Thiothixene is an antipsychotic drug that is structurally similar to trifluoperazine and shares some of the pharmacological properties of the high-potency antipsychotics. It is used in the treatment of psychotic disorders and schizophrenia. Five milligrams of thiothixene is equivalent to 100 mg of chlorpromazine, the prototype antipsychotic. Thiothixene was approved by the FDA in 1967.
On June 16, 2008, the FDA announced that it is requesting manufacturers of conventional antipsychotics to add a boxed warning to their product labeling regarding an increased risk of death in elderly patients with dementia receiving these drugs for behavioral problems. This warning was first required in the product labeling of atypical antipsychotics in 2005, although recent data indicate an increased risk among both conventional and atypical antipsychotics (see Contraindications).
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-May administer oral dosage forms with or without food. If stomach upset or nausea occur, take with food.
Oral Solid Formulations
Capsules:
-Administer orally as prescribed.
Thiothixene is structurally similar to piperazine phenothiazines (e.g., fluphenazine, perphenazine), which frequently cause extrapyramidal symptoms (EPS). Extrapyramidal symptoms appear to be the result of D2-receptor blockade. These symptoms occur with greater severity and frequency during high-dose therapy, and with use of high potency antipsychotics such as thiothixene. Extrapyramidal symptoms are categorized as dystonic reaction, akathisia, and pseudoparkinsonism. Dystonic reaction is a potential effect of all antipsychotics, and may occur in susceptible individuals during the first few days of treatment. This effect is observed more commonly in males, younger age groups, and with high potency antipsychotics. Dystonic reactions may manifest as torticollis with or without throat tightness, difficulty swallowing or breathing, oculogyric crisis, trismus, or protrusion of the tongue. Pseudoparkinsonism may occur 1-2 weeks after initiation of antipsychotic therapy and is more common in elderly patients. Akathisia may develop several days to weeks into therapy and may respond to dosage reduction or concomitant administration of a benzodiazepine (usually lorazepam) or a beta-blocker (e.g., propranolol, metoprolol). In some patients, an alternate antipsychotic may be necessary. Extrapyramidal symptoms (e.g., hypertonia, tremor, hyperreflexia) have been reported after delivery in neonates exposed to antipsychotics during the third trimester. These effects have varied in severity ranging from self-limited to requiring intensive care unit stays and prolonged hospitalization.
A potentially fatal symptom complex referred to as neuroleptic malignant syndrome (NMS) has occurred in association with administration of antipsychotics, including thiothixene. NMS is characterized by hyperpyrexia, severe extrapyramidal dysfunction, alterations in consciousness, altered mental status, and autonomic instability (tachycardia, low blood pressure or hypertension, diaphoresis). Increased serum creatine phosphokinase (CPK), acute renal failure, and increased leukocyte count may also occur. The cause of NMS is not completely understood; however, dopamine receptor blockade is one of the mechanisms by which NMS is thought to occur. A primary risk factor for developing NMS appears to be the initiation or increase in dose of an antipsychotic. High potency and depot antipsychotics carry the greatest risk. Environmental risk factors include conditions that inhibit heat dissipation such as an elevated ambient room temperature, prolonged heat exposure, the use of patient restraints, or dehydration. NMS occurs more frequently in young adults, which is most likely the result of age of first exposure rather than an age-related risk. NMS occurs more frequently in men, which is thought to be related to the higher likelihood of male versus female exposure to the causative agent. Risk factors for recurrent NMS include a personal history of NMS, increasing age, and certain medical co-morbidities (e.g., electrolyte imbalances, dehydration). Thiothixene should be immediately discontinued and appropriate supportive therapy initiated as soon as symptoms of NMS are discovered.
Tardive dyskinesia (TD) is characterized by involuntary movements of the perioral region (tongue, mouth, jaw, eyelids, or face) or choreoathetoid movements in the extremities. It can develop during long-term therapy or following discontinuation of antipsychotic therapy, and it is observed more frequently in elderly women. The incidence of TD may be higher in patients with bipolar disorder than with schizophrenia. Some cases can be irreversible. While contradictory evidence exists, it has been suggested that the likelihood of developing TD increases with prolonged treatment and cumulative doses. Although this complication often occurs following prolonged treatment or with administration of high dosages, it also has been reported to occur after short periods of time and with low dosages. If signs or symptoms of TD develop, the antipsychotic should be re-evaluated and possibly discontinued. Routine monitoring (at 3- to 6-month intervals) of movement disorders is considered the standard practice when using thiothixene or other antipsychotics.
Thiothixene has a side effect profile similar to the structurally related piperazine phenothiazines (e.g., fluphenazine, perphenazine). Drowsiness can occur during initial treatment; however, drowsiness is less likely with high potency antipsychotics such as thiothixene than low potency antipsychotics such as chlorpromazine. Tolerance usually develops with continued therapy. Dizziness may occur as a result of orthostasis; however, high potency antipsychotics are less likely than low potency antipsychotics to cause orthostatic effects. Other CNS effects reported during thiothixene therapy include restlessness, agitation, insomnia, weakness, fatigue, and exacerbation of psychotic symptoms such as hallucinations. Seizures can occur and are of special significance in patients with pre-existing seizure disorders or EEG abnormalities. Phenothiazines have been associated with cerebral edema and cerebrospinal fluid abnormalities; these effects have the potential to occur during thiothixene administration. Because drowsiness is a possible side effect of thiothixene, patients should be advised to use caution when driving, operating machinery, or performing other tasks that require mental alertness until they know how the drug affects them.
General adverse reactions that have been reported during thiothixene administration include nasal congestion (autonomic effect) and peripheral edema.
Clinical trial data and post-marketing reports indicate that leukopenia, neutropenia, and agranulocytosis have occurred during the use of antipsychotic agents. Leukopenia and leukocytosis (usually transient) can occur occasionally during treatment with thiothixene. Hematologic abnormalities that have been associated with other antipsychotics include agranulocytosis, eosinophilia, hemolytic anemia, aplastic anemia, thrombocytopenia, thrombocytopenic purpura, and pancytopenia. Patients with a history of drug-induced leukopenia or neutropenia or history of clinically significant low white blood cell (WBC) count should have their complete blood count (CBC) monitored regularly during the first few months of therapy, and thiothixene should be discontinued in such patients at the first sign of a decline in WBC in the absence of an identifiable cause. Patients with neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Thiothixene should be discontinued in patients who develop severe neutropenia as noted by an absolute neutrophil count (ANC) less than 1000/mm3).
Similar to many other antipsychotics, hyperhidrosis has been reported during thiothixene therapy. Hypersensitivity reactions, including rash (unspecified), pruritus, urticaria, photosensitivity, and anaphylaxis (rare) have also been reported. Thiothixene is structurally similar to the phenothiazines which, after prolonged therapy, can cause skin hyperpigmentation. Hyperpigmentation generally is restricted to areas of the body exposed to sunlight. Photosensitivity can result, and patients should be warned either to keep out of the sun or to use effective sunscreens on exposed areas of the body. Withdrawal of the drug can reverse the effects. Although not reported with thiothixene, contact dermatitis has been observed in nursing personnel after direct contact with liquid dosage forms of other antipsychotics.
Blurred vision has occurred infrequently during thiothixene therapy, and is typically the result of the anticholinergic effects of antipsychotics. Pigmentary retinopathy and lenticular pigmentation have been reported in a small number of patients receiving thiothixene. Wearing protective dark glasses can reduce the possibility of pigmentary retinopathy. Phenothiazines, which are structurally related to thiothixene, have been associated with pigmentary retinopathy, miosis, mydriasis, and deposition of fine particles in the lens and cornea, which can lead to corneal opacification and visual impairment. Because of the potential for serious adverse ocular effects, symptoms of blurred vision, difficulty with nighttime vision, or defective color vision should be investigated promptly during thiothixene administration.
Adverse gastrointestinal (GI) effects that have been reported during treatment with thiothixene include xerostomia, nausea, vomiting, diarrhea, hypersalivation, anorexia, appetite stimulation, weight gain, elevated hepatic enzymes (usually transient increases in transaminases, alkaline phosphatase), and constipation. Some GI effects, such as xerostomia and constipation, are generally due to the anticholinergic effects of antipsychotics. Weight gain is considered a class effect of antipsychotics and can be significant. In some cases, weight gain may be associated with antipsychotic-induced increases in prolactin levels or appetite stimulation. Although not reported with thiothixene, cholestasis and jaundice attributable to the structurally related phenothiazine antipsychotics have occurred. Adynamic ileus has also been reported during phenothiazine administration. Dysphagia, with possible aspiration of gastric contents, can occur during antipsychotic use. This adverse effect may increase the incidence of aspiration pneumonia in certain patient populations, such as elderly patients with advanced Alzheimer's disease or other dementia. Patients with dysphagia or who are at risk for aspiration should be closely monitored while receiving thiothixene.
Blockade of alpha-1 adrenergic receptors by antipsychotics may produce cardiovascular effects such as hypotension, orthostatic hypotension, sinus tachycardia, and changes in ECG patterns; however, these effects are less likely to occur with high potency antipsychotics such as thiothixene than low potency antipsychotics such as chlorpromazine. Cardiac effects that have been reported during treatment with thiothixene include sinus tachycardia, hypotension, lightheadedness, syncope, and ECG changes. Patients who are at risk for orthostatic hypotension should be counseled on measures to prevent orthostasis, such as sitting on the edge of the bed for several minutes prior to standing in the morning, or rising slowly from a seated position. Thiothixene is structurally related to piperazine phenothiazines (e.g., fluphenazine, perphenazine), which have a possible risk for QT prolongation and/or torsade de pointes (TdP). Sudden deaths have occasionally been reported in patients who have received certain phenothiazine derivatives. In some cases, the cause of death was apparently cardiac arrest or asphyxia due to failure of the cough reflex. In others, the cause could not be determined nor could it be established that death was due to phenothiazine administration.
