Clozapine (Oral Route) Precautions

Description and Brand Names

Drug information provided by: Merative, Micromedex®

US Brand Name

Clozaril
FazaClo
Versacloz

Descriptions

Clozapine is used to treat severely ill patients with schizophrenia who have used other medicines that did not work well. It is also used to lower risk of suicidal behavior in patients with schizophrenia or schizoaffective disorder. Clozapine changes some of the chemicals in the brain that are thought to cause schizophrenia. This medicine should not be used to treat behavioral problems in older adults with dementia.

This medicine is only available through a restricted program. You might be asked to read and sign papers that explain how the medicine works and some of the unwanted effects.

This product is available in the following dosage forms:

Tablet, Disintegrating
Tablet
Suspension

Before Using

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of clozapine in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of clozapine in the elderly. However, elderly patients are more likely to have constipation, trouble passing urine, uncontrolled movements, or age-related liver, kidney, or heart problems, which may require caution in patients receiving clozapine.

Breastfeeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Drug Interactions

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

Bepridil
Bromopride
Cisapride
Dronedarone
Droperidol
Fluconazole
Ketoconazole
Levoketoconazole
Mesoridazine
Metoclopramide
Nelfinavir
Pimozide
Piperaquine
Posaconazole
Potassium Citrate
Saquinavir
Sparfloxacin
Terfenadine
Thioridazine
Ziprasidone

