Clozapine interactions

Food & lifestyle

• alcohol

  Moderate

  Synergy

  Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

  What to do: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

  4 sources

  1. Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc. (1990):
  3. "Product Information. Fycompa (perampanel)." Eisai Inc (2012):
  4. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):

Conditions

Conditions in which Clozapine needs care, as documented in this source.

• Agranulocytosis

  Major

  The use of clozapine is contraindicated in patients with myeloproliferative disorders, preexisting bone marrow depression, or a history of clozapine-induced agranulocytosis or severe granulocytopenia. Clozapine therapy is associated with the development of agranulocytosis, defined as an absolute neutrophil count (ANC) below 500/mm3. The cumulative incidence is estimated at 1% to 2% after one year of use. The onset is generally between 4 to 16 weeks following initiation of therapy, and it is usually reversible if detected early and the drug discontinued promptly. All patients should have a white blood cell (WBC) count prior to initiating therapy, and clozapine should not be administered if baseline WBC count is less than 3500/mm3. WBC counts and differential should be monitored closely during therapy and for 4 weeks after end of therapy according to product labeling. Also, patients should be advised to immediately report signs of infection such as fever, sore throat, malaise, lethargy, and flu-like symptoms. Individuals who develop clozapine-induced agranulocytosis or severe granulocytopenia (WBC count < 2000/mm3 or ANC < 1000/mm3) should not be rechallenged following recovery, since the condition may recur, often with a shorter latency on reexposure. If continued neuroleptic therapy is necessary, other agents may be used with little apparent risk of cross-sensitivity.

  21 sources

  1. Safferman AZ, Lieberman JA, Alvir JMJ, Howard A "Rechallenge in clozapine-induced agranulocytosis." Lancet 339 (1992): 1296-7
  2. Joseph G, Nguyen V, Smith JD "HLA-B38 and clozapine-induced agranulocytosis." Ann Intern Med 116 (1992): 605
  3. Cates M, Lusk K, Wells BG, Guthrie TC "Nonleukopenic neutropenia in a patient treated with clozapine." N Engl J Med 326 (1992): 840-1
  4. Pisciotta AV, Konings SA, Ciesemier LL, Cronkite CE, Lieberman JA "Cytotoxic activity in serum of patients with clozapine-induced agranulocytosis." J Lab Clin Med 119 (1992): 254-66
  5. Hummer M, Kurz M, Barnas C, Fleischhacker WW "Transient neutropenia induced by clozapine." Psychopharmacol Bull 28 (1992): 287-90
  6. Tueth M "Side effects of clozipine (Clozaril) requiring emergency treatment." Am J Emerg Med 11 (1993): 312-3
  7. Lieberman JA, Yunis J, Egea E, Canoso RT, Kane JM, Yunis EJ "HLA-B38, DR4, DQw3 and clozapine-induced agranulocytosis in Jewish patients with schizophrenia." Arch Gen Psychiatry 47 (1990): 945-8
  8. Weide R, Koppler H, Heymanns J, Pfluger KH, Havemann K "Successful treatment of clozapine induced agranulocytosis with granulocyte-colony stimulating factor (G-CSF)." Br J Haematol 80 (1992): 557-9

  Show all 21 sourcesShow fewer sources

  9. Gerson SL "Clozapine--deciphering the risks.." N Engl J Med 329 (1993): 204-5
  10. Alvir JM, Lieberman JA, Safferman AZ, Schwimmer JL, Schaaf JA "Clozapine-induced agranulocytosis. Incidence and risk factors in the United States." N Engl J Med 329 (1993): 162-7
  11. Amsler HA, Teerenhovi L, Barth E, Harjula K, Vuopio P "Agranulocytosis in patients treated with clozapine. A study of the Finnish epidemic." Acta Psychiatr Scand 56 (1977): 241-8
  12. Peck CC "FDA's position on the clozaril patient management system." Hosp Community Psychiatry 41 (1990): 876-7
  13. Lieberman JA, Safferman AZ "Clinical profile of clozapine: adverse reactions and agranulocytosis." Psychiatr Q 63 (1992): 51-70
  14. Gerson SL, Guillion G, Hong-Shen Y, Masor C "Granulocyte colony-stimulating factor for clozapine-induced agranulocytosis." Lancet 340 (1992): 1097
  15. "Product Information. Clozaril (clozapine)." Novartis Pharmaceuticals (2001):
  16. Nielsen H "Recombinant human granulocyte colony-stimulating factor (rhg-csf filgrastim) treatment of clozapine-induced agranulocytosis." J Intern Med 234 (1993): 529-31
  17. Gerson SL, Arce C, Meltzer HY "N-desmethylclozapine - a clozapine metabolite that suppresses haemopoiesis." Br J Haematol 86 (1994): 555-61
  18. Clozapine Study Group "The safety and efficacy of clozapine in severe treatment-resistant schizophrenia patients in the UK." Br J Psychiatry 163 (1993): 150-4
  19. Raison CL, Guze BH, Kissell RL "Successful treatment of clozapine-induced agranulocytosis with granulocyte colony-stimulating factor." J Clin Psychopharmacol 14 (1994): 285-6
  20. Gerson SL "G-CSF and the management of clozapine-induced agranulocytosis." J Clin Psychiatry 55 (1994): 139-42
  21. Gullion G, Yeh HS "Treatment of clozapine-induced agranulocytosis with recombinant granulocyte colony-stimulating factor." J Clin Psychiatry 55 (1994): 401-5