Hyperprolactinemia has been reported during thiothixene administration. Central dopamine blockade by antipsychotics can lead to elevations in prolactin levels, which can affect reproductive or sexual functioning. Such prolactin-induced effects include amenorrhea or other menstrual irregularity, breast enlargement or mastalgia, galactorrhea, gynecomastia, libido decrease, impotence (erectile dysfunction), infertility, or ejaculation dysfunction (e.g., ejaculatory failure). Galactorrhea, menstrual irregularity, moderate breast enlargement, and amenorrhea have been reported in a small percentage of female patients receiving thiothixene. Impotence has been reported infrequently in male patients receiving the drug. Chronic hyperprolactinemia may result in loss of bone density (osteopenia) in both males and females. Evidence is limited as to the possible connection between increased serum prolactin and breast cancer. False positive pregnancy tests have been reported during use of phenothiazines, which are structurally related to thiothixene.
Thiothixene is structurally related to piperazine phenothiazines (e.g., fluphenazine, perphenazine), and a similar side effect profile can be expected. Hyperglycemia, hypoglycemia, and glycosuria have been reported during phenothiazine derivative administration, although the frequencies are unknown. Hyperglycemia and diabetes mellitus, in some cases extreme and associated with diabetic ketoacidosis, hyperosmolar coma, or death, have been reported in patients treated with antipsychotics. The possibility of impaired glucose tolerance should be considered in patients receiving thiothixene who develop symptoms of hyperglycemia or diabetes, such as excess thirst, polyuria, polyphagia, and weakness. Discontinuation of thiothixene therapy should be considered if symptoms are severe.
Antipsychotics, including thiothixene, are not FDA approved for the treatment of dementia-related psychosis in geriatric patients. In April 2005, the FDA mandated that all manufacturers of atypical antipsychotics (e.g., risperidone, olanzapine) add a boxed warning to the labeling indicating that increased death rates (1.6-1.7 times that of placebo) have been noted in this patient population receiving atypical antipsychotics. Death typically occurred due to heart failure, sudden death, or infections (primarily pneumonia). In June 2008, this warning was expanded to include all conventional antipsychotics following an FDA review of data which included two population-based, retrospective cohort studies evaluating the risk of death in elderly patients with dementia receiving conventional antipsychotics. One of the studies found that those receiving atypical antipsychotics had an increase in mortality compared to the placebo group, and that those receiving conventional antipsychotics had a marginally higher risk of death compared to the atypical antipsychotic group. The causes of death were not available. Investigators from a separate study reported that the risk of death (all cause mortality) in the conventional antipsychotic group was comparable to and possibly greater than the risk of death in the atypical antipsychotic group. Deaths due to cancer and cardiac disease carried the highest relative risk. In addition, a significantly increased incidence of cerebrovascular events (e.g., stroke, transient ischemic attack), including fatalities, have been reported in the elderly with dementia-related psychosis receiving some atypical antipsychotics. The FDA considers elderly patients with dementia-related psychosis to be at an increased risk for death when treated with any antipsychotic and advises healthcare professionals to discuss this risk with patients and/or their caregivers if treatment is deemed necessary.
Antipsychotics have been reported to disrupt the body's ability to reduce core body temperature presumably through effects in the hypothalamus, and they predispose patients to hyperthermia. Patients receiving thiothixene should be advised of conditions that contribute to an elevation in core body temperature (e.g., strenuous exercise, ambient temperature increase, or dehydration). A less frequently described alteration in thermoregulatory processes reported with both conventional and atypical antipsychotics is hypothermia. Thermoregulation is multi-factorial; however, the dopaminergic system appears to have a primary role, and serotonin may also have modulatory activity (5-HT2a receptors). Most cases of hypothermia associated with antipsychotics have occurred in conjunction with other potential precipitating factors such as hypothyroidism, sepsis, organic brain injury, or environmental temperature. Hypothermia appears to occur more frequently during initiation of antipsychotic therapy or after dose increases.
Thirst and polydipsia have occurred during treatment with antipsychotics. Polydipsia may be psychogenic in nature or a result of antipsychotic-induced metabolic complications such as diabetes; therefore, careful evaluation is recommended. Hyponatremia can develop from polydipsia which can progress to water intoxication, with symptoms such as confusion, lethargy, psychosis, and in severe cases, seizures or death. Some data suggest that antipsychotic-induced hyponatremia is most likely the result of syndrome of inappropriate antidiuretic hormone (SIADH).
Although not reported with thiothixene, evidence indicates there is a relationship between phenothiazine therapy and the occurrence of a systemic lupus erythematosus-like syndrome (lupus-like symptoms).
Tardive dyskinesia is a syndrome of potentially irreversible, involuntary, dyskinetic movements that may develop in patients treated with antipsychotics. Regular evaluation for movement disorders is recommended (e.g., AIMS, DISCUS). Factors associated with a greater susceptibility to tardive dyskinesia include an age above 55 years, female gender, white or African ethnicity, presence of a mood disorder, intellectual disability, CNS injury, prior or current akathisia, significant parkinsonism, or acute dystonic reaction. The rate of tardive dyskinesia in adults treated with a first generation antipsychotic appears to be at least 3 times that observed with second generation antipsychotics. The risk of developing tardive dyskinesia and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotics administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief periods at low doses or may arise after drug discontinuation. Antipsychotics may suppress the signs and symptoms of tardive dyskinesia and thereby mask the underlying process; however, the syndrome may also remit partially or completely if the antipsychotic is withdrawn. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown. If signs and symptoms of tardive dyskinesia appear, thiothixene discontinuation should be considered. However, some patients may require treatment despite the presence of the syndrome.
It is not known whether there is a cross-sensitivity between the thioxanthenes and the phenothiazine derivatives, but this possibility should be considered in patients with reported phenothiazine hypersensitivity. In addition, liver damage (jaundice, biliary stasis) has been reported with related drugs (phenothiazines), so if jaundice occurs with thiothixene use, consider drug discontinuation.
Thiothixene is contraindicated in patients with circulatory collapse (shock). Use thiothixene with caution in patients with cardiac disease. Hypotension induced by thiothixene may be additive with other hypotensive agents and blood pressure should be monitored in such patients; monitor for excessive hypotension. Orthostatic hypotension could lead to syncope or falls with the potential for fractures and other injuries. A fall risk assessment should be completed when initiating an antipsychotic in patients with conditions, diseases, or concurrent medication use that could exacerbate orthostasis. A fall risk assessment should be completed recurrently in at-risk patients on long-term antipsychotic therapy.
Thiothixene should be used with caution in patients with hematological disease. Hematologic effects including leukopenia, neutropenia, and agranulocytosis have been associated with antipsychotic use. Possible risk factors for leukopenia/neutropenia include preexisting low white blood cell count (WBC) and history of drug induced leukopenia/neutropenia. Patients with a history of a clinically significant low WBC or drug induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and discontinuation of thiothixene should be considered at the first sign of a clinically significant decline in WBC in the absence of other causative factors. Patients with clinically significant neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Patients with severe neutropenia (absolute neutrophil count less than 1,000/mm3) should discontinue thiothixene and have their WBC followed until recovery.
Thiothixene and certain other psychotropic drugs can lower the seizure threshold and increase the risk of precipitating convulsions; extreme caution should be used in patients with a history of seizure disorder or those in a state of alcohol withdrawal.
Thiothixene is contraindicated in patients with central nervous system depression (CNS depression) due to any cause and coma. Thiothixene can cause somnolence. Somnolence could lead to falls with the potential for fractures and other injuries. A fall risk assessment should be completed when initiating an antipsychotic and throughout treatment in at-risk patients. Patients receiving thiothixene should be advised to avoid driving or operating machinery until the effects of the drug are known. Given the primary CNS effects of thiothixene, caution should be used during coadministration with other CNS depressants and alcohol. Ethanol ingestion may further impair cognitive and motor skills and patients should be advised to avoid use of alcoholic beverages.
Antipsychotics can cause motor and sensory instability, which may lead to falls with the potential for fractures and other injuries. A fall risk assessment should be completed when initiating an antipsychotic in patients with neurological disease that could exacerbate motor and sensory instability. A fall risk assessment should be completed recurrently in at-risk patients on long-term antipsychotic therapy. Thiothixene use should generally be avoided in patients with Parkinson's disease, as blockade of dopamine receptors centrally by thiothixene may worsen parkinsonian symptoms.
An antiemetic effect was observed in animal studies with thiothixene; since this effect may also occur in humans, it is possible that thiothixene may mask signs of overdosage of toxic drugs and may obscure conditions such as intestinal GI obstruction and brain tumor. Though thiothixene exhibits rather weak anticholinergic properties, use with caution in patients who are receiving atropine or related anticholinergic medications, since the effects on GI, urinary or other systems can be additive.
Antipsychotics have been reported to disrupt the body's ability to reduce core body temperature presumably through effects in the hypothalamus, and they predispose patients to hyperthermia. Patients receiving thiothixene should be advised of conditions that contribute to an elevation in core body temperature (e.g., strenuous exercise, ambient temperature increase, or dehydration). A less frequently described alteration in thermoregulatory processes reported with both conventional and atypical antipsychotics is hypothermia. Thermoregulation is multi-factorial; however, the dopaminergic system appears to have a primary role, and serotonin may also have modulatory activity (5-HT2a receptors). Most cases of hypothermia associated with antipsychotics have occurred in conjunction with other potential precipitating factors such as hypothyroidism, sepsis, organic brain injury, or environmental temperature. Hypothermia appears to occur more frequently during initiation of antipsychotic therapy or after dose increases.
Antipsychotic drugs, including thiothixene, elevate prolactin levels; the elevation (hyperprolactinemia) persists during chronic administration. Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin dependent in vitro, use caution when considering thiothixene treatment in a patient with a previously detected breast cancer. Although disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in relation to elevated prolactin levels, the clinical significance of elevated serum prolactin levels is unknown for most patients. An increase in mammary neoplasms has been found in rodents after chronic administration of antipsychotic drugs. Neither clinical studies nor epidemiologic studies conducted to date, however, have shown an association between chronic administration of these drugs and mammary tumorigenesis; the available evidence is considered too limited to be conclusive at this time.
