Phenergan VC with Codeine Disease Interactions

Narcotic (opioid) analgesic agents increase smooth muscle tone in the gastrointestinal tract and decrease peristalsis, which can lead to elevated intraluminal pressure, spasm, and constipation following prolonged use. In patients with severe or acute inflammatory bowel disease, the decrease in colonic motility may induce toxic megacolon. Therapy with opioids should be administered cautiously in patients with gastrointestinal obstruction, constipation, inflammatory bowel disease, or recent gastrointestinal tract surgery. Gastrointestinal effects appear to be the most pronounced with morphine.

Narcotic (opioid) analgesic agents may prolong and/or worsen diarrhea associated with organisms that invade the intestinal mucosa, such as toxigenic Escherichia coli, Salmonella, Shigella, and pseudomembranous colitis due to broad-spectrum antibiotics. These agents decrease gastrointestinal motility, which may delay the excretion of infective gastroenteric organisms and/or their toxins. Other symptoms and complications such as fever, shedding of organisms, and extraintestinal illness may also be increased or prolonged. Therapy with opioids should be avoided or administered cautiously in patients with infectious diarrhea, particularly that due to pseudomembranous enterocolitis or enterotoxin-producing bacteria or if accompanied by high fever, pus, or blood in the stool.

The use of narcotic (opioid) analgesic agents is contraindicated in premature infants. These agents may cross the immature blood-brain barrier to a greater extent than in adults, resulting in disproportionate respiratory depression.

The use of opiate agonists is contraindicated in patients with acute alcohol intoxication exhibiting depressed vital signs. The central nervous system depressant effects of opiate agonists may be additive with those of alcohol. Severe respiratory depression and death may occur. Therapy with opiate agonists should be administered cautiously in patients who might be prone to acute alcohol intake.

Opiate agonists have the potential to cause dependence and abuse. Tolerance as well as physical and psychological dependence can develop after prolonged use. Abrupt cessation, reduction in dosage, or administration of an opiate antagonist such as naloxone may precipitate withdrawal symptoms. In patients who have developed tolerance to an opiate agonist, overdosage can still produce respiratory depression and death, and cross-tolerance usually will occur with other agents in the class. Addiction-prone individuals, such as those with a history of alcohol or substance abuse, should be under careful surveillance or medical supervision when treated with opiate agonists. It may be prudent to refrain from dispensing large quantities of medication to these patients. After prolonged use or if dependency is suspected, withdrawal of opiate therapy should be undertaken gradually using a dosage-tapering schedule.

Opiate agonists can induce vasodilation and significant hypotension, particularly when given in high dosages and/or by rapid intravenous administration. Opiate analgesics cause vasodilatation that may exacerbate hypotension and hypoperfusion and, therefore, are contraindicated in circulatory shock. At therapeutic analgesic dosages, ambulatory patients are more likely to experience dizziness and hypotension than patients who are confined to bed. However, orthostatic hypotension may occur in supine patients upon rising. Therapy with opiate agonists should be administered cautiously and initiated at reduced dosages in patients with hypovolemia, or a predisposition to hypotension. When given by intramuscular or subcutaneous administration, clinicians should also be aware that impaired perfusion in these patients may prevent complete absorption of the drug. With repeated injections, an excessive amount may be absorbed suddenly if normal circulation is reestablished.

The hypoventilation associated with administration of opiate agonists, particularly by the intravenous route, can induce cerebral hypoxia and vasodilatation with resultant increase in intracranial pressure. Opiate agonists should not be used in patients with suspected or known head injury or increased intracranial pressure. Also, clinicians treating such patients should be aware that opiate agonists may interfere with the evaluation of CNS function, especially with respect to consciousness levels, respiratory status, and pupillary changes.