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Abametapir
Abiraterone Acetate
Aclidinium
Adagrasib
Alfentanil
Alfuzosin
Alprazolam
Amantadine
Amiodarone
Amisulpride
Amitriptyline
Amoxapine
Amprenavir
Anagrelide
Apalutamide
Apomorphine
Aprepitant
Aripiprazole
Aripiprazole Lauroxil
Arsenic Trioxide
Asenapine
Astemizole
Atazanavir
Atropine
Azithromycin
Bedaquiline
Belladonna
Benzhydrocodone
Benztropine
Biperiden
Bromazepam
Brompheniramine
Buprenorphine
Bupropion
Buserelin
Buspirone
Butorphanol
Calcium Oxybate
Cannabidiol
Cannabis
Capmatinib
Carbamazepine
Carbinoxamine
Carisoprodol
Ceritinib
Cetirizine
Chloroquine
Chlorpheniramine
Chlorpromazine
Cimetidine
Cinacalcet
Ciprofloxacin
Citalopram
Clarithromycin
Clemastine
Clidinium
Clobazam
Clofazimine
Clomipramine
Clonazepam
Clothiapine
Clozapine
Cobicistat
Codeine
Conivaptan
Crizotinib
Cyclobenzaprine
Cyclopentolate
Cyclosporine
Cyproheptadine
Dabrafenib
Daridorexant
Darifenacin
Darunavir
Dasatinib
Degarelix
Delamanid
Delavirdine
Desipramine
Deslorelin
Deutetrabenazine
Dexmedetomidine
Dicyclomine
Dihydrocodeine
Diltiazem
Dimenhydrinate
Diphenhydramine
Disopyramide
Dofetilide
Dolasetron
Domperidone
Donepezil
Doxepin
Doxorubicin
Doxorubicin Hydrochloride Liposome
Doxylamine
Duloxetine
Ebastine
Efavirenz
Elagolix
Encorafenib
Enoxacin
Entrectinib
Enzalutamide
Eribulin
Erythromycin
Escitalopram
Esketamine
Etrasimod
Famotidine
Felbamate
Fentanyl
Fesoterodine
Fexinidazole
Fingolimod
Flavoxate
Flecainide
Flibanserin
Fluoxetine
Fluphenazine
Fluvoxamine
Formoterol
Fosamprenavir
Fosaprepitant
Foscarnet
Fosnetupitant
Fosphenytoin
Fostemsavir
Gabapentin
Gabapentin Enacarbil
Galantamine
Gatifloxacin
Gemifloxacin
Gepirone
Glasdegib
Glucagon
Glycopyrrolate
Glycopyrronium Tosylate
Gonadorelin
Goserelin
Granisetron
Halofantrine
Haloperidol
Histrelin
Homatropine
Hydrocodone
Hydromorphone
Hydroquinidine
Hydroxychloroquine
Hydroxyzine
Hyoscyamine
Ibutilide
Idelalisib
Iloperidone
Imatinib
Imipramine
Indinavir
Inotuzumab Ozogamicin
Interferon Alfa-2b
Ipratropium
Itraconazole
Ivabradine
Ivacaftor
Ivosidenib
Ketamine
Lacosamide
Lapatinib
Larotrectinib
Lefamulin
Lemborexant
Lenvatinib
Letermovir
LetibotulinumtoxinA-wlbg
Leuprolide
Levocetirizine
Levofloxacin
Levorphanol
Lithium
Lofexidine
Lomitapide
Lopinavir
Loxapine
Lumacaftor
Lumefantrine
Macimorelin
Magnesium Oxybate
Mate
Meclizine
Mefloquine
Mepenzolate
Meperidine
Methacholine
Methadone
Methotrimeprazine
Metronidazole
Mexiletine
Mibefradil
Mifepristone
Mirabegron
Mirtazapine
Mitotane
Mizolastine
Mobocertinib
Moclobemide
Moricizine
Morphine
Morphine Sulfate Liposome
Moxifloxacin
Nafarelin
Nalbuphine
Nefazodone
Netupitant
Nilotinib
Nirmatrelvir
Norfloxacin
Nortriptyline
Octreotide
Ofloxacin
Olanzapine
Oliceridine
Ondansetron
Orphenadrine
Osilodrostat
Osimertinib
Oxaliplatin
Oxitropium Bromide
Oxybutynin
Oxycodone
Oxymorphone
Ozanimod
Pacritinib
Palbociclib
Paliperidone
Panobinostat
Papaverine
Paroxetine
Pasireotide
Pazopanib
Peginterferon Alfa-2a
Pentamidine
Pentazocine
Periciazine
Perphenazine
Phenobarbital
Phenytoin
Pimavanserin
Pipamperone
Pipenzolate Bromide
Pirenzepine
Pitolisant
Pixantrone
Ponesimod
Potassium Oxybate
Pregabalin
Primidone
Probucol
Procainamide
Prochlorperazine
Procyclidine
Promethazine
Propafenone
Propantheline
Propiverine
Protriptyline
Quetiapine
Quinidine
Quinine
Quizartinib
Ranitidine
Ranolazine
Relugolix
Remifentanil
Remimazolam
Revefenacin
Ribociclib
Rifampin
Risperidone
Ritonavir
Rolapitant
Ropeginterferon Alfa-2b-njft
Scopolamine
Secretin Human
Selpercatinib
Sertindole
Sertraline
Sevoflurane
Siponimod
Sodium Oxybate
Sodium Phosphate
Sodium Phosphate, Dibasic
Sodium Phosphate, Monobasic
Solifenacin
Sorafenib
Sotalol
St John's Wort
Stramonium
Sufentanil
Sulpiride
Sultopride
Sunitinib
Tacrolimus
Tamoxifen
Tapentadol
Telaprevir
Telavancin
Telithromycin
Terbinafine
Terodiline
Tetrabenazine
Thiothixene
Tiotropium
Tizanidine
Tolterodine
Topiramate
Toremifene
Tramadol
Trazodone
Triclabendazole
Trifluoperazine
Trihexyphenidyl
Trimipramine
Triptorelin
Tropicamide
Trospium
Umeclidinium
Vandetanib
Vardenafil
Vemurafenib
Venlafaxine
Verapamil
Vilanterol
Viloxazine
Vinflunine
Voclosporin
Voriconazole
Vorinostat
Voxelotor
Zolpidem
Zotepine
Zuclopenthixol
Zuranolone

Other Interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

Grapefruit Juice
Tobacco

Using this medicine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

Caffeine

Proper Use

Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. Do not miss any doses.

This medicine comes with a patient instructions. Read and follow the instructions carefully. Ask your doctor if you have any questions.

Take the oral liquid or tablet with or without food.

If you are using the disintegrating tablet, make sure your hands are dry before you handle the tablet. Do not open the blister pack that contains the tablet until you are ready to take it. Remove the tablet from the blister pack by peeling back the foil, then taking the tablet out. Do not push the tablet through the foil. Place the tablet in your mouth. It should melt quickly. After the tablet has melted, swallow or chew it as desired.

Shake the bottle of the oral liquid for 10 seconds before each use. Measure the dose with the dosing syringe that comes with the package. Wash the oral syringe with warm water after using it.

Drink plenty of fluids with this medicine to help prevent constipation.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For oral dosage forms (disintegrating tablets, suspension, or tablets):
- For schizophrenia or prevention of suicidal behavior:
  - Adults—At first, 12.5 milligrams (mg) per day, taken as a single dose or 2 times per day. Your doctor may adjust your dose as needed. However, the dose is usually not more than 900 mg per day.
  - Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

If you miss 2 or more days of clozapine doses, talk to your doctor before you start taking it again. You might have to restart the medicine at a lower dose than you were taking before.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Do not refrigerate or freeze the oral liquid. Throw away any unused medicine 100 days after opening the bottle for the first time.