Thiothixene should be used during pregnancy only when the expected benefits outweigh the potential risks to the mother and fetus. Animal studies and clinical experience have not demonstrated teratogenic effects. Similar findings have been reported with other psychotropic agents. After repeated oral administration of thiothixene to rats (5 to 15 mg/kg/day), rabbits (3 to 50 mg/kg/day), and monkeys (1 to 3 mg/kg/day) before and during gestation, no teratogenic effects were seen. Neonates exposed to antipsychotics during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity and have ranged from self-limited to those requiring intensive care unit support and prolonged hospitalization. Neonates exhibiting signs or symptoms of extrapyramidal effects or withdrawal should be carefully monitored. The knowledge about long-term neurobehavioral effects in offspring is limited for all antipsychotic agents and requires further investigation. According to the American Psychiatric Association treatment guidelines for schizophrenia, consider pregnancy testing in women of childbearing potential prior to initiation of an antipsychotic. The National Pregnancy Registry for Psychiatric Medications is dedicated to evaluating the safety of psychiatric medications that may be taken by women during pregnancy to treat a wide range of mood, anxiety, or psychiatric disorders. One goal of this registry is to determine the frequency of major malformations, such as heart defects, cleft lip, or neural tube defects, in babies exposed to various psychiatric drugs during pregnancy; therefore, patient registration is encouraged. For more information, contact the registry at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry or by phone 1-866-961-2388. It is not known if antipsychotics, through their effect on prolactin, would affect labor or obstetric delivery.
Although no breast-feeding recommendations are available from the manufacturer of thiothixene, related antipsychotics such as phenothiazines are excreted into human breast milk. Thiothixene may induce hyperprolactinemia and galactorrhea, and thus may interfere with proper lactation. Due to individual variability in response to antipsychotics, it may be prudent to continue the existing regimen if ongoing treatment is deemed necessary during breast-feeding; however, alternate medications for consideration include atypical agents such as olanzapine or quetiapine. Data regarding the safety of atypical antipsychotics during breast-feeding are limited and chronic administration of any antipsychotic during breast-feeding should be avoided if possible. Regardless of the antipsychotic used, the nursing infant should be closely monitored for excessive drowsiness, lethargy, and developmental delays. Combination treatment with antipsychotics may increase the risk of these adverse events. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.
The use of thiothixene in children and infants under 12 years of age is not recommended because safe conditions for its use have not been established.
Geriatric adults are more susceptible to the actions and adverse effects of thiothixene and related antipsychotic agents, including tardive dyskinesia, dystonias, orthostatic hypotension, anticholinergic effects, and risk for falls and fractures. Initiate treatment with lower doses followed by careful dosage titration and close monitoring. Thiothixene is not approved for the treatment of dementia-related psychosis in geriatric adults. Geriatric patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. An increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatal events, has also been reported. The Beers Criteria consider antipsychotics to be potentially inappropriate medications (PIMs) in geriatric adults and use should be avoided except for treating schizophrenia or bipolar disorder. In general, avoid use in geriatric patients with delirium, dementia, or Parkinson's disease. Non-pharmacological strategies are first-line options for treating delirium- or dementia-related behavioral problems unless they have failed or are not possible and the patient is a substantial threat to self or others. If antipsychotic use is necessary in those with a history of falls or fractures, consider reducing the use of other CNS depressants and implement other fall risk strategies. Due to the potential for antipsychotic-induced hyponatremia and SIADH, sodium levels should be closely monitored at initiation and after dose changes. The U.S. Omnibus Budget Reconciliation Act (OBRA) regulates antipsychotic use in residents of long-term care facilities (LTCFs) and use must be supported by an appropriate clinical indication that is thoroughly documented within the medical record. When used to manage behavior, stabilize mood, or treat a psychiatric disorder, the facility should attempt to taper the antipsychotic as outlined in the OBRA guidelines, unless a taper is clinically contraindicated. Indications, dosages, and the duration of antipsychotic treatment in the geriatric adult should be in accordance with prescribing labels, published literature recommendations, and expert guidelines. "As needed" (PRN) use for acute behavioral/medical situations in the LTCF must be limited to 14 days, and any use beyond this duration requires that the attending physician/prescribing practitioner evaluate the patient prior to continued use.
Tobacco smoking can induce CYP1A2 hepatic metabolism and may reduce plasma concentrations of thiothixene compared with those of nonsmokers receiving the same dose. Dosage adjustments may be required in some patients who start or stop smoking while receiving thiothixene.
Patients with dysphagia or who are at risk for aspiration should be closely monitored while receiving thiothixene. Antipsychotics have been associated with esophageal dysmotility and aspiration of gastric contents, which may increase the incidence of aspiration pneumonia in susceptible patient populations, such as those with severe Alzheimer's disease.
For the treatment of schizophrenia:
Oral dosage:
Adults: Initially, 2 mg PO 3 times daily or 5 mg PO twice daily, depending on severity of the condition. Increase dosage gradually based upon response and tolerability. In general, a lower initial dosage and slower titration are advisable in geriatric or debilitated patients. The usual optimal dosage is in the range of 20 to 30 mg/day PO given in divided doses, but doses up to 60 mg/day may be necessary for severe conditions. Exceeding 60 mg/day rarely increases the beneficial response. For maintenance therapy, the lowest effective dosage should be used. A single daily dose may be used if desired.
Children and Adolescents 12 to 17 years: Initially, 2 mg PO 3 times daily or 5 mg PO twice daily, depending on the severity of the condition. Increase dosage gradually based upon response and tolerability. The usual optimal dosage is in the range of 20 to 30 mg/day PO given in divided doses, but doses up to 60 mg/day may be necessary for severe conditions. Exceeding 60 mg/day rarely increases the beneficial response. For maintenance therapy, the lowest effective dosage should be used. A single daily dose may be used if desired.
Children 5 to 11 years*: Data are very limited. In children, weight-based dosing is often used. A dose of 0.25 mg/kg/day PO, given in divided doses, has been suggested as an effective dose. In 1 small clinical trial of 10 boys (ages 5 to 15 years) with a diagnosis of autism, schizophrenia, or organic psychosis and inadequate response to prior treatment, the efficacy of thiothixene was compared to placebo alone followed by trihexyphenidyl alone during a run-in period. After the run-in period, trihexyphenidyl was continued as a prophylactic for extrapyramidal symptoms. Thiothixene was initiated at 1 mg/day PO and titrated to response and tolerability. Maximum tolerated dose range: 6 to 60 mg/day (mean 27 mg/day); optimum daily dose ranged from 6 to 30 mg/day (mean 14 mg/day). Analysis of the psychiatric rating scale for children showed significant improvement over both placebo and trihexyphenidyl monotherapy for the following symptoms: quantity and quality of motor activity, quantity of speech, thought content, social relationships, mood, anger, feeding, attention disorder, and emotional unresponsiveness.
For the treatment of severe behavioral or psychological symptoms of dementia* (BPSD)*:
Oral dosage:
Geriatric Adults: 1 to 2 mg PO once or twice per day, initially. Gradually titrate every 4 to 7 days by 1 to 2 mg/day, if needed. Use the lowest effective dosage. Doses above 7 mg/day are rarely needed. First-generation antipsychotics are not considered medications of choice in guidelines/algorithms for BPSD treatment. First-generation antipsychotics are not FDA-approved for this indication and the labeling contains a boxed warning noting an increased risk of death in geriatric patients with dementia.
Maximum Dosage Limits:
-Adults
60 mg/day PO. Debilitated patients require lower dosages.
-Geriatric
60 mg/day PO. Debilitated patients require lower dosages.
-Adolescents
60 mg/day PO. Debilitated patients require lower dosages.
-Children
12 years: 60 mg/day PO. Debilitated patients require lower dosages.
1 to 11 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific data for hepatic impairment are not available; no dosage adjustments in this population have been noted. Patients who develop jaundice secondary to thiothixene use should have therapy discontinued.
Patients with Renal Impairment Dosing
Specific data for renal impairment are not available; no dosage adjustments in this population have been noted.
Intermittent hemodialysis or Peritoneal dialysis
There are no data on the use of peritoneal or hemodialysis with thiothixene, but they are known to be of little value in removing related medications (phenothiazines).
*non-FDA-approved indication
Acebutolol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of opioid agonists like dihydrocodeine with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Avoid prescribing opioid cough medication in patients taking thiothixene.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Acetaminophen; Chlorpheniramine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
Acetaminophen; Codeine: (Moderate) Concomitant use of opioid agonists like codeine with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Avoid prescribing opioid cough medication in patients taking thiothixene.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
Acetaminophen; Diphenhydramine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with thiothixene may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. Additive CNS depression may occur. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of thiothixene could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If thiothixene is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Thiothixene is a weak inhibitor of CYP2D6.
Acetaminophen; Oxycodone: (Moderate) Concomitant use of opioid agonists like oxycodone with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Acetaminophen; Phenylephrine: (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
Acrivastine; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Alfentanil: (Moderate) Concomitant use of opioid agonists like alfentanil with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Aliskiren: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Alpha-blockers: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Alprazolam: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as benzodiazepines. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Amantadine: (Moderate) Although the mechanism of amantadine is not clear, it may potentiate the actions of dopamine. Since thiothixene is a dopamine antagonist, this drug is best avoided when possible in patients with Parkinson's disease who require amantadine therapy.
Amifampridine: (Major) Carefully consider the need for concomitant treatment with thiothixene and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Thiothixene may increase the risk of seizures.
Amiloride: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Aminolevulinic Acid: (Moderate) Thiothixene may increase the effects of photosensitizing agents used during photodynamic therapy. Patients receiving phenothiazines should avoid ultra-violet (UV) exposure whenever possible.
Amitriptyline: (Moderate) Concurrent use of thiothixene and tricyclic antidepressants (TCAs) may result in additive anticholinergic effects, sedation, and orthostatic hypotension. Additive effects may be more pronounced when thiothixene is used with tertiary TCAs including amitriptyline, clomipramine, doxepin, imipramine, and trimipramine versus secondary TCAs such as desipramine, nortriptyline, and protriptyline.
