Clozapine
Risk Factor: M
Class: CENTRAL NERVOUS SYSTEM DRUGS
/ Tranquilizers
Contents of this page:
Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers
Fetal Risk Summary
Clozapine is an antipsychotic drug used in the treatment of schizophrenia. Reproduction studies in rats and rabbits at doses two to four times the human dose have found no evidence of impaired fertility or fetal harm (1,2).
A brief 1993 report described a woman who was treated prior to and throughout gestation with clozapine (dose not given) for treatment-resistant chronic undifferentiated schizophrenia (3). An apparently healthy, male, 8 lb 2 oz (about 3689 g) infant was delivered at term. The authors cited information on 14 other women who had taken clozapine during gestation apparently without fetal adverse effects (4).
Another Reference on the use of clozapine during pregnancy appeared in 1994 (5). A woman was maintained on 100 mg/day prior to and during the first 32 weeks of gestation. The dose was then lowered to 50 mg/day until she delivered a normal female infant at 41 weeks' gestation. No psychomotor abnormalities were observed up to 6 months of age. Clozapine plasma levels, measured in the mother throughout her pregnancy, ranged from 3855 ng/mL (100 mg/day) to 14.115.4 ng/mL (50 mg/day). At birth, the cord blood concentration was 27 ng/mL (maternal 14.1 ng/mL), representing a ratio of approximately 2. The amniotic fluid concentration was 11.6 ng/mL.
Nine diverse case reports of adverse pregnancy outcomes involving the use of clozapine during pregnancy have been reported to the FDA (F. Rosa, personal communication, FDA, 1995). In the absence of a cohort denominator, the cases do not suggest a fetal risk and may have been caused by chance. The cases were: Neonatal hypocalcemia, convulsions Asymmetry of buttock crease Turner's syndrome (chromosomal abnormality) Spontaneous abortion, hydropic villous degeneration (chromosomal abnormality) Spontaneous abortion 8th week (abnormal gestational sac) Multiple congenital defects (unspecified) (pregnancy terminated) Congenital blindness Clinodactyly thumbs and big toes Neonatal cerebral hemorrhage A case report in 1996 described an otherwise healthy male infant, exposed throughout gestation to clozapine (200300 mg/day) and lorazepam (7.512.5 mg/day), who developed transient, mild floppy infant syndrome after delivery at 37 weeks' gestation (6). The mother had taken the combination therapy for the treatment of schizophrenia. The hypotonia, attributed to lorazepam because of the absence of such reports in pregnancies exposed to clozapine alone, resolved 5 days after birth.
Breast Feeding Summary
Clozapine is concentrated in human breast milk (5). While taking clozapine 50 mg/day, a mother (described above) on her first postpartum day had a plasma concentration of 14.7 ng/mL and a concentration of 63.5 ng/mL from the first portion of her breast milk (milk:plasma ratio [M:P] 4.3). One week postpartum, 4 days after the dose was increased to 100 mg/day, the two concentrations were 41.4 and 115.6 ng/mL (M:P ratio 2.8), respectively. The infant was not allowed to breast-feed.
References
- Product information. Clozaril. Novartis Pharmaceuticals, 2000.
- Lindt S, Lauener E, Eichenberger E. The toxicology of 8-chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo[1,4]-diazepine (clozapine). Farmaco (Sci.) 1971;26:585602. As cited in Shepard TH.Catalog of Teratogenic Agents. 7th ed. Baltimore, MD:Johns Hopkins University Press, 1992:99.
- Walderman MD, Safferman AZ. Pregnancy and clozapine. Am J Psychiatry 1993;150:1689.
- Lieberman J, Safferman AZ. Clinical profile of clozapine: adverse reactions and agranulocytosis. In: Lapierre Y, Jones B, eds. Clozapine in Treatment Resistant Schizophrenia: A Scientific Update. London:Royal Society of Medicine, 1992. As cited in Walderman MD, Safferman AZ. Pregnancy and clozapine. Am J Psychiatry 1993;150:1689.
- Barnas C, Bergant A, Hummer M, Saria A, Fleischhacker WW. Clozapine concentrations in maternal and fetal plasma, amniotic fluid, and breast milk. Am J Psychiatry 1994;151:945.
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Di Michele V, Ramenghi LA, Sabatino G. Clozapine and lorazepam administration in pregnancy. Eur Psychiatry 1996;11:214.
Questions and Answers
Clozapine?, Anyone out there taking clozapine (or Clozaril)?
Side effects?
When they do weekly bloodwork, have you had your levels checked too?
Contact your doctor immediately if you experience unusual tiredness, weakness, fever, sore throat, sores in the mouth, or if you feel ill or as if you have the flu. These symptoms could be early signs of decreased white blood cell levels. A serious side effect from clozapine therapy is a decrease in white blood cells, which could lead to a life-threatening infection. You will need regular blood tests to monitor white blood cell levels during treatment
Stop taking clozapine and seek emergency medical attention if you experience any of the following other serious side effects:
an allergic reaction (difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives);
muscle stiffness;
uncontrollable movements of the mouth, tongue, jaw, face, arms, or legs;
fever;
an irregular or fast heartbeat;
fluttering in the chest;
chest pain or shortness of breath; or
liver problems.
