Thioxanthene (Oral, Parenteral)

Thioxanthene is an antipsychotic medication commonly prescribed to individuals with schizophrenia.

Overview

Thioxanthene is an antipsychotic agent used to treat mental, nervous and emotional conditions such as schizophrenia. It works by manipulating key nerve pathways in the brain which are understood to be responsible for psychosis and similar mental health conditions. It isn't suitable for treatment of dementia-related psychosis.

The drug is a central nervous system (CNS) depressant and should be used with caution in individuals who are taking other medications which work on the central nervous system. It is associated with an involuntary movement syndrome called tardive dyskinesia which can cause uncontrollable movements of the mouth, tongue, cheeks, hands, arms and legs. The longer an individual takes thioxanthene for, the higher their risk of developing tardive dyskinesia becomes. For this reason, the drug is designed to be used for the shortest time possible and is avoided for long-term, chronic use. However, it does take several weeks before its fullest effects are reached.

Thioxanthene is available in liquid, capsule, tablet and solution dosage forms, and in the US the most common brand name for the drug is Navane.

Condition(s) treated?

  • Psychosis
  • Schizophrenia

Type of medicine?

  • Antipsychotic

Side Effects

One of the most serious side effects associated with thioxanthene use is tardive dyskinesia. The syndrome causes involuntary movements in the mouth, tongue, jaw, arms and legs, and it can be permanent even after thioxanthene is discontinued. Look out for symptoms of tardive dyskinesia and, if you think you may have it, consult a doctor as soon as possible.

The following symptoms of tardive dyskinesia are very serious and require emergency medical attention:

  • Difficulty breathing
  • Fast heartbeat
  • Seizures
  • High fever
  • Unusually high or low blood pressure
  • Severe muscle stiffness
  • Loss of bladder control

Less serious symptoms of tardive dyskinesia include:

  • Twitches or grimacing
  • Puckering of the lips or lip smacking
  • Puffing of cheeks
  • Uncontrollable chewing movements
  • Spasms in neck and back
  • Sudden movements in the arms, legs or hands
  • Muscle rigidity
  • Unusual tiredness
  • Poor balance
  • Severe restlessness
  • Trembling of fingers and hands
  • Twisting movements in body
  • Uncontrollable arm and leg movements
  • Shuffling walk
  • Increased blinking or spasms in eyelid

The following symptoms may or may not be caused by tardive dyskinesia, but they should still be reported to a doctor urgently:

  • Blurred vision
  • Unusually pale skin
  • Difficult urination
  • Skin rash
  • Discoloration of skin
  • Hot, dry skin without sweating
  • Sore throat and fever
  • Unusual bleeding or bruising
  • Yellow eyes and skin

The following side effects are minor and do not necessarily require treatment unless they cause major inconvenience and persist for a long time. If you're concerned about them, discuss them with your doctor. Many people find that minor side effects diminish after taking thioxanthene for a little while, since the body adjusts to the effects of the drug:

  • Constipation
  • Increased appetite and subsequent weight gain
  • Nausea
  • Reduced or increased sweating
  • Dizziness, lightheadedness, feeling faint or fainting
  • Increases sensitivity to sunlight, such as skin rash, irritation, redness or severe sunburn
  • Mild drowsiness
  • Dry mouth or increased salivation
  • Stuffy nose
  • Abnormal changes to menstrual period
  • Swelling of breasts in both men and women
  • Unusual secretion of breast milk in women
  • Impotence or reduction in sex drive or sexual function

If you notice any other side effects not listed here, consult your doctor or report the side effects to the FDA.

Overdose of thioxanthene

Taking too much thioxanthene can be incredibly dangerous. If you think you may have taken too much of the drug, seek emergency care, whether you experience symptoms of overdose or not. Symptoms of thioxanthene overdose include:

  • Severe breathing difficulty
  • Severe dizziness
  • Severe drowsiness
  • Severe muscle trembling, jerking or stiffness
  • Small pupils
  • Extreme excitement
  • Extreme lethargy or weakness

Allergic reaction to thioxanthene

Although rare, there have been instances of an allergic reaction to thioxanthene. If you notice any signs of allergy or anaphylaxis, discontinue the use of the drug and seek emergency medical care. Symptoms of allergic reaction include:

