hypotension associated with promethazine overdose. anticholinergics: concomitant use of other agents with anticholinergic properties should be undertaken with caution. monoamine oxidase inhibitors (maoi): drug interactions, nincluding an increased incidence of extrapyramidal effects, have been reported when some maoi and phenothiazines are used concomitantly. phenylephrine drug effect phenylephrine with prior administration of monoamine oxidase inhibitors (maoi). cardiac pressor response potentiated. may cause acute hypertensive crisis. phenylephrine with tricyclic antidepressants. pressor response increased. phenylephrine with ergot alkaloids. excessive rise in blood pressure. phenylephrine with bronchodilator sympathomimetic agents and with epinephrine or other sympathomimetics. tachycardia or other arrhythmias may occur. phenylephrine with atropine sulfate. reflex bradycardia blocked; pressor response enhanced. phenylephrine with prior administration of propranolol or other ß-adrenergic blockers. cardiostimulating effects blocked. phenylephrine with prior administration of phentolamine or other α-adrenergic blockers. pressor response decreased. phenylephrine with diet preparations, such as amphetamines or phenylpropanolamine. synergistic adrenergic response.

erating machinery. the impairment may be amplified by concomitant use of other central-nervous-system depressants such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore such agents should either be eliminated or given in reduced dosage in the presence of promethazine hcl (see precautions-information for patients and drug interactions ). respiratory depression: promethazine may lead to potentially fatal respiratory depression. use of promethazine in patients with compromised respiratory function (e.g., copd, sleep apnea) should be avoided. lower seizure threshold: promethazine may lower seizure threshold. it should be used with caution in persons with seizure disorders or in persons who are using concomitant medications, such as narcotics or local anesthetics, which may also affect seizure threshold. bone-marrow depression: promethazine should be used with caution in patients with bone-marrow depression. leukopenia and agranulocytosis have been reported, usually when promethazine hcl has been used in association with other known marrow-toxic agents. neuroleptic malignant syndrome: a potentially fatal symptom complex sometimes referred to as neuroleptic malignant syndrome (nms) has been reported in association with promethazine hcl alone or in combination with antipsychotic drugs. clinical manifestations of nms are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmias). the diagnostic evaluation of patients with this syndrome is complicated. in arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (eps). other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary central nervous system (cns) pathology. the management of nms should include 1) immediate discontinuation of promethazine hcl, antipsychotic drugs, if any, and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems for which specific treatments are available. there is no general agreement about specific pharmacological treatment regimens for uncomplicated nms. since recurrences of nms have been reported with phenothiazines, the reintroduction of promethazine hcl should be carefully considered. use in pediatric patients: promethazine products are contraindicated for use in pediatric patients less than two years of caution should be exercised when administering promethazine products to pediatric patients 2 years of age and older because of the potential for fatal respiratory depression. respiratory depression and apnea, sometimes associated with death, are strongly associated with promethazine products and are not directly related to individualized weight-based dosing, which might otherwise permit safe administration. concomitant administration of promethazine products with other respiratory depressants has an association with respiratory depression, and sometimes death, in pediatric patients. antiemetics are not recommended for treatment of uncomplicated vomiting in pediatric patients, and their use should be limited to prolonged vomiting of known etiology. the extrapyramidal symptoms which can occur secondary to promethazine hydrochloride administration may be confused with the cns signs of undiagnosed primary disease, e.g., encephalopathy or reye’s syndrome. the use of promethazine products should be avoided in pediatric patients whose signs and symptoms may suggest reye’s syndrome or other hepatic diseases . excessively large dosages of antihistamines, including promethazine hydrochloride, in pediatric patients may cause sudden death (see overdosage ). hallucinations and convulsions have occurred with therapeutic doses and overdoses of promethazine hydrochloride in pediatric patients. in pediatric patients who are acutely ill associated with dehydration, there is an increased susceptibility to dystonias with the use of promethazine hcl. other considerations: administration of promethazine has been associated with reported cholestatic jaundice. phenylephrine because phenylephrine is an adrenergic agent, it should be given with caution to patients with thyroid diseases, diabetes mellitus, and heart disease or those receiving tricyclic antidepressants. men with symptomatic, benign prostatic hypertrophy can experience urinary retention when given oral nasal decongestants. phenylephrine can cause a decrease in cardiac output, and extreme caution should be used when administering the drug parenterally or orally to patients with arteriosclerosis, to elderly individuals, and/or to patients with initially poor cerebral or coronary circulation. phenylephrine should be used with caution in patients taking diet preparations, such as amphetamines or phenylpropanolamine, because synergistic adrenergic effects could result in serious hypertensive response and possible stroke.