Amlodipine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Amlodipine; Atorvastatin: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Amlodipine; Benazepril: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Amlodipine; Celecoxib: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Amlodipine; Olmesartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Amlodipine; Valsartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Amobarbital: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as general anesthetics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Amoxapine: (Moderate) Use caution during co-administration of amoxapine and thiothixene. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of seizure threshold are potential problems with the combined use of amoxapine and antipsychotics.
Amphetamine: (Major) Concurrent use of antipsychotics, such as thiothixene, and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
Amphetamine; Dextroamphetamine Salts: (Major) Concurrent use of antipsychotics, such as thiothixene, and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
Amphetamine; Dextroamphetamine: (Major) Concurrent use of antipsychotics, such as thiothixene, and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
Angiotensin II receptor antagonists: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Angiotensin-converting enzyme inhibitors: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Anticholinergics: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use.
Apomorphine: (Major) Due to opposing effects on central dopaminergic activity, thiothixene and dopamine agonists may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic instead of thiothixene, if appropriate. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Aripiprazole: (Major) Caution is advisable during concurrent use of aripiprazole with other CNS depressants such as thiothixene. The risk of drowsiness, dizziness, hypotension, extrapyramidal symptoms, anticholinergic effects, neuroleptic malignant syndrome, or seizures may be increased during combined use; therefore, it may be advisable to initiate treatment with lower dosages if combination therapy is deemed necessary. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Articaine; Epinephrine: (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction.
Asenapine: (Major) Caution is advisable during concurrent use of thiothixene and other antipsychotics. Thiothixene use has been associated with adverse events such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Thiothixene can potentiate the CNS-depressant action of the barbiturates. Barbiturates may induce the hepatic metabolism of thiothixene, possibly resulting in decreased neuroleptic effect. Thiothixene does not intensify the anticonvulsant effects of the barbiturates.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs, such skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of opioid agonists like codeine with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Avoid prescribing opioid cough medication in patients taking thiothixene. (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs, such skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Major) Antacids may reduce the oral availablility of thiothixene. To avoid this, administer thiothixene at least 1 hour before or 2 hours after the antacid.
Aspirin, ASA; Oxycodone: (Moderate) Concomitant use of opioid agonists like oxycodone with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Atenolol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Atenolol; Chlorthalidone: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Atropine: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use.
Atropine; Difenoxin: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use.
Azelastine: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including thiothixene.
Azelastine; Fluticasone: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including thiothixene.
Azilsartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Azilsartan; Chlorthalidone: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Baclofen: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs, such skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Belladonna; Opium: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use. (Moderate) Concomitant use of opioid agonists like opium with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Benazepril: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Benzhydrocodone; Acetaminophen: (Moderate) Concomitant use of opioid agonists like benzhydrocodone with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Benzodiazepines: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as benzodiazepines. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use.
Benzphetamine: (Major) Concurrent use of antipsychotics, such as thiothixene, and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
Benztropine: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use.
Betaxolol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Bisoprolol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Brexpiprazole: (Major) Caution is advisable during concurrent use of brexpiprazole with other antipsychotics such as thiothixene. The risk of drowsiness, dizziness, hypotension, extrapyramidal symptoms, anticholinergic effects, neuroleptic malignant syndrome, or seizures may be increased during combined use; therefore, it may be advisable to initiate treatment with lower dosages if combination therapy is deemed necessary. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Bromocriptine: (Major) Avoid concurrent use of thiothixene and bromocriptine when possible. Thiothixene is noted to result in a decreased efficacy of bromocriptine. The prolactin-lowering effect of bromocriptine is antagonized; the elevation in prolactin levels produced by thiothixene persists with chronic administration. However, bromocriptine does not appear to interfere with the antipsychotic effects of thiothixene if it is added to a stable neuroleptic regimen.
Brompheniramine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
Brompheniramine; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
Brompheniramine; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use.
Bumetanide: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Bupivacaine; Epinephrine: (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction.
Bupropion: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored.
Bupropion; Naltrexone: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored.
Buspirone: (Moderate) The combination of buspirone and CNS depressants like thiothixene can increase the risk for sedation.
Butalbital; Acetaminophen: (Moderate) Thiothixene can potentiate the CNS-depressant action of the barbiturates. Barbiturates may induce the hepatic metabolism of thiothixene, possibly resulting in decreased neuroleptic effect. Thiothixene does not intensify the anticonvulsant effects of the barbiturates.
Butalbital; Acetaminophen; Caffeine: (Moderate) Thiothixene can potentiate the CNS-depressant action of the barbiturates. Barbiturates may induce the hepatic metabolism of thiothixene, possibly resulting in decreased neuroleptic effect. Thiothixene does not intensify the anticonvulsant effects of the barbiturates.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of opioid agonists like codeine with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Avoid prescribing opioid cough medication in patients taking thiothixene. (Moderate) Thiothixene can potentiate the CNS-depressant action of the barbiturates. Barbiturates may induce the hepatic metabolism of thiothixene, possibly resulting in decreased neuroleptic effect. Thiothixene does not intensify the anticonvulsant effects of the barbiturates.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of opioid agonists like codeine with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Avoid prescribing opioid cough medication in patients taking thiothixene. (Moderate) Thiothixene can potentiate the CNS-depressant action of the barbiturates. Barbiturates may induce the hepatic metabolism of thiothixene, possibly resulting in decreased neuroleptic effect. Thiothixene does not intensify the anticonvulsant effects of the barbiturates.
Butorphanol: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as butorphanol. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Cabergoline: (Moderate) Cabergoline should not be coadministered with thiothixene due to mutually antagonistic effects on dopaminergic function. The dopamine antagonist action of thiothixene may diminish the prolactin-lowering ability of cabergoline while the dopamine agonist effects of cabergoline may exacerbate a psychotic disorder, reducing the effectiveness of antipsychotics such as thiothixene.
Calcium Carbonate: (Major) Antacids may reduce the oral availablility of thiothixene. To avoid this, administer thiothixene at least 1 hour before or 2 hours after the antacid.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Major) Antacids may reduce the oral availablility of thiothixene. To avoid this, administer thiothixene at least 1 hour before or 2 hours after the antacid.
Calcium Carbonate; Magnesium Hydroxide: (Major) Antacids may reduce the oral availablility of thiothixene. To avoid this, administer thiothixene at least 1 hour before or 2 hours after the antacid.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Major) Antacids may reduce the oral availablility of thiothixene. To avoid this, administer thiothixene at least 1 hour before or 2 hours after the antacid.
Calcium Carbonate; Simethicone: (Major) Antacids may reduce the oral availablility of thiothixene. To avoid this, administer thiothixene at least 1 hour before or 2 hours after the antacid.
Calcium; Vitamin D: (Major) Antacids may reduce the oral availablility of thiothixene. To avoid this, administer thiothixene at least 1 hour before or 2 hours after the antacid.
Calcium-channel blockers: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Candesartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and thiothixene. CNS depressants can potentiate the effects of cannabidiol.
Capsaicin; Metaxalone: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs, such skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Captopril: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Carbamazepine: (Major) Thiothixene, when used concomitantly with carbamazepine, can increase CNS depression and lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when thiothixene is added; monitor for loss of seizure control or the need for dosage adjustments of either the neuroleptic or the anticonvulsant. In addition, carbamazepine is a potent inducer of the cytochrome P-450 mixed-function hepatic oxidase system, and can reduce plasma concentrations of thiothixene to undetectable levels. If thiothixene and carbamazepine must be used together, then dosage adjustments of thiothixene may be required.
Carbidopa; Levodopa: (Major) Due to opposing effects on central dopaminergic activity, thiothixene and levodopa may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to thiothixene. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Carbidopa; Levodopa; Entacapone: (Major) Due to opposing effects on central dopaminergic activity, thiothixene and COMT inhibitors may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to thiothixene. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. (Major) Due to opposing effects on central dopaminergic activity, thiothixene and levodopa may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to thiothixene. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Carbinoxamine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Cariprazine: (Major) Avoid use of these drugs together due to duplicative therapeutic effects and additive risks for drowsiness, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. Cariprazine, like other antipsychotics, has the potential to impair judgment, thinking, or motor skills. The use of cariprazine with other antipsychotic agents, such as thiothixene, would be expected to have additive risks for pharmacologic effects and adverse reactions. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during combined use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Carisoprodol: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs, such skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Carteolol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Carvedilol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Celecoxib; Tramadol: (Moderate) Monitor patients receiving tramadol and thiothixene for serious adverse events including seizures and serotonin syndrome, signs and symptoms that may reflect opioid toxicity, and opioid withdrawal. If thiothixene is discontinued, consider reducing tramadol dosage until stable drug effects are achieved. Monitor patients closely for adverse events including respiratory depression and sedation. Concomitant use of tramadol with thiothixene may result in an increase in tramadol plasma concentrations and a decrease in the concentrations of the active metabolite, M1. A decrease in M1 exposure in patients who have developed physical dependence to tramadol may result in signs and symptoms of opioid withdrawal and reduced efficacy. The effect of increased tramadol concentrations may be an increased risk for serious adverse events including seizures and serotonin syndrome. Discontinuation of thiothixene may result in a decrease in tramadol plasma concentrations and an increase in active metabolite M1 concentrations, which could increase or prolong adverse reactions related to opioid toxicity and may cause potentially fatal respiratory depression. Also, concomitant use of tramadol increases the seizure risk in patients taking thiothixene. Tramadol is a CYP2D6 substrate, and thiothixene is a weak CYP2D6 inhibitor.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and thiothixene. Concurrent use may result in additive CNS depression.
Cetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with thiothixene should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Cetirizine; Pseudoephedrine: (Moderate) Concurrent use of cetirizine/levocetirizine with thiothixene should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Cetrorelix: (Moderate) In the absence of relevant data and as a precaution, drugs that cause hyperprolactinemia including thiothixene should not be administered concomitantly with cetrorelix since hyperprolactinemia downregulates the number of pituitary GnRH receptors.