  • Skin rash
  • Hives
  • Itching
  • Blistering or lesions on the skin
  • Swelling of lips, tongue or throat
  • Tightening of the chest and airways
  • Wheezing
  • Severe nausea
  • Abdominal cramps
  • Vomiting or diarrhea
  • Seizure or convulsions
  • Severe dizziness or lightheadedness
  • Very weak, rapid pulse
  • Loss of consciousness

Dosage

The recommended starting dose of thioxanthene capsules or solution is either 2 mg three times each day, or 5 mg two times each day. The optimal dose is usually between 20 and 30 mg each day, but the dosage may be increased to a maximum of 60 mg each day. After 60 mg each day, there is no additional beneficial response to the drug. Due to the risk of tardive dyskinesia, the risk of which increases the longer the drug is used for, it's important to start with low dosages and increase only where necessary.

How to take thioxanthene

Oral thioxanthene solution should be should be diluted into a beverage or liquid, such as water, milk, fruit juice or soup. The drug is provided with a dropper which is clearly marked to ensure patients can administer the correct dosage. For the capsule form of the tablet, always swallow whole and do not chew, break or crush the capsules.

Thioxanthene should be consumed with either food or 8 ounces of milk or water to help minimize irritation of the stomach. It is usually recommended that it is taken with a main meal, not only to reduce irritation but to ensure that it is taken at roughly around the same times each day.

Never take more thioxanthene than is recommended by your doctor, as this could increase the risk of side effects or even lead to overdose. This is particularly important in teenagers, because the drug may have particularly strong effects in this age group.

If you miss a dose of thioxanthene, take it as soon as you remember unless it is almost time for your next dose. If this is the case, simply skip the missed dose and return to your original dosing schedule. Do not double doses of thioxanthene.

What to expect when taking thioxanthene

It usually takes several weeks for thioxanthene to reach its full effect. During the first few days you may notice some side effects. If they are not serious, they may gradually dissipate as your body adjusts to the medicine, but if they become prolonged you should mention them to your doctor.

When you stop taking thioxanthene, you may notice some physical withdrawal effects, particularly if you had been taking it in high dosages or for a long time. Doctors may recommend gradually tapering off the medicine to minimize the withdrawal effects. Always listen to your doctor's advice and do not suddenly stop taking the medicine without their approval, even if you feel as though you no longer need to take it.

Interactions

Thioxanthene is contraindicated in elderly patients for the management of dementia-related psychosis.

Thioxanthene could worsen the following conditions:

  • Blood disease
  • Heart, lung or blood vessel disease
  • Parkinson's disease
  • Stomach ulcers
  • Problems with urination
  • Enlarged prostate
  • Seizure disorders
  • Reye's syndrome (swelling of liver and brain)

In patients with liver disease, thioxanthene may not be filtered from the body as quickly as normal, which could result in higher levels of the drug entering the bloodstream. Effectively, this increases the dosage and increases the risk of harmful side effects. Patients with liver disease may require careful observation with taking thioxanthene and they may require lower dosages.

Drug interactions

Hepatic microsomal enzyme inducing agents, which affect that way the enzymes in the liver behave, can alter the effectiveness of thioxanthene. Examples of such drugs are:

  • Carbamazepine (Carbatrol, Epitol, Equetro, TEGretol)
  • Phenobarbitone
  • Flumazenil

Thioxanthene can heighten the effects of hypotensive agents (drugs which reduce blood pressure) and result in patients experiencing dangerously low blood pressure. Close observation is necessary in patients who are taking both hypotensive agents and thioxanthene.