Opiate agonists may produce significant central nervous system and respiratory depression of varying duration, particularly when given in high dosages and/or by rapid intravenous administration. Apnea may result from decreased respiratory drive as well as increased airway resistance, and rigidity of respiratory muscles may occur during rapid IV administration or when these agents are used in the induction of anesthesia. At therapeutic analgesic dosages, the respiratory effects are usually not clinically important except in patients with preexisting pulmonary impairment. Therapy with opiate agonists should be avoided or administered with extreme caution and initiated at reduced dosages in patients with severe CNS depression; sleep apnea; hypoxia, anoxia, or hypercapnia; upper airway obstruction; chronic pulmonary insufficiency; a limited ventilatory reserve; or other respiratory disorders. In the presence of excessive respiratory secretions, the use of opiate agonists may also be problematic because they decrease ciliary activity and reduce the cough reflex. Caution is also advised in patients who may be at increased risk for respiratory depression, such as comatose patients or those with head injury, intracranial lesions, or intracranial hypertension. Clinical monitoring of pulmonary function is recommended, and equipment for resuscitation should be immediately available if parenteral or neuraxial routes are used. Naloxone may be administered to reverse clinically significant respiratory depression, which may be prolonged depending on the opioid agent, cumulative dose, and route of administration.

Opioid analgesics are contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.

The use of phenothiazines is contraindicated in patients with acute alcohol intoxication exhibiting depressed vital signs. The central nervous system depressant effects of phenothiazines may be additive with those of alcohol. Severe respiratory depression and respiratory arrest may occur. Therapy with phenothiazines should be administered cautiously in patients who might be prone to acute alcohol intake.

Phenothiazines may cause hypotension (including orthostatic hypotension), reflex tachycardia, increased pulse rate, syncope, and dizziness, particularly after the first parenteral dose but rarely after the first oral dose. Low-potency agents such as chlorpromazine and thioridazine are more likely to induce these effects, which usually subside within the first couple of hours following administration. Tolerance to the hypotensive effects often develops after a few doses. Rarely, fatal cardiac arrest has occurred secondary to severe hypotension. Other reported adverse cardiovascular effects include edema, thrombosis, and ECG abnormalities such as PR and QT interval prolongation, diffuse T-wave flattening, and ST segment depression. Therapy with phenothiazines should be avoided or otherwise administered cautiously in patients with severe cardiovascular disease, pheochromocytoma, a predisposition to hypotension, or conditions that could be exacerbated by hypotension such as a history of myocardial infarction, angina, or ischemic stroke. Close monitoring of cardiovascular status, including ECG changes, is recommended at all dosages. If parenteral therapy is given, patients should be in a supine position during administration and for at least 30 to 60 minutes afterwards. Patients who experience orthostatic hypotension should be cautioned not to rise too abruptly. Occasionally, when severe, hypotension may require treatment with vasoconstrictive agents such as norepinephrine or phenylephrine. Epinephrine should not be used, however, since phenothiazines can reverse its vasopressor effects and cause a further lowering of blood pressure.

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.

The use of phenothiazines is contraindicated in patients with suspected or established subcortical brain damage, with or without hypothalamic involvement. Phenothiazines can interfere with thermoregulatory mechanisms, and a hyperthermic reaction with temperatures in excess of 104 F may occur in such patients, sometimes not until 14 to 16 hours after drug administration.

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.

Patients with Addison's disease may have increased risk of respiratory depression and prolonged CNS depression associated with the use of narcotic (opioid) analgesic agents. Conversely, these agents may cause or potentiate adrenal insufficiency. Therapy with opioids should be administered cautiously and initiated at reduced dosages in patients with adrenocortical insufficiency. Subsequent doses should be titrated based on individual response rather than a fixed dosing schedule.

Narcotic (opioid) analgesic agents are extensively metabolized by the liver, and several of them (e.g., codeine, hydrocodone, meperidine, methadone, morphine, propoxyphene) have active metabolites that are further converted to inactive substances. The serum concentrations of these agents and their metabolites may be increased and the half-lives prolonged in patients with impaired hepatic function. Therapy with opioids should be administered cautiously and initiated at reduced dosages in patients with liver disease. Subsequent doses should be titrated based on individual response rather than a fixed dosing schedule.

Although narcotic (opioid) analgesic agents are generally metabolized by the liver, renal impairment can alter the elimination of these agents and their metabolites (some of which are pharmacologically active), resulting in drug accumulation and increased risk of toxicity. Therapy with opioids should be administered cautiously and initiated at reduced dosages in patients with significantly impaired renal function. Subsequent doses should be titrated based on individual response rather than a fixed dosing schedule.

