Promethazine Contraindications and Precautions
- agranulocytosis
- bone marrow suppression
- breast-feeding
- coma
- jaundice
- neonates
- phenothiazine hypersensitivity
- Reye’s syndrome
- acute bronchospasm
- asthma
- bladder obstruction
- cardiac disease
- children
- chronic obstructive pulmonary disease (COPD)
- CNS depression
- contact lenses
- dehydration
- diabetes mellitus
- driving or operating machinery
- elderly
- ethanol intoxication
- GI obstruction
- glaucoma
- hepatic disease
- hepatic encephalopathy
- ileus
- infants
- pregnancy
- prostatic hypertrophy
- radiographic contrast administration
- respiratory depression
- seizure disorder
- sleep apnea
- urinary retention
Promethazine Contraindications and Precautions
Promethazine is contraindicated for use in patients with a known phenothiazine hypersensitivity. Cross-sensitivity may occur. This contraindication includes patients who have experienced agranulocytosis, blood dyscrasias, bone marrow suppression, or jaundice due to phenothiazine therapy. Promethazine is also contraindicated in patients who are in a coma.
Phenothiazine derivatives lower the seizure threshold through their effect on GABA; therefore, promethazine should be avoided, if possible, in patients with a seizure disorder or those receiving anticonvulsants. Additionally, extreme caution should be used when combining phenothiazine agents with other agents that can lower the seizure threshold, such as opioids or local anesthetics (see Drug Interactions).
The anticholinergic activity of H1-antagonists may result in thickened bronchial secretions in the respiratory tract thereby aggravating an acute asthmatic attack or chronic obstructive pulmonary disease (COPD). Although H1-antagonists should be avoided during an acute asthmatic attack or acute bronchospasm, these anticholinergic effects do not preclude the use of H1-antagonists in all asthmatic or COPD patients, particularly if the above respiratory symptom is not a primary component of the illness. Antihistamines (usually H2-antagonists with minimal anticholinergic activity) are frequently used in patients who have allergic rhinitis as a component of their asthma. However, the package labeling for promethazine states that antihistamines are contraindicated for use in the treatment of lower respiratory tract symptoms including asthma and should be avoided in patients with significant respiratory depression, including COPD and sleep apnea. Because promethazine exhibits a significant amount of anticholinergic activity, it should be avoided in those who have experienced a worsening in respiratory status due to H1-antagonist therapy.
Promethazine is extensively metabolized in the liver. The metabolism of promethazine may be reduced in the presence of hepatic disease, hepatic encephalopathy, or liver impairment. Those with significant hepatic disease receiving H1-antagonists should be monitored for liver function and side effects; dosage adjustments may be required in some patients. Promethazine should be avoided in pediatric patients whose signs or symptoms suggest the possibility of hepatic encephalopathy or other hepatic disease.
Promethazine is contraindicated for use in children < 2 years of age, infants and neonates due to the risk for fatal respiratory depression. Seizures and/or paradoxical CNS stimulation may also occur in this age group. Promethazine should be used cautiously in children > 2 years of age due to these reasons. If promethazine is used in children 2 years or older, the lowest possible effective dose should be given, and the concomitant use of other respiratory depressants should be avoided. There have been a number of cases of respiratory depression, sleep apnea, and SIDS in children receiving phenothiazine antihistamines at various weight-based dosages. The mechanism of this reaction is not yet known; therefore, promethazine should be used with extreme caution, if at all, in children with a family history of SIDS or sleep apnea. In general, antiemetics are not recommended for treatment of uncomplicated vomiting in children. Extrapyramidal symptoms that may occur in children receiving promethazine may be confused with signs of undiagnosed primary disease; thus the drug should be avoided in children whose signs or symptoms suggest the possibility of Reye’s syndrome, hepatic encephalopathy or other hepatic disease. In pediatric patients who are acutely ill associated with dehydration, there is an increased susceptibility to dystonic reactions with the use of promethazine.