The following medicines are not recommended for concurrent use with thioxanthene:

  • Amifampridine (Firdapse)
  • Bepridil (Vascor)
  • Bromopride
  • Cisapride (Propulsid)
  • Dronedarone (Multaq)
  • Mesoridazine (Serentil)
  • Metoclopramide (Metozolv ODT, Reglan)
  • Pimozide (Orap)
  • Piperaquine
  • Saquinavir (Invirase, Fortovase)
  • Sparfloxacin (Zagam)
  • Terfenadine (Seldane)
  • Thioridazine (Mellaril)
  • Ziprasidone (Geodon)

The following medicines are known to interact with thioxanthene, but they may still be prescribed with an adjusted dosage:

  • Alfentanil
  • Alfuzosin (Uroxatral)
  • Amiodarone (Cordarone, Pacerone)
  • Amisulpride
  • Amitriptyline (Vanatrip, Elavil, Endep)
  • Anagrelide (Agrylin)
  • Apomorphine (Apokyn, APO-Go, APO-Go Pen, Uprima)
  • Aripiprazole (Abilify, Abilify Discmelt)
  • Arsenic Trioxide (Trisenox)
  • Asenapine (Saphris, Saphris Black Cherry)
  • Astemizole (Hismanal)
  • Atazanavir (Reyataz)
  • Azithromycin (Zithromax)
  • Bedaquiline (Sirturo)
  • Buprenorphine (Probuphine)
  • Buserelin
  • Butorphanol (Stadol NS)
  • Chloroquine (Aralen Phosphate, Aralen Hydrochloride)
  • Chlorpromazine (Thorazine, Ormazine, Thorazine Spansule)
  • Ciprofloxacin (Cipro, Cipro XR, Proquin XR)
  • Citalopram (CeleXA)
  • Clarithromycin (Biaxin)
  • Clomipramine (Anafranil)
  • Clozapine (Clozaril, FazaClo, Versacloz, Clopine, CloZAPine Synthon, Denzapine, Zaponex)
  • Codeine
  • Crizotinib (Xalkori)
  • Cyclobenzaprine (Amrix, Comfort Pac with Cyclobenzaprine, Fexmid, Flexeril)
  • Dabrafenib (Tafinlar)
  • Dasatinib (Sprycel)
  • Degarelix (Firmagon)
  • Delamanid
  • Desipramine (Norpramin)
  • Deslorelin
  • Dihydrocodeine
  • Disopyramide (Norpace)
  • Dofetilide (Tikosyn)
  • Dolasetron (Anzemet)
  • Domperidone
  • Donepezil (Aricept)
  • Doxepin (Sinequan)
  • Droperidol (Inapsine)
  • Ebastine
  • Efavirenz (Sustiva)
  • Eribulin (Halaven)
  • Erythromycin (E.E.S. Granules, E.E.S.-400 Filmtab, EryPed, Ery-Tab, Erythrocin Stearate Filmtab, PCE Dispertab)
  • Escitalopram (Lexapro)
  • Famotidine (Heartburn Relief, Pepcid, Mylanta AR, Leader Acid Reducer)
  • Felbamate (Felbatol)
  • Fentanyl (Abstral, Actiq, Duragesic, Fentora, Ionsys, Lazanda, Sublimaze, Subsys)
  • Fingolimod (Gilenya)
  • Flecainide (Tambocor)
  • Fluconazole (Diflucan)
  • Fluoxetine (PROzac, Sarafem, Rapiflux, Selfemra)
  • Formoterol (Foradil Aerolizer, Perforomist)
  • Foscarnet (Foscavir)
  • Fosphenytoin (Cerebyx)
  • Galantamine (Razadyne, Reminyl)
  • Gatifloxacin (Zymaxid)
  • Gemifloxacin (Factive)
  • Gonadorelin
  • Goserelin (Zoladex)
  • Granisetron
  • Halofantrine
  • Haloperidol (Haldol)
  • Histrelin (Supprelin, Vantas)
  • Hydrocodone (Hysingla ER, Zohydro ER)
  • Hydromorphone (Dilaudid, Dilaudid-5, Exalgo)
  • Hydroquinidine
  • Hydroxychloroquine (Plaquenil, Quineprox)