• Alcoholic Intoxication

  Major

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

  10 sources

  1. "Product Information. Haldol (haloperidol)." McNeil Pharmaceutical (2002):
  2. "Product Information. Navane (thiothixene)." Roerig Division (2001):
  3. "Product Information. Clozaril (clozapine)." Novartis Pharmaceuticals (2001):
  4. "Product Information. Risperdal (risperidone)." Janssen Pharmaceuticals (2001):
  5. "Product Information. Zyprexa (olanzapine)." Lilly, Eli and Company (2001):
  6. "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals (2001):
  7. "Product Information. Moban (molindone)." Gate Pharmaceuticals (2001):
  8. "Product Information. Orap (pimozide)." Gate Pharmaceuticals

  Show all 10 sourcesShow fewer sources

  9. "Product Information. Geodon (ziprasidone)." Pfizer U.S. Pharmaceuticals (2001):
  10. "Product Information. Loxitane C (loxapine)." Apothecon Inc (2022):

• Anticholinergic Syndrome

  Major

  Neuroleptic agents have anticholinergic activity, to which elderly patients are particularly sensitive. Clozapine and low-potency agents such as chlorpromazine and thioridazine tend to exhibit greater anticholinergic effects than other agents in the class. Clozapine use has been associated with impairment of intestinal peristalsis ranging from constipation to intestinal obstruction, fecal impaction, and paralytic ileus. Therapy with neuroleptic agents should be administered cautiously in patients with preexisting conditions that are likely to be exacerbated by anticholinergic activity, such as urinary retention or obstruction; angle-closure glaucoma, untreated intraocular hypertension, or uncontrolled primary open-angle glaucoma; and gastrointestinal obstructive disorders.

  6 sources

  1. Grohmann R, Ruther E, Sassim N, Schmidt LG "Adverse effects of clozapine." Psychopharmacology (Berl) 99 (1989): s101-4
  2. Tueth M "Side effects of clozipine (Clozaril) requiring emergency treatment." Am J Emerg Med 11 (1993): 312-3
  3. "Product Information. Clozaril (clozapine)." Novartis Pharmaceuticals (2001):
  4. Marinkovic D, Timotijevic I, Babinski T, Totic S, Paunovic VR "The side-effects of clozapine: a four year follow-up study." Prog Neuropsychopharmacol Biol Psychiatry 18 (1994): 537-44
  5. Cohen MAA, Alfonso CA, Mosquera M "Development of urinary retention during treatment with clozapine and meclizine." Am J Psychiatry 151 (1994): 619-20
  6. Talbert RL, Yee GC, DiPiro JT, Matzke GR, Posey LM, Wells BG "Pharmacotherapy: A Pathophysiologic Approach" Stamford, CT: Appleton & Lange (1999):

• Dementia

  Major

  Older patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death; although the causes were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. A causal relationship with antipsychotic use has not been established. In controlled trials in older patients with dementia-related psychosis, patients randomized to risperidone, aripiprazole, and olanzapine had higher incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, compared to patients treated with placebo. These agents are not approved for the treatment of patients with dementia-related psychosis.

  14 sources

  1. "Product Information. Clozaril (clozapine)." Novartis Pharmaceuticals (2001):
  2. "Product Information. Risperdal (risperidone)." Janssen Pharmaceuticals (2001):
  3. "Product Information. Zyprexa (olanzapine)." Lilly, Eli and Company (2001):
  4. "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals (2001):
  5. "Product Information. Geodon (ziprasidone)." Pfizer U.S. Pharmaceuticals (2001):
  6. "Product Information. Abilify (aripiprazole)." Bristol-Myers Squibb (2002):
  7. "Product Information. Invega (paliperidone)." Janssen Pharmaceuticals (2007):
  8. "Product Information. Fanapt (iloperidone)." Vanda Pharmaceuticals Inc (2009):

  Show all 14 sourcesShow fewer sources

  9. "Product Information. Saphris (asenapine)." Schering-Plough Corporation (2009):
  10. "Product Information. Latuda (lurasidone)." Sunovion Pharmaceuticals Inc (2010):
  11. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
  12. "Product Information. Vraylar (cariprazine)." Actavis Pharma, Inc. (2015):
  13. "Product Information. Nuplazid (pimavanserin)." Accelis Pharma (2016):
  14. "Product Information. Caplyta (lumateperone)." Intra-Cellular Therapies, Inc. (2022):

• Hepatitis

  Major

  Hepatitis has been reported in association with the use of clozapine, both in patients with and without underlying liver function abnormalities. Therapy with clozapine should be administered cautiously in patients with preexisting liver disease. The drug should be discontinued if clinically significant elevations of liver function tests or symptoms of jaundice occur.