Promethazine is classified under FDA pregnancy risk category C. H1-antagonists generally are not recommended for use in pregnancy, especially during the third trimester, because of a risk of seizure to the fetus. Because there are no adequate studies in pregnant women, promethazine should be considered during pregnancy only when the benefits of therapy outweigh the risks to the fetus. Promethazine administered to a pregnant woman within 2 weeks of delivery may inhibit platelet aggregation in the newborn. However, according to one manufacturer, limited data suggest that use of promethazine during labor and delivery does not have an appreciable effect on the duration of labor or delivery and does not increase the risk of need for intervention in the newborn. The effect on later growth and development of the newborn is unknown. Diagnostic pregnancy tests based on immunological reactions between HCG and anti-HCG may result in false-negative or false-positive interpretations.
In general, H1-antagonists are not recommended for use during breast-feeding because they can induce a paradoxical CNS stimulation in neonates or seizures in premature infants. Inhibition of lactation may also occur. Alternative methods of feeding should be used if promethazine therapy is necessary.
Clinical studies of promethazine did not include sufficient numbers of patients aged 65 years or over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in response between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Sedating drugs may cause confusion and over-sedation in the elderly; therefore, elderly patients should generally be started on low doses of promethazine and closely observed.
Promethazine should be avoided, if possible, in patients with open-angle or closed-angle glaucoma and an H1-antagonist with less anticholinergic effects should be substituted. An increase in intraocular pressure may occur from the anticholinergic actions of the drug, precipitating an acute attack of glaucoma. Elderly patients are more susceptible to the anticholinergic effects of promethazine, including possible precipitation of undiagnosed glaucoma. Other ocular effects resulting from the anticholinergic effects of promethazine include dry eyes or blurred vision. This may be of significance in the elderly and wearers of contact lenses.
Promethazine has substantial anticholinergic effects and a worsening of symptoms may be seen in patients with bladder obstruction, GI obstruction or ileus, benign prostatic hypertrophy, or urinary retention. These precautions are most significant when using antihistamines from the ethanolamine or phenothiazine group. The elderly are more susceptible to the anticholinergic effects of drugs since there is a decline in endogenous cholinergic activity that occurs with age.
The quinidine-like local anesthetic and anticholinergic effects of antihistamines are responsible for the adverse cardiac effects which have been observed including tachycardia, ECG changes, hypotension, and arrhythmias. Although these cardiovascular effects are uncommon, H1-antagonists should be used conservatively in patients with cardiac disease.
Phenothiazines can lower the seizure threshold. Because of a potential increased risk of seizures, phenothiazines should not be used during intrathecal radiographic contrast administration. Phenothiazines should be discontinued 48 hours before the myelography and should not be resumed until at least 24 hours after the procedure. Promethazine should not be used for the control of nausea and vomiting associated with these procedures.
Promethazine can cause drowsiness and CNS depression. Patients receiving promethazine should be advised to avoid driving or operating machinery or other hazardous tasks until the effects of the drug are known. Additionally, the combination of promethazine with other CNS depressants, such as ethanol, sedative/hypnotics, narcotics, other antihistamines, general anesthetics, or tricyclic antidepressants may augment CNS and/or respiratory depression. If such use cannot be avoided, a dose reduction in one or both agents may be required. Patients should avoid ethanol intoxication if taking promethazine.
Neuroleptic malignant syndrome (NMS) can occur in patients receiving phenothiazines (see Adverse Reactions). Severe cases have resulted in death 3 - 30 days after the onset of the syndrome. The phenothiazine should be immediately discontinued and appropriate supportive therapy initiated as soon as symptoms of NMS are discovered. Phenothiazines should be used extremely cautiously, if at all, in patients who have previously experienced neuroleptic malignant syndrome during phenothiazine treatment.
Phenothiazines have been reported to increase blood sugar. Since promethazine is a phenothiazine antihistamine, patients with diabetes mellitus should routinely monitor their blood glucose during concomitant phenothiazine therapy.
[ Last revised: 3/16/2005 12:42:00 PM ]
References
. Lindenmayer JP, Czobor P, Volavka J, et al. Changes in glucose and cholesterol levels in patients with schizophrenia treated with typical or atypical antipsychotics. Am J Psych 2003;160:290 - 96.
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