  • Hydroxyzine (Atarax, Hyzine, Vistaject-50, Rezine, Vistacon, Vistacot, Vistaril, Vistazine)
  • Ibutilide (Corvert)
  • Iloperidone (Fanapt)
  • Imipramine (Tofranil)
  • Itraconazole (Onmel, Sporanox, Sporanox PulsePak)
  • Ivabradine (Corlanor)
  • Ketoconazole (Nizoral)
  • Lapatinib (Tykerb)
  • Leuprolide (Eligard, Lupron, Viadur)
  • Levofloxacin (Levaquin)
  • Lithium (Eskalith, Lithobid, Lithonate, Lithotabs)
  • Lumefantrine (Coartem)
  • Mefloquine (Mefloquine )
  • Meperidine (Demerol HCl)
  • Methadone (Dolophine, Methadose, Diskets)
  • Methotrimeprazine
  • Metronidazole (Flagyl)
  • Mifepristone (Korlym)
  • Milnacipran (Savella)
  • Mizolastine
  • Moricizine (Ethmozine)
  • Morphine (Arymo ER, Kadian, MorphaBond ER, MS Contin)
  • Moxifloxacin (Avelox)
  • Nafarelin (Synarel)
  • Nelfinavir (Viracept)
  • Nilotinib (Tasigna)
  • Norfloxacin (Noroxin)
  • Octreotide (SandoSTATIN)
  • Ofloxacin (Floxin)
  • Olanzapine (ZyPREXA)
  • Ondansetron (Zofran)
  • Oxycodone (Oxaydo, OxyCONTIN, Oxyfast, Roxicodone, Xtampza ER)
  • Oxymorphone (Opana, Numorphan)
  • Paliperidone (Invega)
  • Panobinostat (Farydak)
  • Papaverine
  • Paroxetine (Brisdelle, Paxil, Pexeva)
  • Pasireotide (Signifor)
  • Pazopanib (Votrient)
  • Pentamidine (Nebupent, Pentam 300)
  • Pentazocine (Talwin)
  • Perflutren Lipid Microsphere ()
  • Perphenazine (Definity, Optison)
  • Pipamperone
  • Posaconazole (Noxafil)
  • Probucol
  • Procainamide (Pronestyl, Procan SR, Procanbid)
  • Prochlorperazine (Compazine)
  • Promethazine (Phenergan)
  • Propafenone (Rythmol)
  • Protriptyline (Vivactil)
  • Quetiapine (SEROquel)
  • Quinidine (Quin-G, Cardioquin, Quinora, Quinidex Extentabs, Quinaglute Dura-Tabs, Quin-Release)
  • Quinine (Qualaquin, QM-260, Quinamm)
  • Ranolazine (Ranexa)
  • Remifentanil (Ultiva)
  • Risperidone (RisperDAL)
  • Ritonavir (Norvir)
  • Sertindole (Serdolect)
  • Sevoflurane (Sojourn, Ultane)
  • Sodium Phosphate
  • Sodium Phosphate, Dibasic
  • Sodium Phosphate, Monobasic
  • Solifenacin (VESIcare)
  • Sorafenib (NexAVAR)
  • Sotalol (Betapace, Sorine, Sotylize)
  • Sufentanil
  • Sunitinib (Sutent)
  • Tacrolimus (Astagraf XL, Envarsus XR, Hecoria, Prograf)
  • Tamoxifen (Soltamox)
  • Tapentadol (Nucynta)
  • Telaprevir (Incivek)
  • Telavancin (Vibativ)
  • Telithromycin (Ketek)
  • Tetrabenazine (Xenazine)
  • Tiotropium (Spiriva, Spiriva Respimat)
  • Tizanidine (Zanaflex)
  • Tolterodine (Detrol)
  • Toremifene (Fareston)
  • Tramadol (ConZip, Ultram)
  • Trazodone (Oleptro, Desyrel, Desyrel Dividose)
  • Trimipramine (Surmontil)
  • Triptorelin (Trelstar, Triptodur)
  • Vandetanib (Caprelsa)
  • Vardenafil (Levitra, Staxyn)
  • Vemurafenib (Zelboraf)
  • Venlafaxine (Effexor )
  • Vilanterol (Anoro Ellipta)
  • Vinflunine
  • Voriconazole (VFEND)
  • Vorinostat (Zolinza)
  • Zotepine