Charcoal: (Major) The absorption of thiothixene is reduced when coadministered with activated charcoal. Concomitant administration is not recommended, however, coadministration with activated charcoal may be appropriate in certain overdose situations.
Chlophedianol; Dexbrompheniramine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Chlorcyclizine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Chlordiazepoxide: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as benzodiazepines. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Chlordiazepoxide; Amitriptyline: (Moderate) Concurrent use of thiothixene and tricyclic antidepressants (TCAs) may result in additive anticholinergic effects, sedation, and orthostatic hypotension. Additive effects may be more pronounced when thiothixene is used with tertiary TCAs including amitriptyline, clomipramine, doxepin, imipramine, and trimipramine versus secondary TCAs such as desipramine, nortriptyline, and protriptyline. (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as benzodiazepines. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Chlordiazepoxide; Clidinium: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use. (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as benzodiazepines. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Chlorothiazide: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Chlorpheniramine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Chlorpheniramine; Codeine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) Concomitant use of opioid agonists like codeine with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Avoid prescribing opioid cough medication in patients taking thiothixene.
Chlorpheniramine; Dextromethorphan: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Chlorpheniramine; Hydrocodone: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) Concomitant use of hydrocodone with thiothixene may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. Additive CNS depression may occur. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of thiothixene could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If thiothixene is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Thiothixene is a weak inhibitor of CYP2D6.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Chlorpheniramine; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
Chlorpheniramine; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Chlorpromazine: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine antipsychotics. Thiothixene use has been associated with adverse events such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of phenothiazines and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase.
Chlorthalidone: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Chlorzoxazone: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs, such skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Clemastine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Clevidipine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Clobazam: (Major) Clobazam, a benzodiazepine, may cause drowsiness or other CNS effects which may be potentiated during concurrent use of conventional antipsychotics including thiothixene. Antipsychotics may lower the seizure threshold and reduce the effectiveness of clobazam as an anticonvulsant.
Clomipramine: (Moderate) Concurrent use of thiothixene and tricyclic antidepressants (TCAs) may result in additive anticholinergic effects, sedation, and orthostatic hypotension. Additive effects may be more pronounced when thiothixene is used with tertiary TCAs including amitriptyline, clomipramine, doxepin, imipramine, and trimipramine versus secondary TCAs such as desipramine, nortriptyline, and protriptyline.
Clonazepam: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as benzodiazepines. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Clonidine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Clorazepate: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as benzodiazepines. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Clozapine: (Major) Co-administration of clozapine with thiothixene may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures.
Codeine: (Moderate) Concomitant use of opioid agonists like codeine with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Avoid prescribing opioid cough medication in patients taking thiothixene.
Codeine; Guaifenesin: (Moderate) Concomitant use of opioid agonists like codeine with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Avoid prescribing opioid cough medication in patients taking thiothixene.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists like codeine with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Avoid prescribing opioid cough medication in patients taking thiothixene.
Codeine; Phenylephrine; Promethazine: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine antipsychotics. Thiothixene use has been associated with adverse events such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of phenothiazines and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase. (Moderate) Concomitant use of opioid agonists like codeine with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Avoid prescribing opioid cough medication in patients taking thiothixene. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
Codeine; Promethazine: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine antipsychotics. Thiothixene use has been associated with adverse events such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of phenothiazines and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase. (Moderate) Concomitant use of opioid agonists like codeine with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Avoid prescribing opioid cough medication in patients taking thiothixene.
COMT inhibitors: (Major) Due to opposing effects on central dopaminergic activity, thiothixene and COMT inhibitors may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to thiothixene. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Cyclobenzaprine: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs, such skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Cyproheptadine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Dantrolene: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs, such skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Degarelix: (Major) Avoid coadministration of degarelix with thiothixene due to the risk of reduced efficacy of degarelix. Thiothixene can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; degarelix is a GnRH analog.
Desipramine: (Moderate) Concurrent use of thiothixene and tricyclic antidepressants (TCAs) may result in additive anticholinergic effects, sedation, and orthostatic hypotension. Additive effects may be more pronounced when thiothixene is used with tertiary TCAs including amitriptyline, clomipramine, doxepin, imipramine, and trimipramine versus secondary TCAs such as desipramine, nortriptyline, and protriptyline.
Deutetrabenazine: (Major) Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and thiothixene is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Additionally, advise patients that concurrent use of deutetrabenazine and drugs that cause CNS depression, such as thiothixene, may have additive effects and worsen drowsiness or sedation.
Dexbrompheniramine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Dexchlorpheniramine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Dextroamphetamine: (Major) Concurrent use of antipsychotics, such as thiothixene, and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
Dextromethorphan; Bupropion: (Major) Bupropion is associated with a dose-related risk of seizures. Extreme caution is recommended during concurrent use of other drugs that may lower the seizure threshold such as antipsychotics. The manufacturer of bupropion recommends low initial dosing and slow dosage titration if this combination must be used; the patient should be closely monitored.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
Diazepam: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as benzodiazepines. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Diazoxide: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Dicyclomine: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Diltiazem: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Dimenhydrinate: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Diphenhydramine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Diphenhydramine; Ibuprofen: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Diphenhydramine; Naproxen: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Diphenhydramine; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
Diphenoxylate; Atropine: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use.
dopamine agonists: (Major) Due to opposing effects on central dopaminergic activity, thiothixene and dopamine agonists may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic instead of thiothixene, if appropriate. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Dopamine: (Moderate) The vasoconstrictive properties of dopamine infusion can be decreased by the alpha-adrenergic blocking effect of thiothixene. Because the alpha-blocking effect of thiothixene is weak, a significant interaction is unlikely.
Doxazosin: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Doxepin: (Moderate) Concurrent use of thiothixene and tricyclic antidepressants (TCAs) may result in additive anticholinergic effects, sedation, and orthostatic hypotension. Additive effects may be more pronounced when thiothixene is used with tertiary TCAs including amitriptyline, clomipramine, doxepin, imipramine, and trimipramine versus secondary TCAs such as desipramine, nortriptyline, and protriptyline.
Doxorubicin Liposomal: (Major) In vitro, thiothixene is a mild CYP2D6 inhibitor; doxorubicin is a major substrate of CYP2D6. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of thiothixene and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
Doxorubicin: (Major) In vitro, thiothixene is a mild CYP2D6 inhibitor; doxorubicin is a major substrate of CYP2D6. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of thiothixene and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
Doxylamine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Doxylamine; Pyridoxine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Dronabinol: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as dronabinol. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Eliglustat: (Moderate) In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of thiothixene and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily. Thiothixene is a weak CYP2D6 inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration with CYP2D6 inhibitors, such as thiothixene, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias).
Enalapril, Enalaprilat: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Entacapone: (Major) Due to opposing effects on central dopaminergic activity, thiothixene and COMT inhibitors may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to thiothixene. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Ephedrine: (Major) The alpha-adrenergic effects of adrenergic agonists like ephedrine, can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called 'epinephrine reversal,' which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction.
Ephedrine; Guaifenesin: (Major) The alpha-adrenergic effects of adrenergic agonists like ephedrine, can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called 'epinephrine reversal,' which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction.
Epinephrine: (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction.
Eplerenone: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Epoprostenol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Eprosartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Esketamine: (Moderate) Closely monitor patients receiving esketamine and thiothixene for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
Esmolol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Estazolam: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as benzodiazepines. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Eszopiclone: (Moderate) A reduction in the dose of eszopiclone should be considered during co-administration of other CNS depressants, such as thiothixene, to minimize additive sedative effects. In addition, the risk of next-day psychomotor impairment is increased during co-administration of eszopiclone and other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving. Antipsychotics with a higher incidence of sedation, such as olanzapine, clozapine, quetiapine, lurasidone, chlorpromazine, and thioridazine, are more likely to interact with eszopiclone. In one evaluation, concurrent use of eszopiclone and olanzapine reduced psychomotor function as measured by the Digit Symbol Substitution Test (DSST).
Ethacrynic Acid: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
Ethiodized Oil: (Major) Use of medications that lower the seizure threshold, such as thiothixene, should be carefully evaluated when considering intrathecal radiopaque contrast agents. Antipsychotics should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Ethosuximide: (Moderate) Concomitant use of ethosuximide with thiothixene can lower the seizure threshold and reduce the effectiveness of ethosuximide as an anticonvulsant. Additive CNS effects, such as drowsiness, may also occur.
Ethotoin: (Major) Thiothixene, when used concomitantly with various anticonvulsants can increase CNS depression and also can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when thiothixene is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments of either the neuroleptic or the anticonvulsant.
Etomidate: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as general anesthetics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Felodipine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and thiothixene. Concurrent use may result in additive CNS depression.
Fenoldopam: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Fentanyl: (Moderate) Concomitant use of opioid agonists like fentanyl with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Flavoxate: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use.
Fluphenazine: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine antipsychotics. Thiothixene use has been associated with adverse events such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of phenothiazines and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase.
Flurazepam: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as benzodiazepines. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Fosinopril: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Fosphenytoin: (Major) Thiothixene, when used concomitantly with various anticonvulsants can increase CNS depression and also can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when thiothixene is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments of either the neuroleptic or the anticonvulsant.
Furosemide: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Gabapentin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of thiothixene and gabapentin. Concurrent use may result in additive CNS depression.
Ganirelix: (Moderate) In the absence of relevant data and as a precaution, drugs that cause hyperprolactinemia, including thiothixene, should not be administered concomitantly with ganirelix since hyperprolactinemia downregulates the number of pituitary GnRH receptors.
General anesthetics: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as general anesthetics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Glycopyrrolate: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use.
Glycopyrrolate; Formoterol: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use.
Goserelin: (Major) Avoid coadministration of goserelin with thiothixene due to the risk of reduced efficacy of goserelin. Thiothixene can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; goserelin is a GnRH analog.
Guaifenesin; Phenylephrine: (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
Guanfacine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible. In addition, thiothixene can antagonize the pharmacologic actions of guanethidine. Both guanethidine and guanadrel should be avoided in patients receiving thiothixene.