Precautions

Clozapine can cause some very serious blood problems that you will not be able to feel. Your doctor will check your blood at regular visits and it is important that you have your blood tests done when they are scheduled. The pharmacy will give you this medicine only if your blood tests show that it is safe for you to take it. Your doctor will make sure the medicine is working properly and change the dosage if needed.

Clozapine can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. If you can, avoid people with infections. Check with your doctor right away if you think you are getting an infection, or if you have a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.

Contact your doctor as soon as possible if you have chest pain or discomfort, a fast or slow heartbeat, trouble breathing, or fever and chills. These can be symptoms of a very serious problem with your heart.

Clozapine may cause drowsiness, blurred vision, convulsions (seizures), or to have trouble with thinking or controlling body movements, which may lead to falls, fractures or other injuries. Do not drive, operate machines, swimming, climbing, or do anything else that could be dangerous until you know how this medicine affects you.

This medicine can cause changes in your heart rhythm, such as a condition called QT prolongation. It may cause fainting or serious side effects in some patients. Contact your doctor right away if you have fast, pounding, or uneven heartbeats.

Dizziness, lightheadedness, or fainting may occur, especially when you get up from a lying or sitting position suddenly. These symptoms are more likely to occur when you begin taking this medicine, or when the dose is increased. Getting up slowly may help. If this problem continues or gets worse, check with your doctor.

Clozapine may cause stomach or bowel problems (eg, gastrointestinal hypomotility). Tell your doctor right away if you have severe constipation, nausea, vomiting, or stomach pain or swelling.

This medicine may increase your risk for anticholinergic effects, especially when used with other medicines (eg, benztropine, cyclobenzaprine, or diphenhydramine). Check with doctor right away if you have blurred vision, dizziness, drowsiness, confusion, delirium, or hallucinations, nausea, vomiting, constipation, difficult urination, eye pain, dry eyes, mouth, nose, or throat, flushing or redness of the face, troubled breathing, or fast heartbeat.

This medicine may cause serious skin reaction, including drug reaction with eosinophilia and systemic symptoms. Check with your doctor right away if you have black, tarry stools, chest pain, chills, cough, fever, painful or difficult urination, sore throat, sores, ulcers, or white spots in the mouth or on the lips, swollen glands, trouble breathing, unusual bleeding or bruising, or unusual tiredness or weakness.

For diabetic patients: This medicine may increase the amount of sugar in your blood. Check with your doctor right away if you have increased thirst or urination. Diabetic patients should check their blood and urine sugar levels more often than normal while taking this medicine.

In some patients, clozapine may cause increased watering of the mouth. Other patients, however, may get dryness of the mouth. For temporary relief of mouth dryness, use sugarless gum or candy, melt bits of ice in your mouth, or use a saliva substitute. However, if your mouth continues to feel dry for more than 2 weeks, check with your medical doctor or dentist. Continuing dryness of the mouth may increase the chance of dental disease, including tooth decay, gum disease, and fungus infections.

Check with your doctor right away if you are having convulsions (seizures), difficulty with breathing, fast heartbeat, high fever, high or low blood pressure, increased sweating, loss of bladder control, severe muscle stiffness, unusually pale skin, or tiredness. These could be symptoms of a serious condition called neuroleptic malignant syndrome (NMS).

This medicine may cause tardive dyskinesia (a movement disorder) among the elderly, especially elderly women. Check with your doctor right away if you have any of the following symptoms while taking this medicine: lip smacking or puckering, puffing of the cheeks, rapid or worm-like movements of the tongue, uncontrolled chewing movements, or uncontrolled movements of the arms and legs.

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, unusual tiredness or weakness, or yellow eyes or skin. These could be symptoms of a serious liver problem.

If you have been using this medicine regularly, do not stop taking it without first checking with your doctor. Your doctor may want you to gradually reduce the amount you are taking before stopping it completely. This is to help prevent the illness from suddenly returning and to decrease the chance of having symptoms such as headache, nausea, vomiting or diarrhea.

Check with your doctor right away if you have anxiety, chest pain, cough, dizziness or lightheadedness, fainting, fast heartbeat, pain, redness, or swelling in the arm or leg, or sudden trouble breathing. These maybe symptoms of serious blood clotting problems (eg, pulmonary embolism and deep vein thrombosis).