Warnings

There are many warnings associated with thioxanthene and antipsychotic medications in general. Make sure your doctor is aware of your full medical history when they prescribe the drug.

Risk of mortality in patients with dementia-related psychosis

Thioxanthene is not approved for treatment of psychosis in elderly patients with dementia. Research has found that the rate of mortality in dementia patients is elevated when antipsychotic medication like thioxanthene is administered. It is not fully understood why this is the case or how high the risk of mortality in these types of patients is, however it is much safer to avoid administering the drug in these instances.

History of hypersensitivity to thioxanthene or phenothiazine

Thioxanthene should not be administered to patients who have demonstrated a hypersensitivity to it in the past. It should also be used with caution in patients who have had a hypersensitive reaction to phenothiazine derivatives, which are also antipsychotics, since there could be cross sensitivity between these types of drugs.

Risk of tardive dyskinesia

Antipsychotic drugs like thioxanthene have been known to cause tardive dyskinesia, a potentially irreversible condition which causes involuntary movements such as grimacing and lip-smacking, rapid pursing or puckering of lips, tongue protrusion, blinking, rapid movements in legs, arms and fingers, resting tremors, rigidity, and unstable posture. The condition tends to be most common in elderly women who take thioxanthene, but the exact prevalence of the syndrome in those who take antipsychotics is unknown. It is believed that the longer an individual takes antipsychotic medicines, the higher the risk of tardive dyskinesia becomes.

Tardive dyskinesia may cease or become less severe once antipsychotic treatment is withdrawn. However, antipsychotics may partially suppress the symptoms of the condition which could make it more difficult to assess the progression or even identify the syndrome.

To minimize the risk of tardive dyskinesia, antipsychotics like thioxanthene should only be administered in the smallest doses necessary and for the shortest duration possible. In instances where chronic antipsychotic treatment is necessary, doctors often consider other treatment options where possible which don't pose the risk of the syndrome. In those who only respond successfully to antipsychotic medicines for chronic treatment for their condition, they should be assessed periodically for signs of tardive dyskinesia. If signs do occur, treatment with antipsychotics should be stopped unless the benefits of the drug outweigh far outweigh the problematic symptoms of tardive dyskinesia.

Risk of Neuroleptic Malignant Syndrome (NMS)

NMS is a potentially fatal condition which has been associated with the use of antipsychotic medicines such as thioxanthene. The syndrome causes hyperpyrexia (fever), altered mental state, muscle rigidity and instances of autonomic instability such as fast, slow or irregular heartbeat and irregular blood pressure. It isn't clear how common NMS is in those who take antipsychotic medicines, which makes it difficult to assess the risk of the condition occurring.

If NMS is identified in someone taking thioxanthene, the medicine should be discontinued immediately while NMS is treated. There is no definitive treatment for NMS other than treating its symptoms and complications as they arise. Once a patient recovers from NMS, they may be reintroduced to thioxanthene if necessary, but they should be closely monitored as it is possible for NMS to reoccur.

Use of thioxanthene during pregnancy and breastfeeding

There have not been adequate studies to fully assess the safety of thioxanthene during pregnancy. It is known that if the drug is administered during the third trimester, the baby risks experiencing withdrawal symptoms after delivery. This could lead to feeding disorder, respiratory distress, agitation, hypertonia or hypotonia (muscle rigidity or weakness), muscle tremors and somnolence (extreme sleepiness or drowsiness). The severity of these symptoms and the risk they pose to the baby can vary. For this reason, thioxanthene is only recommended for use during pregnancy if the benefits of the drug far outweigh the potential risk to the fetus.

It isn't known whether thioxanthene is excreted in breast milk, but similar antipsychotic medicines do, and they can pose health risks to nursing infants. Thioxanthene is therefore not recommended for nursing mothers. Instead, mothers should feed newborns on formula while taking thioxanthene.

Use of thioxanthene in children

The safety and efficacy of thioxanthene in children under 12 have not been established, so use of the drug in this age group is not recommended.

Driving, operating machinery

Thioxanthene acts on the central nervous system and can therefore affect normal mental and physical function, particularly during the first few days of taking the medicine. Avoid driving, operating machinery or performing other tasks which require alertness and physical competence, at least until you know how the drug affects you.

Alcohol and thioxanthene

Alcohol should be avoided while taking thioxanthene because it is also a central nervous system depressant and could worsen or increase the risk of harmful side effects such as hypotension (low blood pressure). Individuals with a history of alcohol abuse may not be prescribed thioxanthene.

