• Prolixin®
• Fluphenazine Omega®

• First-generation anti-psychotics (Typical)
• Phenothiazines

• Fluphenazine hydrochloride => orally or IM
• Fluphenazine decanoate => Slow Release => IV Injection form

1. Shizophrenia: Fluphenazine decanoate injections is a long-acting parenteral preparation

2. Maintenance treatment of non-agitated, chronic schizophrenia.

3. Not indicated for:

• Severely agitated psychotic patients, psychoneurotic patients or geriatric patients with confusion and/or agitation
• Children under 12 years of age.

Pharmacodynmics:

• Mechanism Of Action: Blocking dopamine and other catecholamine receptor sites.

Pharmacokinetics:

Absorption:

• Onset of action => 24 to 72 hours. Initial effects= > within 48 to 96 hours
• Onset of action: 24 and 72 hours after injection

Distribution:

Not fully elucidated; reportedly crosses blood-brain barrier.  Phenothiazines cross the placenta and are distributed into milk.

Metabolism:

• Highly protein-bound (greater than 90%) in plasma. Peak plasma concentration : 24-hours after intramuscular injection

Excretion:

• Serum half-life=> 7-10 days. Feces and Urine.

1. Adults Patients:

• Initial dose: 5 mg to 12.5 mg of fluphenazine decanoate (12.5 mg is usually well tolerated)/ 10 mg daily of fluphenazine hydrochlorid.
• Use fluphenazine hydrochloride dosages more than10 mg daily with caution! Safety of prolonged administration of dosages up to 40 mg daily not
• In particularly sensitive patients, a second dose of 12.5 mg or 25 mg can be given 4 to 10 days after the initial injection.
• Controlled with 25 mg or less, every two to three weeks.
• Max dose: 100mg only in some patients!
• Response to a single injection lasts usually two to three weeks; it may last for four weeks or more.
• Fluphenazine Omega 100 mg/mL may be administered in preference to Fluphenazine Omega 25 mg/mL in patients who complain of discomfort with a large injection volume or when a smaller injection volume is wanted.

2. Elderlies:

• The suggested initial test dose is 2.5 mg, gradually adjusted according to the response of the patient. Maintenance doses in the lower range (1/4 to 1/3 of those in younger adults) may be sufficient for most elderly patients.

• Fluphenazine Omega (fluphenazine decanoate injection) is usually given as an intramuscular injection gluteus Maximus and sometimes subcutaneously. Fluphenazine Omega is not for intravenous.

• CNS Depressants
• Alcohol
• Analgesics
• Tricyclic Antidepressants
• Lithium
• ACE inhibitors
• Thiazide Diuretics
• Guanethidine, clonidine and other adrenegic-blocking antihypertensive agents may be blocked. Clonidine may decrease the antipsychotic activity of phenothiazines.
• Beta Blockers: Plasma levels of both drugs may be increased.
• Metrizamide: Phenothiazines may predispose patients to metrizamide-induces seizures => Discontinue for 48 hours prior to (at least 24 hours ) myelography.
• Epinephrine and other sympathomimetics: Phenothiazines may antagonize the action of adrenaline and other sympathomimetics and may cause severe hypotension.
• Levodopa: Phenothiazines may impair the anti-Parkinson effect of L-Dopa
• Anticholinergics / Antimuscarinics: Cholinergic r muscarinergic blockade may be exaggerated when Fluphenazine is administered with anticholinergic agents, especially in older patients/ Atropine
• Anticonvulsants: Anticonvulsant action may be impaired by Fluphenazine.
• Anticoagulants: Phenothiazines may alter the effects of anticoagulants.

• Cimetidine: Cimetidine may reduce plasma concentrations (Enzyme inducer effect) of phenothiazines.
• Antacids / Antidiarrheal Agents: Concurrent administration may interfere with absorption. Administration of antacids should be spaced at least 1 hour before or 2-3 hours after fluphenazine dose.
• Amphetamine / Anorectic Agents: Concurrent administration may produce antagonistic pharmacologic effects.

More Frequent:

• Orthostatic Hypotension
• Fluctuations in blood pressure
• Extra Pyramid Side effects => Especially in Fluphenazine Omega (fluphenazine decanoate injection) = > Acute Dystonia, Akatasia, Parkinsonism, Rigidity, Tremor, tardive Dyskinasia
• Drowsiness or lethargy
• Neuroleptic malignant syndrome (NMS)

Less Frequent:

• Loss of appetite, salivation, polyuria, perspiration, dry mouth, headache, and constipation.
• Blurred vision
• Glaucoma,
• Bladder paralysis
• Fecal impaction
• Paralytic ileus
• Tachycardia
• Nasal congestion
• Weight change,
• Peripheral edema
• Hyponatremia
• Syndrome of inappropriate antidiuretic hormone secretion
• Abnormal lactation
• Gynecomastia
• Menstrual irregularities
• False results on pregnancy tests
• Impotency in men and libido changes in women have all been known to occur in some patients on phenothiazine therapy
• Allergic Reactions
• Leukopenia,
• Agranulocytosis,
• Thrombocytopenic or non-thrombocytopenic purpura
• Eosinophilia and pancytopenia
• Cholestatic jaundice

• Known hypersensitivity to Fluphenazine and other Phenothiazines.
• Marked cerebral athero-sclerosis
• Suspected or established subcortical brain damage, +/- hypothalamic damage, since a hyperthermic reaction with temperatures above 40C may occur, sometimes not until 14-16 hours after drug administration.
• Patients receiving large doses of CNS depressants => Alcohol, barbiturates, narcotics, hypnotics, etc => possibility of potentiation.
• Comatose or severity depressed states
• Blood dyscrasias
• Liver damage
• Renal insufficiency
• Pheochromocytoma
• Severe cardiovascular disorders

• Pregnancy: Category C
• Lactation: Not recommended in nursing mother

1. Fluphenazine exerts activity at various levels of the central nervous system as well as on peripheral organ systems:

• Less potentiating effect on central nervous system depressants and anesthetics than do some of the phenothiazines and appears to be less sedating => Be cautious for side effects!