Haloperidol: (Major) Caution is advisable during concurrent use of thiothixene and other antipsychotics. Thiothixene use has been associated with adverse events such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of loxapine and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Histrelin: (Major) Avoid coadministration of histrelin with thiothixene due to the risk of reduced efficacy of histrelin. Thiothixene can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog.
Homatropine; Hydrocodone: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use. (Moderate) Concomitant use of hydrocodone with thiothixene may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. Additive CNS depression may occur. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of thiothixene could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If thiothixene is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Thiothixene is a weak inhibitor of CYP2D6.
Hydantoins: (Major) Thiothixene, when used concomitantly with various anticonvulsants can increase CNS depression and also can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when thiothixene is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments of either the neuroleptic or the anticonvulsant.
Hydralazine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Hydrocodone: (Moderate) Concomitant use of hydrocodone with thiothixene may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. Additive CNS depression may occur. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of thiothixene could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If thiothixene is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Thiothixene is a weak inhibitor of CYP2D6.
Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with thiothixene may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. Additive CNS depression may occur. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of thiothixene could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If thiothixene is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Thiothixene is a weak inhibitor of CYP2D6.
Hydromorphone: (Moderate) Concomitant use of opioid agonists like hydromorphone with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Hydroxyzine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Hyoscyamine: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use.
Ibuprofen; Oxycodone: (Moderate) Concomitant use of opioid agonists like oxycodone with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Iloperidone: (Major) Caution is advisable during concurrent use of thiothixene and other antipsychotics. Thiothixene use has been associated with adverse events such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of loxapine and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Iloprost: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Imipramine: (Moderate) Concurrent use of thiothixene and tricyclic antidepressants (TCAs) may result in additive anticholinergic effects, sedation, and orthostatic hypotension. Additive effects may be more pronounced when thiothixene is used with tertiary TCAs including amitriptyline, clomipramine, doxepin, imipramine, and trimipramine versus secondary TCAs such as desipramine, nortriptyline, and protriptyline.
Indacaterol; Glycopyrrolate: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use.
Indapamide: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Iodixanol: (Major) Use of medications that lower the seizure threshold, such as thiothixene, should be carefully evaluated when considering intrathecal radiopaque contrast agents. Antipsychotics should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iohexol: (Major) Use of medications that lower the seizure threshold, such as thiothixene, should be carefully evaluated when considering intrathecal radiopaque contrast agents. Antipsychotics should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iomeprol: (Major) Use of medications that lower the seizure threshold, such as thiothixene, should be carefully evaluated when considering intrathecal radiopaque contrast agents. Antipsychotics should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iopamidol: (Major) Use of medications that lower the seizure threshold, such as thiothixene, should be carefully evaluated when considering intrathecal radiopaque contrast agents. Antipsychotics should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iopromide: (Major) Use of medications that lower the seizure threshold, such as thiothixene, should be carefully evaluated when considering intrathecal radiopaque contrast agents. Antipsychotics should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Ioversol: (Major) Use of medications that lower the seizure threshold, such as thiothixene, should be carefully evaluated when considering intrathecal radiopaque contrast agents. Antipsychotics should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Irbesartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Isocarboxazid: (Moderate) Concurrent use of monoamine oxidase inhibitors (MAOIs) and thiothixene may prolong or intensify the hypotensive, anticholinergic, or sedative effects of either agent. Due to the potential for additive CNS and cardiovascular effects, MAOIs and thiothixene should be used together cautiously.
Isoflurane: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as general anesthetics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Limited data suggest that rifampin can increase the metabolism or reduce the bioavailability of thiothixene. Dosage adjustments of thiothixene may be necessary following the addition of rifampin or another rifamycin (e.g., rifabutin, rifapentine).
Isoniazid, INH; Rifampin: (Major) Limited data suggest that rifampin can increase the metabolism or reduce the bioavailability of thiothixene. Dosage adjustments of thiothixene may be necessary following the addition of rifampin or another rifamycin (e.g., rifabutin, rifapentine).
Isosulfan Blue: (Major) Use of medications that lower the seizure threshold, such as thiothixene, should be carefully evaluated when considering intrathecal radiopaque contrast agents. Antipsychotics should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Isradipine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Ketamine: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as general anesthetics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Labetalol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and thiothixene. Concurrent use may result in additive CNS depression.
Leuprolide: (Major) Avoid coadministration of leuprolide with thiothixene due to the risk of reduced efficacy of leuprolide. Thiothixene can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
Leuprolide; Norethindrone: (Major) Avoid coadministration of leuprolide with thiothixene due to the risk of reduced efficacy of leuprolide. Thiothixene can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
Levamlodipine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Levocetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with thiothixene should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Levodopa: (Major) Due to opposing effects on central dopaminergic activity, thiothixene and levodopa may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to thiothixene. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Levorphanol: (Moderate) Concomitant use of opioid agonists like levorphanol with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Lidocaine; Epinephrine: (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction.
Lisdexamfetamine: (Major) Concurrent use of antipsychotics, such as thiothixene, and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
Lisinopril: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Lithium: (Moderate) It is advisable to monitor patients for neurotoxicity during co-administration of lithium and thiothixene. Although conventional antipsychotics are considered a treatment option as adjuncts to mood stabilizers such as lithium, neuroleptic malignant syndrome (NMS) and extrapyramidal effects have been observed occasionally during concurrent use. Early case reports described an encephalopathic syndrome consisting of delirium, tremulousness, dyskinesia, seizures, leukocytosis, weakness, hyperpyrexia, confusion, extrapyramidal symptoms, elevations in laboratory values (e.g., liver function tests, blood urea nitrogen, fasting blood sugar) and, in some cases, irreversible brain damage, during use of lithium and conventional antipsychotics, particularly haloperidol. Subsequent rare reports of NMS or NMS-like reactions have been described during co-administration of lithium and atypical antipsychotics (e.g., risperidone, olanzapine, clozapine). Following resolution of NMS, there are isolated instances of re-emergence of symptoms following re-initiation of lithium as monotherapy. Lithium may be a risk factor for antipsychotic-induced NMS; however, this hypothesis has not been confirmed. In many reported cases, confounding factors have been present (e.g., previous history of NMS, high dose therapy). The ability of antipsychotics alone to precipitate NMS and the rarity of the condition further complicate assessment of lithium as a risk factor.
Lofexidine: (Moderate) Monitor for excessive sedation during concurrent use of lofexidine and thiothixene. Lofexidine can potentiate the effects of CNS depressants, including thiothixene.
Loop diuretics: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Lorazepam: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as benzodiazepines. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Losartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Loxapine: (Major) Caution is advisable during concurrent use of loxapine and other antipsychotics. Loxapine use has been associated with adverse events such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of loxapine and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Lumateperone: (Moderate) Coadministration of antipsychotics, such as lumateperone and thiothixene, may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from antipsychotic combinations has not been established and data are very limited, the risk may be increased during combined use versus use of an antipsychotic alone.
Lurasidone: (Major) Similar to other antipsychotics, lurasidone administration has been associated with drowsiness, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. The risk of these adverse effects may be increased during concurrent use of lurasidone with other antipsychotics. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Mecamylamine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Meclizine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Meperidine: (Moderate) Concomitant use of opioid agonists like meperidine with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Meprobamate: (Moderate) Coadministration of meprobamate and thiothixene may result in additive CNS depressant effects.
Metaxalone: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs, such skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Methadone: (Moderate) Concomitant use of opioid agonists like methadone with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Methamphetamine: (Major) Concurrent use of antipsychotics, such as thiothixene, and amphetamines should generally be avoided. Antipsychotics and amphetamines may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Amphetamines are thought to block central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of amphetamines.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use.
Methohexital: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as methohexital. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Methscopolamine: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use.
Methyldopa: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible. Concurrent administration of thiothixene and methyldopa has been reported to cause dementia in some cases. The clinical importance of this interaction has not been established.
Metoclopramide: (Contraindicated) Avoid metoclopramide in patients receiving thiothixene due to potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Some manufacturer labels for metoclopramide contraindicate the use of these drugs together, while others state avoidance is necessary. If these agents must be used together, monitor closely for movement disorders and additive CNS effects. Discontinue these medications at the first signs of dyskinesia. In addition, both drugs may cause sedation, seizures, or increased prolactin levels.
Metolazone: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Metoprolol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Metyrosine: (Moderate) Because it also blocks central dopamine receptors, metyrosine, should be avoided or used cautiously in patients receiving thiothixene to minimize the risk of additive adverse CNS effects.
Midazolam: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as benzodiazepines. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Minoxidil: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Moexipril: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Molindone: (Major) Close monitoring is advisable during concurrent use of molindone with other antipsychotics. Because molindone shares certain pharmacological properties with other antipsychotics, additive cardiac effects (e.g., hypotension), CNS effects (e.g., drowsiness), or anticholinergic effects (e.g., constipation, xerostomia) may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Monoamine oxidase inhibitors: (Moderate) Concurrent use of monoamine oxidase inhibitors (MAOIs) and thiothixene may prolong or intensify the hypotensive, anticholinergic, or sedative effects of either agent. Due to the potential for additive CNS and cardiovascular effects, MAOIs and thiothixene should be used together cautiously.
Morphine: (Moderate) Concomitant use of opioid agonists like morphine with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Morphine; Naltrexone: (Moderate) Concomitant use of opioid agonists like morphine with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Nabilone: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as nabilone. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Nadolol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Nalbuphine: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as nalbuphine. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Nebivolol: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with thiothixene. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as thiothixene, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible.
Nebivolol; Valsartan: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with thiothixene. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as thiothixene, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible. (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Neostigmine; Glycopyrrolate: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use.
Nicardipine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
NIFEdipine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Nimodipine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Nisoldipine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Nitroprusside: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Non-Ionic Contrast Media: (Major) Use of medications that lower the seizure threshold, such as thiothixene, should be carefully evaluated when considering intrathecal radiopaque contrast agents. Antipsychotics should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Norepinephrine: (Major) The alpha-adrenergic effects of adrenergic agonists like norepinephrine, can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called 'epinephrine reversal,' which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction.