Other precautions

In animal studies, thioxanthene was observed to have an antiemetic effect, which means that it reduces nausea and vomiting. For this reason, the drug may mask symptoms of overdose of toxic drugs, and obscure symptoms of serious conditions such as brain tumor or intestinal obstruction.

Thioxanthene and similar antipsychotic drugs can in rare cases lead to convulsions. Patients who are already at risk of convulsions due to medical history or due to alcohol withdrawal may have a lower convulsive threshold. If patients are undergoing anticonvulsive therapy, their dosage of these medications should remain the same if thioxanthene is to be administered at the same time.

Thioxanthene is a central nervous system depressant, and should be used with caution alongside other drugs of this nature. Careful adjustment of dosages may be necessary to minimize the risk of respiratory depression and other harmful side effects.

Antipsychotic drugs such as thioxanthene have been associated with elevated prolactin levels. A third of human breast cancers are dependent upon prolactin. In patients with a history of breast cancer, thioxanthene should be used with great caution.

Clinical trials have found that antipsychotic agents like thioxanthene could lead to leukopenia, which is white blood cell deficiency. The risk factor is higher for those who have pre-existing low white blood cell count (WBC) or who have experience drug-induced leukopenia in the past. In these patients, thioxanthene can still be prescribed but their complete blood count (CPC) should be monitored regularly, particularly during the first few months of treatment. Thioxanthene should be discontinued if WBC appears to decline.

Storage

Store thioxanthene in a cool, dry environment away from heat, direct light and moisture. Avoid storing them in the bathroom where they could be affected by increased heat and humidity.

Thioxanthene could be very harmful to children, pets and adults who have not been prescribed the medicine. Do not share the medicine with anyone else, and keep it in secure container with a childproof safety lid where possible. Store the medicine up and away from the ground so that it is not within easy reach of pets or children.

If you have any expired thioxanthene or leftover medicine that you no longer need, ask your healthcare provider how to safely dispose of it. Do not throw it in the trash or pour it down the drain or toilet.

Summary

Thioxanthenes are a group of medicines which treat mental and nervous conditions. Thioxanthene is usually prescribed to individuals with schizophrenia to treat psychosis, although it shouldn't be prescribed to elderly patients with dementia-related psychosis. It works by manipulating nerve pathways in the brain which are responsible for psychosis.

Dosages of thioxanthene usually begin at 2 mg three times each day, with most patients responding well to dosages of 20 to 30 mg in total each day. The maximum daily dosage of the drug is 60 mg; after this point, there are no more beneficial effects. Some people respond better to slightly higher individual doses taken less frequently than three times each day.

The drug is available in liquid, capsule, tablet and solution forms, and all should be taken with either food or an 8 ounce glass of milk or water to reduce irritation in the stomach. The solution form is designed to be diluted in liquid, such as water, juice, milk or soup, and is provided with a dropper which has measurements clearly marked upon it.

Common side effects of thioxanthene include drowsiness, dizziness, constipation, dry mouth and sensitivity to sunlight which might lead to skin rash or irritation, or more severe sunburn than usual. These are minor effects and don't usual require medical attention. More serious potential side effects include high fever, hypotension, seizures and breathing problems.

Thioxanthene is, like other antipsychotic drugs, associated with tardive dyskinesia, which is a syndrome which causes involuntary movements throughout the body, but particularly in the face, mouth, hands, arms and legs. Sometimes patients who develop tardive dyskinesia after taking thioxanthene see a reduction or discontinuation of the syndrome after they stop taking the drug. In others, the effects are permanent. The syndrome can occur after any length of time taking thioxanthene and at any dose, but it tends to be more common in those who take it over very long periods of time and at higher dosages. For this reason, thioxanthene should be given at the lowest dosages possible and for the shortest period of time possible.

Thioxanthene is a central nervous system (CNS) depressant and should be used with caution in patients who are also taking other CNS depressants, such as anti-anxiety medications or tranquilizers as it poses he risk of hypotension (low blood pressure) and other side effects. It is possible to continue taking both thioxanthene with other CNS depressants as long as the dosages of both are adjusted accordingly and the patient is monitored regularly. Alcohol should be avoided while thioxanthene is being taken, since it is also a CNS depressant.

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Last Reviewed:
December 23, 2017
Last Updated:
April 05, 2018
Content Source: