carcinogenesis, Mutagenesis, Impairment of Fertility
No adequate studies have been conducted in animals to determine whether the components of Pseudodine™ C Cough Syrup have a potential for carcinogenesis, mutagenesis or impairment of fertility.
Pregnancy
Teratogenic Effects
Pregnancy Category C
Animal reproduction studies have not been conducted with Pseudodine™ C Cough Syrup. It is also not known whether Pseudodine™ C Cough Syrup can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Pseudodine™ C Cough Syrup should be given to a pregnant woman only if clearly needed.
Teratology studies have been conducted with the three ingredients of Pseudodine™ C Cough Syrup. Pseudoephedrine studies were conducted in rats at doses up to 150 times the human dose; triprolidine was studied in rats and rabbits at doses up to 125 times the human dose, and codeine studies were conducted in rats and rabbits at doses up to 150 times the human dose. No evidence of teratogenic harm to the fetus was revealed in any of these studies. However, overt signs of toxicity were observed in the dams which received pseudoephedrine. This was reflected in reduced average weight and length and rate of skeletal ossification in their fetuses.
Nursing Mothers
The components of Pseudodine™ C Cough Syrup are excreted in breast milk in small amounts, but the significance of their effects on nursing infants is not known. Because of the potential for serious adverse reactions in nursing infants from maternal ingestion of Pseudodine™ C Cough Syrup, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
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 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 to 10% in Caucasians, 3% in African Americans, and 16 to 28% in North Africans, Ethiopians and Arabs. Data is not available for other ethnic groups.
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 excercised 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. (See PRECAUTIONS–General-Ultra-rapid Metabolizers of Codeine)
Pediatric Use
As in adults, the combination of an antihistamine, sympathomimetic amine and codeine can elicit either mild stimulation or mild sedation in pediatric patients. In pediatric patients particularly, the ingredients in this drug product in overdosage may produce hallucinations, convulsions and death. Symptoms of toxicity in pediatric patients may include fixed dilated pupils, flushed face, dry mouth, fever, excitation, hallucinations, ataxia, incoordination, athetosis, tonic clonic convulsions and postictal depression. (See CONTRAINDICATIONS and OVERDOSAGE sections.)
Use in Elderly (approximately 60 years or older)
The ingredients in Pseudodine™ C Cough Syrup are more likely to cause adverse reactions in elderly patients.
|