  4 sources

  1. Grohmann R, Ruther E, Sassim N, Schmidt LG "Adverse effects of clozapine." Psychopharmacology (Berl) 99 (1989): s101-4
  2. Kellner M, Wiedemann K, Krieg JC, Berg PA "Toxic hepatitis by clozapine treatment." Am J Psychiatry 150 (1993): 985-6
  3. "Product Information. Clozaril (clozapine)." Novartis Pharmaceuticals (2001):
  4. Marinkovic D, Timotijevic I, Babinski T, Totic S, Paunovic VR "The side-effects of clozapine: a four year follow-up study." Prog Neuropsychopharmacol Biol Psychiatry 18 (1994): 537-44

• Neuroleptic Malignant Syndrome

  Major

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

  46 sources

  1. Hermesh H, Sirota P, Eviatar J "Recurrent neuroleptic malignant syndrome due to haloperidol and amantadine." Biol Psychiatry 25 (1989): 962-5
  2. Ryken TC, Merrell AN "Haloperidol-induced neuroleptic malignant syndrome in a 67-year-old woman with parkinsonism." West J Med 151 (1989): 326-8
  3. Levitt AJ, Midha R, Craven JL "Neuroleptic malignant syndrome with intravenous haloperidol." Can J Psychiatry 35 (1990): 789
  4. Aisen PS, Lawlor BA "Neuroleptic malignant syndrome induced by low-dose haloperidol." Am J Psychiatry 149 (1992): 844
  5. Caroff SN "The neuroleptic malignant syndrome." J Clin Psychiatry 41 (1980): 79-83
  6. "Product Information. Haldol (haloperidol)." McNeil Pharmaceutical (2002):
  7. "Product Information. Navane (thiothixene)." Roerig Division (2001):
  8. Miller DD, Sharafuddin MJ, Kathol RG "A case of clozapine-induced neuroleptic malignant syndrome." J Clin Psychiatry 52 (1991): 99-101

  Show all 46 sourcesShow fewer sources

  9. DasGupta K, Young A "Clozapine-induced neuroleptic malignant syndrome." J Clin Psychiatry 52 (1991): 105-7
  10. Anderson ES, Powers PS "Neuroleptic malignant syndrome associated with clozapine use." J Clin Psychiatry 52 (1991): 102-4
  11. "Product Information. Clozaril (clozapine)." Novartis Pharmaceuticals (2001):
  12. "Product Information. Risperdal (risperidone)." Janssen Pharmaceuticals (2001):
  13. Nemecek D "Atropism may precipitate neuroleptic malignant syndrome during treatment with clozapine." Am J Psychiatry 150 (1993): 1561
  14. Ewert AL, Kloek J, Wells B, Phelps S "Neuroleptic malignant syndrome associated with loxapine" J Clin Psychiatry 44 (1983): 37-8
  15. Chong LS, Abbott PM "Neuroleptic malignant syndrome secondary to loxapine." Br J Psychiatry 159 (1991): 572-3
  16. Padgett R, Lipman E "Use of neuroleptics after an episode of neuroleptic malignant syndrome" Can J Psychiatry 34 (1989): 323-5
  17. Webster P, Wijeratne C "Risperidone-induced neuroleptic malignant syndrome." Lancet 344 (1994): 1228-9
  18. Campellone JV, Mccluskey LF, Greenspan D "Fatal outcome from neuroleptic malignant syndrome associated with clozapine." Neuropsychiatry Neuropsychol Behav Neurol 8 (1995): 70-3
  19. Raitasuo V, Vataja R, Elomaa E "Risperidone-induced neuroleptic malignant syndrome in young patient." Lancet 344 (1994): 1705
  20. Dave M "Two cases of risperidone-induced neuroleptic malignant syndrome." Am J Psychiatry 152 (1995): 1233-4
  21. Singer S, Richards C, Boland RJ "Two cases of risperidone-induced neuroleptic malignant syndrome." Am J Psychiatry 152 (1995): 1234
  22. Najara JE, Enikeev ID "Risperidone and neuroleptic malignant syndrome: a case report." J Clin Psychiatry 56 (1995): 534-5
  23. Tarsy D "Risperidone and neuroleptic malignant syndrome." JAMA 275 (1996): 446
  24. Kern JL, Cernek PK "Delayed risperidone-induced malignant syndrome." Ann Pharmacother 30 (1996): 300
  25. Sharma R, Trappler B, Ng YK, Leeman CP "Risperidone-induced neutroleptic malignant syndrome." Ann Pharmacother 30 (1996): 775-8
  26. "Product Information. Zyprexa (olanzapine)." Lilly, Eli and Company (2001):
  27. Gleason PP, Conigliaro RL "Neuroleptic malignant syndrome with risperidone." Pharmacotherapy 17 (1997): 617-21
  28. "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals (2001):
  29. "Product Information. Moban (molindone)." Gate Pharmaceuticals (2001):
  30. "Product Information. Orap (pimozide)." Gate Pharmaceuticals
  31. Moltz DA, Coeytaux RR "Case report: Possible neuroleptic malignant syndrome associated with olanzapine." J Clin Psychopharmacol 18 (1998): 485-6
  32. Burkhard PR, Vingerhoets FJG "Olanzapine induced neuroleptic malignant syndrome." Arch Gen Psychiat 56 (1999): 101-2
  33. Johnson V, Bruxner G "Neuroleptic malignant syndrome associated with olanzapine." Aust N Z J Psychiat 32 (1998): 884-6
  34. Margolese HC, Chouinard G "Olanzapine-induced neuroleptic malignant syndrome with mental retardation." Am J Psychiat 156 (1999): 1115-6
  35. Levenson JL "Neuroleptic malignant syndrome after the initiation of olanzapine." J Clin Psychopharmacol 19 (1999): 477-8
  36. Nyfort-Hansen K, Alderman CP "Possible neuroleptic malignant syndrome associated with olanzapine." Ann Pharmacother 34 (2000): 667
  37. SierraBiddle D, Herran A, DiezAja S, GonzalezMata JM, Vidal E, DiezManrique F, VazquezBarquero JL "Neuroleptic malignant syndrome and olanzapine." J Clin Psychopharmacol 20 (2000): 704-5
  38. "Product Information. Geodon (ziprasidone)." Pfizer U.S. Pharmaceuticals (2001):
  39. "Product Information. Loxitane C (loxapine)." Apothecon Inc (2022):
  40. "Product Information. Abilify (aripiprazole)." Bristol-Myers Squibb (2002):
  41. "Product Information. Invega (paliperidone)." Janssen Pharmaceuticals (2007):
  42. "Product Information. Fanapt (iloperidone)." Vanda Pharmaceuticals Inc (2009):
  43. "Product Information. Saphris (asenapine)." Schering-Plough Corporation (2009):
  44. "Product Information. Latuda (lurasidone)." Sunovion Pharmaceuticals Inc (2010):
  45. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
  46. "Product Information. Vraylar (cariprazine)." Actavis Pharma, Inc. (2015):