Narcotic (opioid) analgesic agents may increase the frequency of seizures in patients with seizure disorders, may increase the risk of seizures occurring in other clinical settings associated with seizures, and, at higher dosages, have been reported to induce seizures in patients without history of seizures. Patients with history of seizure disorders should be regularly evaluated for worsened seizure control during therapy. Prolonged meperidine use may increase the risk of toxicity (e.g., seizures) from the accumulation of the active metabolite (normeperidine).

Narcotic (opioid) analgesic agents may inhibit the urinary voiding reflex and increase the tone of the vesical sphincter in the bladder. Acute urinary retention requiring catheterization may occur, particularly in patients with prostatic hypertrophy or urethral stricture and in older adult patients. These agents may also decrease urine production via direct effects on the kidney and central stimulation of the release of vasopressin. Therapy with opioids should be administered cautiously in patients with or predisposed to urinary retention and/or oliguria. The effects on smooth muscle tone appear to be the most pronounced with morphine.

Opiate agonists have cholinergic activity. Large doses and/or rapid intravenous administration may produce bradycardia and arrhythmias via stimulation of medullary vagal nuclei. Therapy with opiate agonists should be administered cautiously in patients with a history of arrhythmias. Clinical monitoring of cardiovascular status is recommended during therapy.

Opioid agonists may cause spasm of the sphincter of Oddi, which may increase biliary tract pressure. Other opioid-induced effects may include a reduction in biliary and pancreatic secretions and transient elevations in serum amylase. Patients with biliary tract disease (including acute pancreatitis) should be regularly evaluated for worsening symptoms. Therapy with opioids should be administered cautiously in patients with biliary tract disease, gallbladder disease, or acute pancreatitis.

The chronic use of phenothiazines is associated with persistent elevations in prolactin levels. Based on in vitro data, approximately one-third of human breast cancers are thought to be prolactin-dependent. The clinical significance of this observation is unknown. Chronic administration of neuroleptic drugs has been associated with mammary tumorigenesis in rodent studies but not in human clinical or epidemiologic studies. Therapy with phenothiazines should be administered cautiously in patients with existing or suspected malignancy of the breast.

Phenothiazines may cause acute, dose-related dystonic reactions secondary to central dopaminergic blockade. These reactions are characterized by spastic contraction of discrete muscle groups and may include torticollis, opisthotonos, carpopedal spasm, trismus, difficulty swallowing, perioral spasms with protrusion of the tongue, and oculogyric crisis. Onset is usually within 24 to 96 hours following initiation of therapy or an increase in dosage. Risk factors include young age, male gender, use of high-potency agents (e.g., fluphenazine, perphenazine, trifluoperazine), high dosages, and IM administration. Therapy with phenothiazines should be administered cautiously in patients, particularly children, with hypocalcemia or severe dehydration, since these patients may be more susceptible to dystonic reactions. Most symptoms subside within a few hours and are almost always reversible within 24 to 48 hours following withdrawal of therapy. However, severe reactions such as laryngospasm may be life-threatening and require appropriate supportive therapy. Parenteral administration of an anticholinergic antiparkinsonian agent (e.g., benztropine, trihexyphenidyl) or diphenhydramine usually produces a prompt response and may be given orally for short-term maintenance to prevent recurrence of symptoms if phenothiazine therapy must be continued.

Phenothiazines may infrequently cause hematologic toxicity, including agranulocytosis, thrombocytopenia, eosinophilia, aplastic anemia, purpura, granulocytopenia, and hemolytic anemia. Mild leukopenia may occur frequently with large doses over prolonged periods but is generally reversible despite continued treatment. Therapy with phenothiazines should be administered cautiously, if at all, in patients with preexisting blood dyscrasias or bone marrow suppression. Complete blood counts should be obtained regularly, and patients should be instructed to immediately report any signs or symptoms suggestive of blood dyscrasia such as fever, sore throat, local infection, bleeding, pallor, dizziness, or jaundice. Most cases of agranulocytosis have occurred between the fourth and tenth weeks of therapy.