Nortriptyline: (Moderate) Concurrent use of thiothixene and tricyclic antidepressants (TCAs) may result in additive anticholinergic effects, sedation, and orthostatic hypotension. Additive effects may be more pronounced when thiothixene is used with tertiary TCAs including amitriptyline, clomipramine, doxepin, imipramine, and trimipramine versus secondary TCAs such as desipramine, nortriptyline, and protriptyline.
Olanzapine: (Major) Caution is advisable during concurrent use of thiothixene and other antipsychotics. Thiothixene use may be associated with adverse events such as drowsiness, dizziness, hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of thiothixene and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Olanzapine; Fluoxetine: (Major) Caution is advisable during concurrent use of thiothixene and other antipsychotics. Thiothixene use may be associated with adverse events such as drowsiness, dizziness, hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of thiothixene and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Olanzapine; Samidorphan: (Major) Caution is advisable during concurrent use of thiothixene and other antipsychotics. Thiothixene use may be associated with adverse events such as drowsiness, dizziness, hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of thiothixene and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Oliceridine: (Moderate) Concomitant use of opioid agonists like oliceridine with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Olmesartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Omeprazole; Amoxicillin; Rifabutin: (Major) Limited data suggest that rifampin can increase the metabolism or reduce the bioavailability of thiothixene. Dosage adjustments of thiothixene may be necessary following the addition of rifampin or another rifamycin (e.g., rifabutin, rifapentine).
Omeprazole; Sodium Bicarbonate: (Major) Antacids may reduce the oral availablility of thiothixene. To avoid this, administer thiothixene at least 1 hour before or 2 hours after the antacid.
Opicapone: (Major) Due to opposing effects on central dopaminergic activity, thiothixene and COMT inhibitors may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to thiothixene. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Orphenadrine: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs, such skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Oxazepam: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as benzodiazepines. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Oxybutynin: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use.
Oxycodone: (Moderate) Concomitant use of opioid agonists like oxycodone with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Oxymorphone: (Moderate) Concomitant use of opioid agonists like oxymorphone with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Paliperidone: (Major) Coadministration of antipsychotics, including paliperidone and thiothixene, should be avoided if possible. Coadministration may increase the risk of adverse events such as drowsiness, dizziness, hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Paroxetine: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with thiothixene is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and thiothixene is a weak CYP2D6 inhibitor. Coadministration with a weak CYP2D6 inhibitor increased paroxetine overall exposure by 50%.
Pentazocine; Naloxone: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as pentazocine. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Pentobarbital: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as pentobarbital. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. The pre-anesthesia administration of thiothixene may increase the hypotensive effects of barbiturate anesthetics. Due to a lowering of seizure threshold by thiothixene, adequate barbiturate therapy should be maintained, if administered for anticonvulsant purposes, when thiothixene is added.
Perindopril: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Perindopril; Amlodipine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Perphenazine: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine antipsychotics. Thiothixene use has been associated with adverse events such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of phenothiazines and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase.
Perphenazine; Amitriptyline: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine antipsychotics. Thiothixene use has been associated with adverse events such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of phenothiazines and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase. (Moderate) Concurrent use of thiothixene and tricyclic antidepressants (TCAs) may result in additive anticholinergic effects, sedation, and orthostatic hypotension. Additive effects may be more pronounced when thiothixene is used with tertiary TCAs including amitriptyline, clomipramine, doxepin, imipramine, and trimipramine versus secondary TCAs such as desipramine, nortriptyline, and protriptyline.
Phenelzine: (Moderate) Concurrent use of monoamine oxidase inhibitors (MAOIs) and thiothixene may prolong or intensify the hypotensive, anticholinergic, or sedative effects of either agent. Due to the potential for additive CNS and cardiovascular effects, MAOIs and thiothixene should be used together cautiously.
Phenobarbital: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as phenobarbital. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. The pre-anesthesia administration of thiothixene may increase the hypotensive effects of barbiturate anesthetics. Due to a lowering of seizure threshold by thiothixene, adequate barbiturate therapy should be maintained, if administered for anticonvulsant purposes, when thiothixene is added.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use. (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as phenobarbital. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. The pre-anesthesia administration of thiothixene may increase the hypotensive effects of barbiturate anesthetics. Due to a lowering of seizure threshold by thiothixene, adequate barbiturate therapy should be maintained, if administered for anticonvulsant purposes, when thiothixene is added.
Phenothiazines: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine antipsychotics. Thiothixene use has been associated with adverse events such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of phenothiazines and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase.
Phenoxybenzamine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Phentolamine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Phenylephrine: (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
Phenytoin: (Major) Thiothixene, when used concomitantly with various anticonvulsants can increase CNS depression and also can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when thiothixene is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments of either the neuroleptic or the anticonvulsant.
Photosensitizing agents (topical): (Moderate) Thiothixene may increase the effects of photosensitizing agents used during photodynamic therapy. Patients receiving phenothiazines should avoid ultra-violet (UV) exposure whenever possible.
Pimozide: (Major) Caution is advisable during concurrent use of thiothixene and other antipsychotics. Thiothixene use has been associated with adverse events such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of loxapine and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Pindolol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Potassium-sparing diuretics: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Pramipexole: (Major) Due to opposing effects on central dopaminergic activity, thiothixene and dopamine agonists may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic instead of thiothixene, if appropriate. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Prazosin: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Pregabalin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of thiothixene and pregabalin. Concurrent use may result in additive CNS depression.
Prilocaine; Epinephrine: (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction.
Primidone: (Moderate) Barbiturates such as primidone may have additive CNS depressant effects, such as sedation, with thiothixene. Antipsychotics, such as thiothixene, may lower the seizure threshold, resulting in an exacerbation of symptoms in patients with a seizure disorder. Due to a lowering of seizure threshold by thiothixene, adequate barbiturate therapy should be maintained, if administered for anticonvulsant purposes, when thiothixene is added.
Prochlorperazine: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine antipsychotics. Thiothixene use has been associated with adverse events such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of phenothiazines and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase.
Promethazine: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine antipsychotics. Thiothixene use has been associated with adverse events such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of phenothiazines and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase.
Promethazine; Dextromethorphan: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine antipsychotics. Thiothixene use has been associated with adverse events such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of phenothiazines and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase.
Promethazine; Phenylephrine: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine antipsychotics. Thiothixene use has been associated with adverse events such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of phenothiazines and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase. (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. Patients taking thiothixene can have reduced pressor response to phenylephrine.
Propafenone: (Major) Propafenone prolongs the QT interval. Combined use with thiothixene could lead to additive orthostatic hypotension and/or prolonged QT syndrome and torsade de pointes. If concomitant use unavoidable, use together with caution and close monitoring.
Propantheline: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use.
Propofol: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as general anesthetics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Propranolol: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Protriptyline: (Moderate) Concurrent use of thiothixene and tricyclic antidepressants (TCAs) may result in additive anticholinergic effects, sedation, and orthostatic hypotension. Additive effects may be more pronounced when thiothixene is used with tertiary TCAs including amitriptyline, clomipramine, doxepin, imipramine, and trimipramine versus secondary TCAs such as desipramine, nortriptyline, and protriptyline.
Pseudoephedrine; Triprolidine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Quazepam: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as benzodiazepines. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Quetiapine: (Major) Caution is advisable during concurrent use of thiothixene and other antipsychotics. Thiothixene use may be associated with adverse events such as drowsiness, dizziness, hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of thiothixene and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Quinapril: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Ramipril: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Rasagiline: (Major) Due to opposing effects on central dopaminergic activity, thiothixene and rasagiline may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to thiothixene. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Remifentanil: (Moderate) Concomitant use of opioid agonists like remifentanil with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Remimazolam: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as benzodiazepines. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Rifabutin: (Major) Limited data suggest that rifampin can increase the metabolism or reduce the bioavailability of thiothixene. Dosage adjustments of thiothixene may be necessary following the addition of rifampin or another rifamycin (e.g., rifabutin, rifapentine).
Rifampin: (Major) Limited data suggest that rifampin can increase the metabolism or reduce the bioavailability of thiothixene. Dosage adjustments of thiothixene may be necessary following the addition of rifampin or another rifamycin (e.g., rifabutin, rifapentine).
Rifamycins: (Major) Limited data suggest that rifampin can increase the metabolism or reduce the bioavailability of thiothixene. Dosage adjustments of thiothixene may be necessary following the addition of rifampin or another rifamycin (e.g., rifabutin, rifapentine).
Rifapentine: (Major) Limited data suggest that rifampin can increase the metabolism or reduce the bioavailability of thiothixene. Dosage adjustments of thiothixene may be necessary following the addition of rifampin or another rifamycin (e.g., rifabutin, rifapentine).
Risperidone: (Major) Co-administration of risperidone with thiothixene may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Ropinirole: (Major) Due to opposing effects on central dopaminergic activity, thiothixene and dopamine agonists may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic instead of thiothixene, if appropriate. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Rotigotine: (Major) Due to opposing effects on central dopaminergic activity, thiothixene and rotigotine may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to thiothixene. In addition, coadministration may result in additive sedation. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Sacubitril; Valsartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Safinamide: (Major) Due to opposing effects on central dopaminergic activity, thiothixene and safinamide may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to thiothixene. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Scopolamine: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use.
Secobarbital: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as secobarbital. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. The pre-anesthesia administration of thiothixene may increase the hypotensive effects of barbiturate anesthetics. Due to a lowering of seizure threshold by thiothixene, adequate barbiturate therapy should be maintained, if administered for anticonvulsant purposes, when thiothixene is added.
Sedating H1-blockers: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Selegiline: (Major) Due to opposing effects on central dopaminergic activity, thiothixene and selegiline may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to thiothixene. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Sevoflurane: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as general anesthetics. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Skeletal Muscle Relaxants: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs, such skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Sodium Bicarbonate: (Major) Antacids may reduce the oral availablility of thiothixene. To avoid this, administer thiothixene at least 1 hour before or 2 hours after the antacid.