• Respiratory Insufficiency

  Major

  The use of neuroleptic agents is contraindicated in comatose patients and patients with severe central nervous system depression. Neuroleptic agents may potentiate the CNS and respiratory depression in these patients.

  7 sources

  1. "Product Information. Haldol (haloperidol)." McNeil Pharmaceutical (2002):
  2. "Product Information. Navane (thiothixene)." Roerig Division (2001):
  3. Vetter PH, Proppe DG "Clozapine-induced coma." J Nerv Ment Dis 180 (1992): 58-9
  4. "Product Information. Clozaril (clozapine)." Novartis Pharmaceuticals (2001):
  5. "Product Information. Moban (molindone)." Gate Pharmaceuticals (2001):
  6. "Product Information. Orap (pimozide)." Gate Pharmaceuticals
  7. "Product Information. Loxitane C (loxapine)." Apothecon Inc (2022):

• Dyslipidemias

  Moderate

  Atypical antipsychotic drugs have been associated with undesirable alterations in lipid levels. While all agents in the class have been shown to produce some changes, each drug has its own specific risk profile. Before or soon after initiation of antipsychotic medications, a fasting lipid profile should be obtained at baseline and monitored periodically during treatment.

  13 sources

  1. "Product Information. Clozaril (clozapine)." Novartis Pharmaceuticals (2001):
  2. "Product Information. Risperdal (risperidone)." Janssen Pharmaceuticals (2001):
  3. "Product Information. Zyprexa (olanzapine)." Lilly, Eli and Company (2001):
  4. "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals (2001):
  5. "Product Information. Geodon (ziprasidone)." Pfizer U.S. Pharmaceuticals (2001):
  6. "Product Information. Abilify (aripiprazole)." Bristol-Myers Squibb (2002):
  7. "Product Information. Invega (paliperidone)." Janssen Pharmaceuticals (2007):
  8. "Product Information. Fanapt (iloperidone)." Vanda Pharmaceuticals Inc (2009):

  Show all 13 sourcesShow fewer sources

  9. "Product Information. Saphris (asenapine)." Schering-Plough Corporation (2009):
  10. "Product Information. Latuda (lurasidone)." Sunovion Pharmaceuticals Inc (2010):
  11. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
  12. "Product Information. Vraylar (cariprazine)." Actavis Pharma, Inc. (2015):
  13. "Product Information. Caplyta (lumateperone)." Intra-Cellular Therapies, Inc. (2022):

• Hyperglycemia

  Moderate

  Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported with the use of atypical antipsychotic agents. Patients with diabetes should be monitored for worsening control of blood glucose when treated with these agents. It is recommended that patients with risk factors for diabetes mellitus starting treatment with atypical antipsychotics should undergo fasting blood glucose testing at the beginning of treatment, and periodically thereafter. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when treatment with these agents was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the atypical antipsychotic drug.

  13 sources

  1. "Product Information. Clozaril (clozapine)." Novartis Pharmaceuticals (2001):
  2. "Product Information. Risperdal (risperidone)." Janssen Pharmaceuticals (2001):
  3. "Product Information. Zyprexa (olanzapine)." Lilly, Eli and Company (2001):
  4. "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals (2001):
  5. "Product Information. Geodon (ziprasidone)." Pfizer U.S. Pharmaceuticals (2001):
  6. "Product Information. Abilify (aripiprazole)." Bristol-Myers Squibb (2002):
  7. "Product Information. Invega (paliperidone)." Janssen Pharmaceuticals (2007):
  8. "Product Information. Fanapt (iloperidone)." Vanda Pharmaceuticals Inc (2009):

  Show all 13 sourcesShow fewer sources

  9. "Product Information. Saphris (asenapine)." Schering-Plough Corporation (2009):
  10. "Product Information. Latuda (lurasidone)." Sunovion Pharmaceuticals Inc (2010):
  11. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
  12. "Product Information. Vraylar (cariprazine)." Actavis Pharma, Inc. (2015):
  13. "Product Information. Caplyta (lumateperone)." Intra-Cellular Therapies, Inc. (2022):

• Hyperglycemia

  Moderate

  Severe hyperglycemia, sometimes resulting in ketoacidosis, has been reported during clozapine treatment in patients with no prior history of hyperglycemia. Glucose levels normalized in most cases following discontinuation of clozapine, and a rechallenge in one patient produced a recurrence of hyperglycemia. While a causal relationship has not been established, patients with or predisposed to hyperglycemia should be monitored during clozapine therapy. Dosage adjustments in insulin or oral hypoglycemic medications may be necessary in patients with diabetes.

  2 sources

  1. "Product Information. Clozaril (clozapine)." Novartis Pharmaceuticals (2001):
  2. Wehring H, Alexander B, Perry PJ "Diabetes mellitus associated with clozapine therapy." Pharmacotherapy 20 (2000): 844-7

• Hyperprolactinemia

  Moderate

  The chronic use of neuroleptic agents can cause persistent elevations in prolactin levels due to antagonism of dopamine D2 receptors. Based on in vitro data, approximately one-third of human breast cancers are thought to be prolactin-dependent. The clinical significance of this observation with respect to long-term neuroleptic therapy is unknown. Chronic administration of neuroleptic drugs has been associated with mammary tumorigenesis in rodent studies but not in human clinical or epidemiologic studies. Until further data are available, therapy with neuroleptic agents should be administered cautiously in patients with a previously detected breast cancer. Caution is also advised in patients with preexisting hyperprolactinemia. Hyperprolactinemia may suppress hypothalamic gonadotrophin releasing hormone (GnRH), resulting in reduced pituitary gonadotropin secretion. This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds; however, the clinical significance of elevated serum prolactin levels is unknown for most patients. Long-standing hyperprolactinemia when associated with hypogonadism may lead to decreased bone density in both female and male patients.

  16 sources

  1. Meco G, Falaschi P, Casacchia M, et al. "Neuroendocrine effects of haloperidol decanoate in patients with chronic schizophrenia." Adv Biochem Psychopharmacol 40 (1985): 89-93
  2. Ash PR, Bouma D "Exaggerated hyperprolactinemia in response to thiothixene ." Arch Neurol 38 (1981): 534-5
  3. "Product Information. Haldol (haloperidol)." McNeil Pharmaceutical (2002):
  4. "Product Information. Navane (thiothixene)." Roerig Division (2001):
  5. Huang ML, Van Peer A, Woestenborghs R, De Coster R, Heykants J, Jansen AA, Zylicz Z, Visscher HW, Jonkman JH "Pharmacokinetics of the novel antipsychotic agent risperidone and the prolactin response in healthy subjects." Clin Pharmacol Ther 54 (1993): 257-68
  6. "Product Information. Clozaril (clozapine)." Novartis Pharmaceuticals (2001):
  7. "Product Information. Risperdal (risperidone)." Janssen Pharmaceuticals (2001):
  8. "Product Information. Compazine (prochlorperazine)." SmithKline Beecham (2001):

  Show all 16 sourcesShow fewer sources

  9. Dickson RA, Dalby JT, Williams R, Edwards AL "Risperidone-induced prolactin elevations in premenopausal women with schizophrenia." Am J Psychiatry 152 (1995): 1102-3
  10. "Product Information. Zyprexa (olanzapine)." Lilly, Eli and Company (2001):
  11. "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals (2001):
  12. "Product Information. Moban (molindone)." Gate Pharmaceuticals (2001):
  13. "Product Information. Orap (pimozide)." Gate Pharmaceuticals
  14. "Product Information. Geodon (ziprasidone)." Pfizer U.S. Pharmaceuticals (2001):
  15. "Product Information. Loxitane C (loxapine)." Apothecon Inc (2022):
  16. Bai YM, Ciu HJ, Guo ZZ "Risperidone-induced hyperprolactinemia in an elderly woman." Am J Psychiatry 159 (2002): 2112

• Hypotension

  Moderate

  The use of atypical antipsychotic agents has been associated with orthostatic hypotension and syncope. Therapy with atypical antipsychotics should be administered cautiously in patients with hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with atypical antipsychotics. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.