tal) and apnea (potentially fatal). (see warnings-promethazine ; respiratory depression .) other - angioneurotic edema. neuroleptic malignant syndrome (potentially fatal) has also been reported. (see warnings-promethazine ; neuroleptic malignant syndrome .) paradoxical reactions - hyperexcitability and abnormal movements have been reported in patients following a single administration of promethazine hcl. consideration should be given to the discontinuation of promethazine hcl and to the use of other drugs if these reactions occur. respiratory depression, nightmares, delirium, and agitated behavior have also been reported in some of these patients. phenylephrine nervous system – restlessness, anxiety, nervousness and dizziness. cardiovascular – hypertension (see “ warnings ”). other – precordial pain, respiratory distress, tremor, and weakness.

hypotension associated with promethazine overdose. anticholinergics: concomitant use of other agents with anticholinergic properties should be undertaken with caution. monoamine oxidase inhibitors (maoi): drug interactions, nincluding an increased incidence of extrapyramidal effects, have been reported when some maoi and phenothiazines are used concomitantly. phenylephrine drug effect phenylephrine with prior administration of monoamine oxidase inhibitors (maoi). cardiac pressor response potentiated. may cause acute hypertensive crisis. phenylephrine with tricyclic antidepressants. pressor response increased. phenylephrine with ergot alkaloids. excessive rise in blood pressure. phenylephrine with bronchodilator sympathomimetic agents and with epinephrine or other sympathomimetics. tachycardia or other arrhythmias may occur. phenylephrine with atropine sulfate. reflex bradycardia blocked; pressor response enhanced. phenylephrine with prior administration of propranolol or other ß-adrenergic blockers. cardiostimulating effects blocked. phenylephrine with prior administration of phentolamine or other α-adrenergic blockers. pressor response decreased. phenylephrine with diet preparations, such as amphetamines or phenylpropanolamine. synergistic adrenergic response.

rate overexposure to phenylephrine (3 mg/day) during the second half of pregnancy (22nd day of gestation to delivery) may contribute to perinatal wastage, prematurity, premature labor, and possibly fetal anomalies; when phenylephrine (3 mg/day) was given to rabbits during the first half of pregnancy (3rd day after mating for seven days), a significant number gave birth to litters of low birth weight. another study showed that phenylephrine was associated with anomalies of aortic arch and with ventricular septal defect in the chick embryo. promethazine and phenylephrine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. nonteratogenic effects – promethazine administered to a pregnant woman within two weeks of delivery may inhibit platelet aggregation in the newborn.

ct on β-receptors of the heart. phenylephrine has no effect on β-adrenergic receptors of the bronchi or peripheral blood vessels. a direct action at receptors accounts for the greater part of its effects, only a small part being due to its ability to release norepinephrine. therapeutic doses of phenylephrine mainly cause vasoconstriction. phenylephrine increases resistance and, to a lesser extent, decreases capacitance of blood vessels. total peripheral resistance is increased, resulting in increased systolic and diastolic blood pressure. pulmonary arterial pressure is usually increased, and renal blood flow is usually decreased. local vasoconstriction and hemostasis occur following topical application or infiltration of phenylephrine into tissues. the main effect of phenylephrine on the heart is bradycardia; it produces a positive inotropic effect on the myocardium in doses greater than those usually used therapeutically. rarely, the drug may increase the irritability of the heart, causing arrhythmias. cardiac output is decreased slightly. phenylephrine increases the work of the heart by increasing peripheral arterial resistance. phenylephrine has a mild central stimulant effect. following oral administration or topical application of phenylephrine to the mucosa, constriction of blood vessels in the nasal mucosa relieves nasal congestion associated with allergy or head colds. following oral administration, nasal decongestion may occur within 15 or 20 minutes and may persist for up to 4 hours. phenylephrine is irregularly absorbed from and readily metabolized in the gastrointestinal tract. phenylephrine is metabolized in the liver and intestine by monoamine oxidase. the metabolites and their route and rate of excretion have not been identified. the pharmacologic action of phenylephrine is terminated at least partially by uptake of the drug into tissues.

ntations was significantly reduced when high doses of the drug were used.