Other, less serious side effects may be more likely to occur. Continue to take clozapine and talk to your doctor if you experience
dizziness or drowsiness,
nausea or upset stomach,
constipation,
salivation (watering mouth),
restlessness or agitation,
increased thirst or urination (may indicate increased blood sugar levels);
increased dreaming or nightmares.
Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome.
What other drugs will affect clozapine?
Clozapine may increase the side effects of other drugs that affect the central nervous system, including antidepressants, alcohol, antihistamines, sedatives (medicines that treat insomnia), pain relievers, anxiety medicines, muscle relaxants, and any others. Tell your doctor about all medicines that you are taking and do not take any medicine without first talking to your doctor.
Many drugs other than those listed here may also interact with clozapine possibly resulting in decreased effectiveness of the medication or dangerous side effects. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines, including herbal products, during treatment with clozapine.
What is the highest dosage of Clozapine a person can take daily?, What is the highest dosage a patient with schizophrenia can take? And what are the risks?
Patients are not given a high dose of Clozapine immediately, rather they are given gradually increasing dose starting from one-half of a 25-mg tablet (12.5 mg) once or twice daily and then be continued with daily dosage increments of 25-50 mg/day, if well tolerated, to achieve a target dose of 300-450 mg/day by the end of 2 weeks. Dosing should not exceed 900 mg/day.
You cannot do this without doctor's advise since dosage varies from one case to another, it's not like analgesics where you can either take 250mg or 500mg every 6 hours.
Taking Clozapine and its Side Effects?, I've tried 7 different anti-psychotic drugs and none of them have worked for me. After speaking to a CPN I have decided that Clozapine may be the drug for me, as it seems to work when all else has failed. However, I've heard it has some pretty heavy side effects and you have to have blood tests once a week for the first 18 weeks.
Can anyone tell me about their experience of this drug or tell me anything about it that might help my decision to take it?
Yes... clozaril can have some serious and not so serious side effects.. If you have any doubts, you should speak to your CPN again to give you ALL the info so you have an informed choice on your treatment.
One of the main side effects that most doctors worry about is "Neutropenia" This is when your white blood cell count is lowered to a level where you would be unable to fight infection and can become VERY ill with something like a common cold.
Blood samples are taken weekly for the first 18wks of treatment with a baseline sample taken before treatment starts. blood samples are then taken fortnightly until 52 weeks then monthly thereafter.
If your neurtophils are within normal limits..you get a "Green light" and it is ok to continue treatment.
An "Amber light" means you can continue treatment but with caution i.e. extra blood tests to monitor and a "Red light" means stop taking the treatment immediately.
Some other common side effects are:
hyper hydrosis, excessive salivation, increased blood pressure, elevated pulse, diarrhoea, enuresis, vomiting and nausea, sexual disfunction and weight gain.
If you do decide to start Clozaril, ask if "Kwells" can be prescribed along with it.
It is basically Hyocine Hydrobromide which is an anti emetic used for travel sickness. It drys up your secretions... so stops the excess salivation ( Some people salivate so much they are constantly drooling... not pleasant)
You'll start on a small dose of between 12.5mgs (1/2 tablet) and 25mgs ( 1 tablet) and it will be increased as long as your blood samples are showing green.
A therapeutic maintainance dose is usually around the 200 - 250mgs twice daily mark.
I've found it to be a very good form of medication for treatment resistant schizophrenia... If you have ALL the information, there is no reason why you can't take this medication and alliviate the side effects.
Good luck
will use of clozapine for long period cause harm to the person?, my friend is using one 25mg tab daily for the last 12 years.Recently he had a relapse of the mental disease and now he has to take 100 mg dose at least temporarily.Will it cause harm to his brain in any way?Will any medical person or persons using this medicine for years give me an answer?
Hello,
What is rather ironic about many of these drugs is, they really have not been out that long. This one has been out longer then some.
What 40 years is not that long....then these pills do different things to different people. So to say yes or no is just not to smart for even a experienced doctor in good faith to say.
Some people on these kinds of drugs do have relapses, it just what is. The body gets used to them or to much stress at certain times in peoples life's, change is a big stress factor for some people. Change in diet etc.. can all lead to these drugs just not working like the doctor thought they would.....
If the doctor is not taking blood work on a regular bases while on these drugs the question to ask is why not?
The mentally ill are very abused in the system. Anyone in the system for any amount of time can tell you there stories. If a person has no stories it is only because there problem has not been that long or it is not a serious problem as your friend has.
Just make sure tests get done on your friends internal organs. Make sure the drugs are not hurting anything.
Good luck, wish you well!
Why would a person with panic disorder be perscribed clozapine?, I do counseling
I'm not sure, but I think a lot of people on here are confusing Clozapine with Klonopin (generic name clonazepam, which is a benzo, anti-anxiety medication in the valium family.)
Clozapine is a strong and very effective medication, usually used as a "last resort" when many other medications have failed to work, with significant side effects (especially weight gain). From what I know it requires weekly blood tests.
just started on clozapine. why are they monitoring my blood pressure?, what i want to know is, can the clozaril make my BP go up or down?
Clozapine can make your blood pressure go up or down depending of course on you and your body. You also might be at risk for either high or low blood pressure because of age, height, weight etc. So your doctor as a precaution wants to monitor it.