  13 sources

  1. "Product Information. Clozaril (clozapine)." Novartis Pharmaceuticals (2001):
  2. "Product Information. Risperdal (risperidone)." Janssen Pharmaceuticals (2001):
  3. "Product Information. Zyprexa (olanzapine)." Lilly, Eli and Company (2001):
  4. "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals (2001):
  5. "Product Information. Geodon (ziprasidone)." Pfizer U.S. Pharmaceuticals (2001):
  6. "Product Information. Abilify (aripiprazole)." Bristol-Myers Squibb (2002):
  7. "Product Information. Invega (paliperidone)." Janssen Pharmaceuticals (2007):
  8. "Product Information. Fanapt (iloperidone)." Vanda Pharmaceuticals Inc (2009):

  Show all 13 sourcesShow fewer sources

  9. "Product Information. Saphris (asenapine)." Schering-Plough Corporation (2009):
  10. "Product Information. Latuda (lurasidone)." Sunovion Pharmaceuticals Inc (2010):
  11. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
  12. "Product Information. Vraylar (cariprazine)." Actavis Pharma, Inc. (2015):
  13. "Product Information. Caplyta (lumateperone)." Intra-Cellular Therapies, Inc. (2022):

• Kidney Diseases

  Moderate

  Clozapine is extensively metabolized by the liver and subsequently excreted in the urine (50%) and feces (35%), primarily as metabolites. One of the metabolites appears to have only limited pharmacologic activity, while the others are inactive. However, the effects of possible metabolite accumulation have not been studied. The manufacturer recommends that therapy with clozapine be administered cautiously in patients with impaired renal function.

  2 sources

  1. Jann MW, Grimsley SR, Gray EC, Chang WH "Pharmacokinetics and pharmacodynamics of clozapine." Clin Pharmacokinet 24 (1993): 161-76
  2. "Product Information. Clozaril (clozapine)." Novartis Pharmaceuticals (2001):

• Liver Diseases

  Moderate

  Most neuroleptic agents are extensively metabolized by the liver. The plasma concentrations of these agents may be increased and the half-lives prolonged in patients with impaired hepatic function. Therapy with neuroleptic agents should be administered cautiously in patients with significant liver disease. Lower initial dosages and slower titration may be appropriate.

  11 sources

  1. Hobbs DC, Welch WM, Short MJ, Moody WA, Van der Velde CD "Pharmacokinetics of thiothixene in man." Clin Pharmacol Ther 16 (1974): 473-8
  2. Hobbs DC "Metabolism of thiothixene." J Pharm Sci 57 (1968): 105-11
  3. Jann MW, Grimsley SR, Gray EC, Chang WH "Pharmacokinetics and pharmacodynamics of clozapine." Clin Pharmacokinet 24 (1993): 161-76
  4. "Product Information. Navane (thiothixene)." Roerig Division (2001):
  5. Heel RC, Brogden RN, Speight TM, Avery GS "Loxapine: a review of its pharmacological properties and therapeutic efficacy as an antipsychotic agent." Drugs 15 (1978): 198-217
  6. "Product Information. Clozaril (clozapine)." Novartis Pharmaceuticals (2001):
  7. "Product Information. Zyprexa (olanzapine)." Lilly, Eli and Company (2001):
  8. "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals (2001):

  Show all 11 sourcesShow fewer sources

  9. "Product Information. Moban (molindone)." Gate Pharmaceuticals (2001):
  10. "Product Information. Geodon (ziprasidone)." Pfizer U.S. Pharmaceuticals (2001):
  11. "Product Information. Loxitane C (loxapine)." Apothecon Inc (2022):

• Parkinsonian Disorders

  Moderate

  The use of neuroleptic agents is associated with pseudo-parkinsonian symptoms such as akinesia, bradykinesia, tremors, pill-rolling motion, cogwheel rigidity, and postural abnormalities including stooped posture and shuffling gait. The onset is usually 1 to 2 weeks following initiation of therapy or an increase in dosage. Older neuroleptic agents such as haloperidol are more likely to induce these effects, and their use may be contraindicated in patients with Parkinson's disease or parkinsonian symptoms.

