Phenylephrine/promethazine Disease Interactions

Phenothiazines are contraindicated in the presence of large amounts of central nervous system depressants such as alcohol. The risk of suicide and the danger of overdose may be increased in patients who use alcohol excessively. Phenothiazines should be used with caution in patients experiencing alcohol withdrawal.

The use of phenothiazines is contraindicated in comatose patients and patients with severe central nervous system depression. Phenothiazines may potentiate the CNS and respiratory depression in these patients.

Phenothiazines may cause hematologic toxicity. In patients with preexisting blood dyscrasias, bone marrow suppression, or a history of drug-induced leukopenia or neutropenia, phenothiazines should not be used or are contraindicated. Complete blood counts should be regularly monitored in patients with risk factors for blood dyscrasias. If white blood cell counts indicate cellular depression, discontinue treatment and institute appropriate therapy.

Phenothiazines may cause hypotension. Patients with pheochromocytoma, cerebral vascular or renal insufficiency, cardiovascular disease, or a severe cardiac reserve deficiency (e.g., mitral insufficiency) may be more prone to hypotensive reactions. Close monitoring is recommended during treatment if used in at-risk patients; some products may be contraindicated (e.g., thioridazine). Large doses and parenteral administration should be used cautiously, or avoided, in patients with impaired cardiovascular systems.

Therapy with phenothiazines should be administered cautiously or are contraindicated in patients with preexisting liver disease or with a history of jaundice due to phenothiazine hypersensitivity. Patients with a history of hepatic encephalopathy due to cirrhosis may have increased sensitivity to the central nervous system effects of some phenothiazines (e.g., chlorpromazine). Treatment should be discontinued if jaundice occurs.

Promethazine has weak central antidopaminergic activity. While its use is rarely associated with adverse effects secondary to dopaminergic blockade, large doses have produced extrapyramidal reactions. During chronic administration and/or high-dose therapy, the usual contraindications, warnings and precautions applicable to phenothiazines should be observed with promethazine.

Promethazine is contraindicated for use in the treatment of lower respiratory tract symptoms including asthma. Furthermore, promethazine tablets may lead to potentially fatal respiratory depression, and its use should be avoided in patients with compromised respiratory function such as patients with COPD, and sleep apnea.

Sympathomimetic agents may cause adverse cardiovascular effects, particularly when used in high dosages and/or in susceptible patients. In cardiac tissues, these agents may produce positive chronotropic and inotropic effects via stimulation of beta- 1 adrenergic receptors. Cardiac output, oxygen consumption, and the work of the heart may be increased. In the peripheral vasculature, vasoconstriction may occur via stimulation of alpha-1 adrenergic receptors. Palpitations, tachycardia, arrhythmia, hypertension, reflex bradycardia, coronary occlusion, cerebral vasculitis, myocardial infarction, cardiac arrest, and death have been reported. Some of these agents, particularly ephedra alkaloids (ephedrine, ma huang, phenylpropanolamine), may also predispose patients to hemorrhagic and ischemic stroke. Therapy with sympathomimetic agents should generally be avoided or administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism, or underlying cardiovascular or cerebrovascular disorders. These agents should not be used in patients with severe coronary artery disease or severe/uncontrolled hypertension.

Antihistamines often have anticholinergic activity, to which elderly patients are particularly sensitive. Therapy with antihistamines should be administered cautiously, if at all, in patients with preexisting conditions that are likely to be exacerbated by anticholinergic activity, such as urinary retention or obstruction; angle-closure glaucoma, untreated intraocular hypertension, or uncontrolled primary open-angle glaucoma; and gastrointestinal obstructive disorders. Conventional, first-generation antihistamines such as the ethanolamines (bromodiphenhydramine, carbinoxamine, clemastine, dimenhydrinate, diphenhydramine, doxylamine, phenyltoloxamine) tend to exhibit substantial anticholinergic effects. In contrast, the newer, relatively nonsedating antihistamines (e.g., cetirizine, fexofenadine, loratadine) reportedly have low to minimal anticholinergic activity at normally recommended dosages and may be appropriate alternatives.

It has been suggested that the anticholinergic effect of antihistamines may reduce the volume and cause thickening of bronchial secretions, resulting in obstruction of respiratory tract. Some manufacturers and clinicians recommend that therapy with antihistamines be administered cautiously in patients with asthma or chronic obstructive pulmonary disease.

The chronic use of phenothiazines is associated with persistent elevations in prolactin levels. The clinical significance in patients with a history of breast cancer is unknown and should be considered prior to therapy; approximately one-third of human breast cancers are thought to be prolactin-dependent. Chronic administration of neuroleptic drugs has been associated with mammary tumorigenesis in animal studies; however, evidence is inconclusive in humans.

Therapy with phenothiazines may precipitate or aggravate a potentially fatal symptom complex known as neuroleptic malignant syndrome (NMS). Treatment should not be initiated in patients with active NMS, and should be immediately discontinued if currently administered in such patients. In patients with a history of NMS, introduction or reintroduction of phenothiazines should be carefully considered, since NMS may recur.

Phenothiazines can lower the seizure threshold. Caution is recommended during administration in patients with a history of convulsive disorders or EEG abnormalities. Anticonvulsant therapy should be maintained or adequately adjusted during phenothiazine treatment.

Promethazine has weak central antidopaminergic activity. While its use is rarely associated with adverse effects secondary to dopaminergic blockade, large doses have produced extrapyramidal reactions. During chronic administration and/or high-dose therapy, the usual contraindications, warnings and precautions applicable to phenothiazines should be observed with promethazine.

Sympathomimetic agents may cause or worsen urinary difficulty in patients with prostate enlargement due to smooth muscle contraction in the bladder neck via stimulation of alpha-1 adrenergic receptors. Therapy with sympathomimetic agents should be administered cautiously in patients with hypertrophy or neoplasm of the prostate.

Sympathomimetic agents may cause increases in blood glucose concentrations. These effects are usually transient and slight but may be significant with dosages higher than those normally recommended. Therapy with sympathomimetic agents should be administered cautiously in patients with diabetes mellitus. Closer monitoring of blood glucose concentrations may be appropriate.

Sympathomimetic agents can induce transient mydriasis via stimulation of alpha-1 adrenergic receptors. In patients with anatomically narrow angles or narrow-angle glaucoma, pupillary dilation can provoke an acute attack. In patients with other forms of glaucoma, mydriasis may occasionally increase intraocular pressure. Therapy with sympathomimetic agents should be administered cautiously in patients with or predisposed to glaucoma, particularly narrow-angle glaucoma.