This medicine will add to the effects of alcohol and other central nervous system (CNS) depressants, which are medicines that slow down the nervous system and possibly cause drowsiness. Some examples of CNS depressants are antihistamines or medicine for hay fever, other allergies, or colds, sedatives, tranquilizers, or sleeping medicine, prescription pain medicine or narcotics, medicine for seizures or barbiturates, muscle relaxants, or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the above while you are using this medicine.

Make sure any doctor or dentist who treats you knows that you are using this medicine. You may need to stop using this medicine several days before having surgery or medical tests.

Tell your doctor if you smoke or drink products that contain caffeine.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (eg, St. John's wort) or vitamin supplements.

Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

Blurred vision
confusion
constipation
dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
fainting
fast, pounding, or irregular heartbeat or pulse
fever
nausea
shakiness in the legs, arms, hands, or feet
sleepiness or unusual drowsiness
sweating
trembling or shaking of the hands or feet
unusual tiredness or weakness
vomiting

Less common

Anxiety
black, tarry stools
chest pain or tightness
chills
cough or hoarseness
decrease in the frequency of urination
decrease in urine volume
difficult or labored breathing
difficulty in passing urine (dribbling)
discouragement
dry mouth
feeling sad or empty
fever with or without chills
frequent strong or increased urge to urinate
general feeling of tiredness or weakness
headache
hyperventilation
irritability
lack of appetite
loss of bladder control
loss of interest or pleasure
lower back or side pain
muscle spasm or jerking of the arms or legs
painful or difficult urination
pounding in the ears
restlessness or need to keep moving
seizures
severe or continuing headache
shakiness and unsteady walk
slurred speech
sore throat
sores, ulcers, or white spots on the lips or in the mouth
sudden jerky movements of the body
sudden loss of consciousness
swollen glands
throat discomfort
trouble concentrating
trouble sleeping
unsteadiness, trembling, or other problems with muscle control or coordination

Rare

Absence of or decrease in movement
change in appetite
dark urine
decreased sexual ability
difficult or fast breathing or sudden shortness of breath
increased sweating
increased thirst
increased urination
lip smacking or puckering
muscle stiffness (severe)
puffing of the cheeks
rapid or worm-like movements of the tongue
swelling or pain in the leg
uncontrolled chewing movements
uncontrolled movements of the arms and legs
unusual bleeding or bruising
unusually pale skin
weakness
yellow eyes or skin

Incidence not known

Bloating
burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
clay-colored stools
confusion as to time, place, or person
diarrhea
epileptic seizure that will not stop
feeling that others are watching you or controlling your behavior
feeling that others can hear your thoughts
feeling, seeing, or hearing things that are not there
holding false beliefs that cannot be changed by fact
inability to move the eyes
increased blinking or spasms of the eyelid
indigestion
itching or skin rash
joint pain
light-colored stools
muscle twitching
pains in the stomach, side, or abdomen, possibly radiating to the back
rhythmic movement of the muscles
severe mood or mental changes
sticking out of the tongue
swelling around the eyes
swelling of the body or feet and ankles
trouble with speaking
unpleasant breath odor
unusual behavior
unusual excitement, nervousness, or restlessness
unusual facial expressions
unusual weight gain
upper right abdominal or stomach pain
vomiting of blood

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Acid or sour stomach
belching
feeling of constant movement of self or surroundings
heartburn
relaxed and calm sensation of spinning
sleepiness

Less common

Blurred or loss of vision
change or problem with discharge of semen
disturbed color perception
double vision
halos around lights
inability to sit still
increase in body movements
muscle ache or pain
muscle weakness
night blindness
nightmares
overbright appearance of lights
pain in the back, neck, or legs
pain in the chest below the breastbone
severe muscle stiffness
sore tongue
stuffy nose
tunnel vision
unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness

Incidence not known

Blistering, peeling, or loosening of the skin
hives, sores, welting, or blisters
increased sensitivity of the skin to sunlight
painful or prolonged erection of the penis
red skin lesions, often with a purple center
red, irritated eyes
reddening of the skin, especially around the ears
severe stomach pain
severe sunburn
swelling of the eyes, face, or inside of the nose
swelling of the salivary glands

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Portions of this document last updated: April 01, 2024

Original article: https://www.mayoclinic.org/drugs-supplements/clozapine-oral-route/precautions/drg-20066859

Clozapine (Oral Route)

Description and Brand Names

US Brand Name

Descriptions

Before Using

Allergies

Pediatric

Geriatric

Breastfeeding

Drug Interactions

Other Interactions

Other Medical Problems

Proper Use

Dosing

Missed Dose

Storage

Precautions

Side Effects

More common

Less common

Rare

Incidence not known

More common

Less common

Incidence not known

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