  14 sources

  1. Moleman P, Janzen G, von Bargen BA, et al. "Relationship between age and incidence of parkinsonism in psychiatric patients treated with haloperidol." Am J Psychiatry 143 (1986): 232-4
  2. "Product Information. Haldol (haloperidol)." McNeil Pharmaceutical (2002):
  3. Heel RC, Brogden RN, Speight TM, Avery GS "Loxapine: a review of its pharmacological properties and therapeutic efficacy as an antipsychotic agent." Drugs 15 (1978): 198-217
  4. Bransgrove LL, Kelly MW "Movement disorders in patients treated with long-acting injectable antipsychotic drugs." Am J Hosp Pharm 51 (1994): 895-9
  5. Owens DGC "Extrapyramidal side effects and tolerability of risperidone - a review." J Clin Psychiatry 55 Suppl (1994): 29-35
  6. Pinder RM, Brogden RN, Swayer R, Speight TM, Spencer R, Avery GS "Pimozide: a review of its pharmacological properties and therapeutic uses in psychiatry." Drugs 12 (1976): 1-40
  7. Sheppard C, Merlis S "Drug-induced extrapyramidal symptoms: their incidence and treatment." Am J Psychiatry 123 (1967): 886-9
  8. Boston Collaborative Drug Surveillance Program "Drug-induced extrapyramidal symptoms." JAMA 224 (1973): 889-91

  Show all 14 sourcesShow fewer sources

  9. Mahmood T, Clothier EB, Bridgman R "Risperidone-induced extrapyramidal reactions." Lancet 346 (1995): 1226
  10. Gwinn KA, Caviness JN "Risperidone-induced tardive dyskinesia and parkinsonism." Mov Disord 12 (1997): 119-21
  11. "Product Information. Moban (molindone)." Gate Pharmaceuticals (2001):
  12. "Product Information. Orap (pimozide)." Gate Pharmaceuticals
  13. Talbert RL, Yee GC, DiPiro JT, Matzke GR, Posey LM, Wells BG "Pharmacotherapy: A Pathophysiologic Approach" Stamford, CT: Appleton & Lange (1999):
  14. "Product Information. Loxitane C (loxapine)." Apothecon Inc (2022):

• Pneumonia, Aspiration

  Moderate

  Esophageal dysmotility and aspiration have been associated with the use of antipsychotic drugs. These drugs should be administered cautiously in patients at risk for aspiration pneumonia.

  13 sources

  1. "Product Information. Clozaril (clozapine)." Novartis Pharmaceuticals (2001):
  2. "Product Information. Risperdal (risperidone)." Janssen Pharmaceuticals (2001):
  3. "Product Information. Zyprexa (olanzapine)." Lilly, Eli and Company (2001):
  4. "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals (2001):
  5. "Product Information. Geodon (ziprasidone)." Pfizer U.S. Pharmaceuticals (2001):
  6. "Product Information. Abilify (aripiprazole)." Bristol-Myers Squibb (2002):
  7. "Product Information. Invega (paliperidone)." Janssen Pharmaceuticals (2007):
  8. "Product Information. Fanapt (iloperidone)." Vanda Pharmaceuticals Inc (2009):

  Show all 13 sourcesShow fewer sources

  9. "Product Information. Saphris (asenapine)." Schering-Plough Corporation (2009):
  10. "Product Information. Latuda (lurasidone)." Sunovion Pharmaceuticals Inc (2010):
  11. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
  12. "Product Information. Vraylar (cariprazine)." Actavis Pharma, Inc. (2015):
  13. "Product Information. Caplyta (lumateperone)." Intra-Cellular Therapies, Inc. (2022):

• Seizures

  Moderate

  Antipsychotic and neuroleptic drugs can lower the seizure threshold and trigger seizures in a dose-dependent manner. This risk is greatest in patients with a history of seizures or with conditions that lower the seizure threshold. Therapy with these drugs should be administered cautiously in patients with a history of seizures or other predisposing factors, such as head trauma, CNS abnormalities, and alcoholism.

  13 sources

  1. "Product Information. Clozaril (clozapine)." Novartis Pharmaceuticals (2001):
  2. "Product Information. Risperdal (risperidone)." Janssen Pharmaceuticals (2001):
  3. "Product Information. Zyprexa (olanzapine)." Lilly, Eli and Company (2001):
  4. "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals (2001):
  5. "Product Information. Geodon (ziprasidone)." Pfizer U.S. Pharmaceuticals (2001):
  6. "Product Information. Abilify (aripiprazole)." Bristol-Myers Squibb (2002):
  7. "Product Information. Invega (paliperidone)." Janssen Pharmaceuticals (2007):
  8. "Product Information. Fanapt (iloperidone)." Vanda Pharmaceuticals Inc (2009):

  Show all 13 sourcesShow fewer sources

  9. "Product Information. Saphris (asenapine)." Schering-Plough Corporation (2009):
  10. "Product Information. Latuda (lurasidone)." Sunovion Pharmaceuticals Inc (2010):
  11. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
  12. "Product Information. Vraylar (cariprazine)." Actavis Pharma, Inc. (2015):
  13. "Product Information. Caplyta (lumateperone)." Intra-Cellular Therapies, Inc. (2022):

• Tardive Dyskinesia

  Moderate

  Tardive dyskinesia (TD) has occurred in patients treated with antipsychotic drugs; the syndrome consists of potentially irreversible, involuntary, dyskinetic movements. The risk appears highest in older patients (particularly older women) but it is not possible to predict which patients are likely to develop TD; whether antipsychotic drugs differ in their potential to cause TD is unknown. The risk of TD and the likelihood that it will become irreversible increase with the duration of therapy and the total cumulative dose. The syndrome can develop after relatively brief treatment periods, even at low dosages; it may also occur after discontinuation of therapy. TD may remit (partially or completely) upon discontinuation of antipsychotic therapy, although antipsychotic therapy itself may suppress (or partially suppress) signs/symptoms of TD, possibly masking the underlying process; the effect of symptomatic suppression on the long-term course of TD is unknown. In patients with preexisting drug-induced TD, initiating or increasing the dosage of antipsychotic therapy may temporarily mask the symptoms of TD but could eventually worsen the condition. In patients requiring chronic therapy, the lowest dose and shortest duration of therapy producing a satisfactory clinical response are recommended; the need for continued therapy should be reassessed periodically. If signs/symptoms of TD occur during antipsychotic therapy, discontinuation of the offending agent should be considered; however, some patients may require treatment despite the presence of TD.