Solifenacin: (Moderate) Additive anticholinergic effects may be seen when thiothixene is used concomitantly with other drugs having anticholinergic activity such as solifenacin. Monitor for anticholinergic-related adverse effects such as constipation, blurred vision, and urinary retention during concurrent use.
Spironolactone: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and thiothixene. CNS depressants can potentiate the effects of stiripentol.
Sufentanil: (Moderate) Concomitant use of opioid agonists like sufentanil with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Tapentadol: (Moderate) Concomitant use of opioid agonists like tapentadol with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Telmisartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Telmisartan; Amlodipine: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Temazepam: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as benzodiazepines. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Terazosin: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Tetrabenazine: (Major) Concurrent use of thiothixene and tetrabenazine should generally be avoided since the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, neuroleptic malignant syndrome, or extrapyramidal symptoms may be increased.
Thalidomide: (Major) Avoid the concomitant use of thalidomide with antipsychotics due to the potential for additive sedative effects.
Thiazide diuretics: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Thioridazine: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine antipsychotics. Thiothixene use has been associated with adverse events such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of phenothiazines and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase.
Tizanidine: (Moderate) Concurrent use of tizanidine and antipsychotics like thiothixene can cause additive CNS depression.
Tolcapone: (Major) Due to opposing effects on central dopaminergic activity, thiothixene and COMT inhibitors may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to thiothixene. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Torsemide: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Tramadol: (Moderate) Monitor patients receiving tramadol and thiothixene for serious adverse events including seizures and serotonin syndrome, signs and symptoms that may reflect opioid toxicity, and opioid withdrawal. If thiothixene is discontinued, consider reducing tramadol dosage until stable drug effects are achieved. Monitor patients closely for adverse events including respiratory depression and sedation. Concomitant use of tramadol with thiothixene may result in an increase in tramadol plasma concentrations and a decrease in the concentrations of the active metabolite, M1. A decrease in M1 exposure in patients who have developed physical dependence to tramadol may result in signs and symptoms of opioid withdrawal and reduced efficacy. The effect of increased tramadol concentrations may be an increased risk for serious adverse events including seizures and serotonin syndrome. Discontinuation of thiothixene may result in a decrease in tramadol plasma concentrations and an increase in active metabolite M1 concentrations, which could increase or prolong adverse reactions related to opioid toxicity and may cause potentially fatal respiratory depression. Also, concomitant use of tramadol increases the seizure risk in patients taking thiothixene. Tramadol is a CYP2D6 substrate, and thiothixene is a weak CYP2D6 inhibitor.
Tramadol; Acetaminophen: (Moderate) Monitor patients receiving tramadol and thiothixene for serious adverse events including seizures and serotonin syndrome, signs and symptoms that may reflect opioid toxicity, and opioid withdrawal. If thiothixene is discontinued, consider reducing tramadol dosage until stable drug effects are achieved. Monitor patients closely for adverse events including respiratory depression and sedation. Concomitant use of tramadol with thiothixene may result in an increase in tramadol plasma concentrations and a decrease in the concentrations of the active metabolite, M1. A decrease in M1 exposure in patients who have developed physical dependence to tramadol may result in signs and symptoms of opioid withdrawal and reduced efficacy. The effect of increased tramadol concentrations may be an increased risk for serious adverse events including seizures and serotonin syndrome. Discontinuation of thiothixene may result in a decrease in tramadol plasma concentrations and an increase in active metabolite M1 concentrations, which could increase or prolong adverse reactions related to opioid toxicity and may cause potentially fatal respiratory depression. Also, concomitant use of tramadol increases the seizure risk in patients taking thiothixene. Tramadol is a CYP2D6 substrate, and thiothixene is a weak CYP2D6 inhibitor.
Trandolapril: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Trandolapril; Verapamil: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Tranylcypromine: (Moderate) Concurrent use of monoamine oxidase inhibitors (MAOIs) and thiothixene may prolong or intensify the hypotensive, anticholinergic, or sedative effects of either agent. Due to the potential for additive CNS and cardiovascular effects, MAOIs and thiothixene should be used together cautiously.
Trazodone: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as trazodone. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Treprostinil: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Triamterene: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Triazolam: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs such as benzodiazepines. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Tricyclic antidepressants: (Moderate) Concurrent use of thiothixene and tricyclic antidepressants (TCAs) may result in additive anticholinergic effects, sedation, and orthostatic hypotension. Additive effects may be more pronounced when thiothixene is used with tertiary TCAs including amitriptyline, clomipramine, doxepin, imipramine, and trimipramine versus secondary TCAs such as desipramine, nortriptyline, and protriptyline.
Trifluoperazine: (Major) Caution is advisable during concurrent use of thiothixene and the phenothiazine antipsychotics. Thiothixene use has been associated with adverse events such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of phenothiazines and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone. Administration of thiothixene with antipsychotics that are metabolized by CYP2D6, such as phenothiazines, should be approached with great caution. Thiothixene has been shown to inhibit CYP2D6 in vitro and serum concentrations of phenothiazines may increase.
Trihexyphenidyl: (Moderate) Anticholinergics may have additive effects with thiothixene, an antipsychotic with the potential for anticholinergic activity. Monitor for anticholinergic-related adverse effects such as xerostomia, blurred vision, constipation, and urinary retention during concurrent use.
Trimipramine: (Moderate) Concurrent use of thiothixene and tricyclic antidepressants (TCAs) may result in additive anticholinergic effects, sedation, and orthostatic hypotension. Additive effects may be more pronounced when thiothixene is used with tertiary TCAs including amitriptyline, clomipramine, doxepin, imipramine, and trimipramine versus secondary TCAs such as desipramine, nortriptyline, and protriptyline.
Triprolidine: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Triptorelin: (Major) Avoid coadministration of triptorelin with thiothixene due to the risk of reduced efficacy of triptorelin. Thiothixene can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog.
Trospium: (Moderate) Additive anticholinergic effects may be seen when thiothixene is used concomitantly with other drugs having anticholinergic activity such as trospium. Monitor for anticholinergic-related adverse effects such as constipation, blurred vision, and urinary retention during concurrent use.
Valproic Acid, Divalproex Sodium: (Major) Thiothixene, when used concomitantly with various anticonvulsants, such as valproic acid, can increase CNS depression and also can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when thiothixene is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments of either the neuroleptic or the anticonvulsant.
Valsartan: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Vasodilators: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Verapamil: (Moderate) Thiothixene should be used cautiously in patients receiving antihypertensive agents. Additive hypotensive effects are possible.
Vigabatrin: (Major) Vigabatrin should not be used with thiothixene, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Zaleplon: (Moderate) Coadministration of zaleplon and antipsychotics like thiothixene can result in additive CNS depressant effects. In premarketing studies, zaleplon potentiated the CNS effects of ethanol, imipramine, and thioridazine for at least 2 to 4 hours. A similar interaction may occur with other antipsychotics.
Ziprasidone: (Major) Caution is advisable during concurrent use of thiothixene and other antipsychotics. Thiothixene use has been associated with adverse events such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of loxapine and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Zolpidem: (Moderate) Zolpidem and thiothixene may have cumulative effects on CNS depression when administered concurrently and they should be used together with caution. In addition, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of zolpidem and other CNS depressants than with zolpidem alone.
Zonisamide: (Moderate) Zonisamide may cause decreased sweating (oligohidrosis), elevated body temperature (hyperthermia), heat intolerance, or heat stroke. The manufacturer recommends caution in using concurrent drug therapies that may predispose patients to heat-related disorders such as antipsychotics. Monitor patients for heat intolerance, decreased sweating, or increased body temperature if zonisamide is used with any of these agents.
Zuranolone: (Major) Avoid the use of multiple sedating agents due to the risk for additive CNS depression. If use is necessary, consider a downward dosage adjustment of either or both medications, especially in patients with additional risk factors for sedation-related harm.
Thiothixene blocks postsynaptic dopamine receptors in the mesolimbic system and increases dopamine turnover by blockade of the D2 somatodendritic autoreceptor. After approximately 12 weeks of chronic therapy, depolarization blockade of dopamine tracts occurs. The decrease in dopamine neurotransmission has been found to correlate with the antipsychotic effects. This D2 blockade is also responsible for the potent extrapyramidal effects observed with this drug. Dopamine blockade in the chemoreceptor trigger zone accounts for the antiemetic effects. Thiothixene possesses weak anticholinergic and alpha-adrenergic receptor blocking effects. Blockade of alpha1-adrenergic receptors produces sedation; muscle relaxation; and cardiovascular effects such as hypotension, reflex tachycardia, and minor changes in ECG patterns.
Thiothixene is administered orally. Distribution is extensive, and the drug can be detected in the body for several weeks after use. Protein binding is 90%. Metabolism takes place in the liver, but large amounts of drug are excreted with metabolites in the feces, via the bile. Although thiothixene is primarily metabolized by CYP1A2, no specific metabolites have been noted. The elimination is biphasic, with an initial half-life of 3.4 hours and a terminal half-life of 34 hours.
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP1A2
Thiothixene is a major substrate of CYP1A2. Data from a small retrospective study indicated that tobacco smokers had a higher clearance of thiothixene than non-smokers. In addition, the daily dose of thiothixene was an average of 45% higher in the smoking group than the non-smoking group. In the same study, use with CYP1A2 enzyme-inducing drugs, including carbamazepine and phenytoin, also resulted in a significant increase in clearance. Thiothixene has been shown to weakly inhibit CYP2D6 in vitro; however, the clinical significance is unknown.
-Route-Specific Pharmacokinetics
Oral Route
Following oral administration, the absorption of thiothixene is erratic, with an approximate 50% bioavailability. Peak concentrations occur 1 to 2 hours following a dose.
-Special Populations
Hepatic Impairment
Specific pharmacokinetic data in patients with hepatic impairment are not available.
Renal Impairment
Specific pharmacokinetic data in patients with renal impairment are not available.
Other
Smoking
Tobacco smoking may reduce thiothixene plasma concentrations via CYP1A2 induction.