Phenothiazines are extensively metabolized by the liver and may accumulate in patients with hepatic impairment. In addition, the use of some phenothiazines has been associated with adverse hepatic effects including cholestatic jaundice and elevated liver enzymes, generally within the first few months of therapy. Cholestatic jaundice usually occurs between the second and fourth weeks of therapy in approximately 0.1% to 4% of all patients. Therapy with phenothiazines should be administered cautiously in patients with preexisting liver disease, liver enzyme abnormalities, or hepatitis. Liver function and urine bilirubin tests should be performed periodically during prolonged therapy, and patients should be instructed to immediately report any signs or symptoms suggestive of cholestatic jaundice such as upper abdominal pain, nausea, yellow skin, influenza-like symptoms, rash, and fever. Phenothiazine therapy should be discontinued, preferably permanently, if jaundice occurs and is attributable to the drug. Clinical recovery is usually observed within a few weeks following withdrawal of therapy, although histopathologic changes may persist for longer periods.

The central dopaminergic blocking effects of phenothiazines may precipitate or aggravate a potentially fatal symptom complex known as Neuroleptic Malignant Syndrome (NMS). NMS is observed most frequently when high-potency neuroleptic agents like haloperidol or fluphenazine are administered intramuscularly but may occur with any agent possessing neuroleptic activity given for any length of time. Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, altered mental status and autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac arrhythmias). Phenothiazine therapy should not be initiated in patients with active NMS and should be immediately discontinued if currently being administered in such patients. In patients with a history of NMS, introduction or reintroduction of phenothiazines should be carefully considered, since NMS may recur.

The use of phenothiazines is associated with pseudo-parkinsonian symptoms such as akinesia, bradykinesia, tremors, pill-rolling motion, cogwheel rigidity, and postural abnormalities including stooped posture and shuffling gait. The onset is usually 1 to 2 weeks following initiation of therapy or an increase in dosage. Propylamino derivatives such as chlorpromazine, promazine, and triflupromazine may be more likely to induce these effects. Therapy with phenothiazines should be administered cautiously in patients with Parkinson's disease or parkinsonian symptoms.

Phenothiazines and their metabolites are excreted by the kidney. There are very limited data concerning the use of phenothiazines in patients with renal disease. Therapy with phenothiazines should be administered cautiously in patients with significantly impaired renal function. The manufacturers recommend periodic renal function tests for all patients during prolonged therapy.

Phenothiazines can lower the seizure threshold and induce seizures, particularly when dosages are high or increased rapidly and during the initiation of therapy. Of the phenothiazines used in the treatment of psychosis, chlorpromazine appears to have the greatest epileptogenic potential, while fluphenazine and thioridazine have the least. Therapy with phenothiazines should be administered cautiously in patients with a history of seizures or other factors predisposing to seizures such as abnormal EEG, preexisting CNS pathology, or head trauma. Adequate anticonvulsant therapy should be maintained during administration of phenothiazines.

Phenothiazines may commonly precipitate symptoms of tardive dyskinesia (TD), a syndrome consisting of rhythmic involuntary movements variously involving the tongue, face, mouth, lips, jaw, and/or trunk and extremities, following chronic use of at least several months but often years. Elderly patients, particularly women, are most susceptible. Also, propylpiperazine derivatives like fluphenazine, perphenazine, prochlorperazine, and trifluoperazine may be more likely to induce this syndrome. Both the risk of developing TD and the likelihood that it will become irreversible increase with the duration and total cumulative dose of phenothiazine therapy administered. However, patients may infrequently develop symptoms after relatively brief treatment periods at low dosages. If TD occurs during phenothiazine therapy, prompt withdrawal of the offending agent or at least a lowering of the dosage should be considered. TD symptoms usually become more severe after drug discontinuation or a dosage reduction, but may gradually improve over months to years. In patients with preexisting drug-induced TD, initiating or increasing the dosage of phenothiazine therapy may temporarily mask the symptoms of TD but may eventually worsen the condition. The newer, atypical neuroleptic agents (e.g., risperidone, quetiapine, olanzapine) tend to be associated with a substantially reduced risk of inducing TD and are considered the drugs of choice in patients being treated for psychosis.

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.