  18 sources

  1. "Product Information. Abilify (ARIPiprazole)." Otsuka American Pharmaceuticals Inc (2020):
  2. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2021):
  3. "Product Information. Vraylar (cariprazine)." Allergan Inc (2019):
  4. "Product Information. Latuda (lurasidone)." Sunovion Pharmaceuticals Inc (2019):
  5. "Product Information. Seroquel (QUEtiapine)." Astra-Zeneca Pharmaceuticals (2022):
  6. "Product Information. Caplyta (lumateperone)." Intra-Cellular Therapies, Inc. (2022):
  7. "Product Information. Haldol (haloperidol)." Janssen Pharmaceuticals (2020):
  8. "Product Information. Thiothixene (thiothixene)." Amneal Pharmaceuticals LLC (2022):

  Show all 18 sourcesShow fewer sources

  9. "Product Information. Clozaril (cloZAPine)." HLS Therapeutics Inc (2021):
  10. "Product Information. RisperDAL (risperiDONE)." Janssen Pharmaceuticals (2021):
  11. "Product Information. ZyPREXA (OLANZapine)." Lilly, Eli and Company (2020):
  12. "Product Information. Moban (molindone)." Endo Laboratories LLC (2017):
  13. "Product Information. Pimozide (pimozide)." Par Pharmaceutical Inc (2017):
  14. "Product Information. Geodon (ziprasidone)." Pfizer Inc. (2022):
  15. "Product Information. Loxapine Succinate (loxapine)." Actavis U.S. (Amide Pharmaceutical Inc) (2016):
  16. "Product Information. Invega (paliperidone)." Janssen Pharmaceuticals (2022):
  17. "Product Information. Fanapt (iloperidone)." Vanda Pharmaceuticals Inc (2017):
  18. "Product Information. Saphris (asenapine)." Schering-Plough Corporation (2017):

• Thromboembolism

  Moderate

  Thromboembolic events such as deep-vein thrombosis and pulmonary embolism have been noted during clozapine therapy. Therapy with clozapine should be administered cautiously in patients with an active or past history of thromboembolic events.

  1 source

  1. "Product Information. Clozaril (clozapine)." Novartis Pharmaceuticals (2001):

• Weight Gain

  Moderate

  Weight gain has been observed with atypical antipsychotic use. While all agents in the class have been shown to produce some changes, each drug has its own specific risk profile. When treating pediatric patients with atypical antipsychotic agents, weight gain should be monitored and assessed against that expected for normal growth. Monitor weight at baseline and frequently thereafter.

  12 sources

  1. "Product Information. Clozaril (clozapine)." Novartis Pharmaceuticals (2001):
  2. "Product Information. Risperdal (risperidone)." Janssen Pharmaceuticals (2001):
  3. "Product Information. Zyprexa (olanzapine)." Lilly, Eli and Company (2001):
  4. "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals (2001):
  5. "Product Information. Geodon (ziprasidone)." Pfizer U.S. Pharmaceuticals (2001):
  6. "Product Information. Abilify (aripiprazole)." Bristol-Myers Squibb (2002):
  7. "Product Information. Invega (paliperidone)." Janssen Pharmaceuticals (2007):
  8. "Product Information. Fanapt (iloperidone)." Vanda Pharmaceuticals Inc (2009):

  Show all 12 sourcesShow fewer sources

  9. "Product Information. Saphris (asenapine)." Schering-Plough Corporation (2009):
  10. "Product Information. Latuda (lurasidone)." Sunovion Pharmaceuticals Inc (2010):
  11. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
  12. "Product Information. Vraylar (cariprazine)." Actavis Pharma, Inc. (2015):

Therapeutic duplication

Drug classes that overlap with Clozapine, so taking both doubles up the same effect. This source publishes no per-row citations for duplication.

• antipsychotics

  The recommended maximum number of medicines in the 'antipsychotics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'antipsychotics' category.

  Example product in the source data (US market): Fluoxetine/olanzapine

• antipsychotics

  The recommended maximum number of medicines in the 'antipsychotics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'antipsychotics' category.

  Example product in the source data (US market): Olanzapine/samidorphan

• antipsychotics

  The recommended maximum number of medicines in the 'antipsychotics' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'antipsychotics' category.

  Example product in the source data (US market): Amitriptyline/perphenazine