2. Fluphenazine (Phenothiazines) cross the blood-brain barrier, placenta easily => cannot be removed by dialysis

3. Severe adverse reactions requiring immediate medical attention may occur and are difficult to predict => Monitor the patient closely!

4. Caution for sedative effect of Fluphenazine! Avoid driving or using dangerous machineries need full alertness.

5. The safety and efficacy of fluphenazine decanoate in children have not been established.

6. Neuroleptic Malignant Syndrome: potentially fatal syndrome in association with antipsychotic drugs => Symptoms: Muscular rigidity, fever, hyperthermia, altered consciousness and autonomic:

• Management: Immediate discontinuation of anti-psychotic drugs, intensive monitoring + treatment of symptoms, and treatment of any associated medical problems

7. Tardive dyskinesia: repetitive involuntary movements of the tongue, face, mouth or jaw => protrusion of the tongue, puffing the cheeks, puckering of the mouth, chewing movements. The trunk and limbs are less frequently involved. Risk is greater in elderly patients, especially females:

• Relatively irreversible
• Caused by cumulative dose of the drug increases
• In case of Tardive dyskinesia: Discontinue the medication
• There is no known effective treatment for tardive dyskinesia. Start Clozapin if indicated! (Has moderated effect in relieving symptoms)

8. Cerebrovascular Events: Increase the risk of cerebrovascular events especially in elderly patients. Caution is advised!

9. Possibility of cross-sensitivity => Fluphenazine decanoate injection should be used with caution in patients with cholestatic jaundice, and dermatoses, or other allergic reactions to phenothiazine derivatives.

10. Hypotensive phenomena may develop in phenothiazine-treated patients who are undergoing surgery => Careful observation is necessary

11. Caution for Anticholinergics effects of Fluphenazine => Paralytic ileus, even resulting in death, may occur especially in the elderly.

12. Fluphenazine decanoate should be used cautiously in patients exposed to extreme heat or phosphorus insecticides.

13. Neuroleptic drugs elevate prolactin levels; the elevation persists during chronic administration.

14. Test for phenylketonuria (PKU): False Positive test may occur.

15. Tests for pregnancy: False Positive test may occur.

16. Tests for urobilinogen, amylase, uroporphyrins, porphobilinogens, 5-hydroxyindolacetic acid: Urinary metabolites of phenothiazines may cause urine to darken and result in false-positive test results

17. Abrupt Withdrawl: Generally phenothiazines do not produce psychic dependence; however:

• Symptoms: gastritis, nausea and vomiting, dizziness, and tremulousness have been reported following abrupt discontinuation of high-dose therapy => concomitant antiparkinson agents therapy can diminish the withdrawal symptoms if administrated several weeks after phenothiazine is withdrawn.

18. Use in the Elderly:

• Used with care in elderly patients (>60 years old)
• Doses 1/4 to 1/3 of those in younger adults

19. Caution in patients with: pheochromocytoma, cerebral vascular or renal insufficiency, or a severe cardiac reserve deficiency => prone to hypotensive reactions with phenothiazine compounds.

20. Over-dosage:

• Symptoms: CNS depression progressing from drowsiness to coma with areflexia. Restlessness, confusion and excitement. Hypotension, tachycardia, hypothermia, pupillary constriction, restlessness, tremor, muscle twitching, spasm or rigidity, convulsions, muscular hypotonia, difficulty in swallowing or breathing, cyanosis, and respiratory and/or vasomotor collapse, possibly with sudden
• Treatment: Emesis should not be induce, Generally is supportive therapy
• In case of acute dystonic reactions: Intramuscular benztropine (or another antiparkinsonian agent- Dopamin agonist or Anticholinergics) should be given immediately (adults: 1 to 2 mg i.m, children: 0.2 mg i.m. initially with increments if necessary).

• LARGACTIL^®

• 1st generation Antipsychotics, Phenothiazines
• Tranquillizer

• Tablet: 10 mg, 25 mg, 100 mg
• Syrup (100ml): 25mg/5ml:
• Ampoules (2ml): 25mg/ml

1. Acute functional psychosis (e.g. schizophrenia, mania or psychotic depression).
2. Long-term treatment of schizophrenia.
3. Short-term treatment of:
   1. Agitation and behavioral disturbance in patients with delirium or dementia.
   2. Agitation and severe depression.
4. Severe behavioral disturbances, as can be found in some children with mental retardation or autism (including self-injurious, aggressive behavior or over activity.)
5. In management of terminal illness:
   1. To enhance the effect of analgesics.
   2. To control nausea and vomiting.
6. Control of intractable hiccough.

• Antagonize dopamine D2 receptors in brain;
• Depresses release of hypothalamic and hypophyseal hormones;
• Depress reticular activating system;
• Inhibits prolactin-release-inhibitory factor and stimulating the release of prolactin.

• Absorption:
  • Absorption route: gastrointestinal tract
  • Bioavailability: extensive first pass metabolism in the gut and the liver
  • Onset of action: 30-60 min
  • Duration of action: 4-6 hours, extended release: 10-12 hours
  • Peak plasma level:
    • following oral administration: 1-4 hours
    • Following intramuscular injection: 15 – 30 minutes.
• Distribution:
  • Widely distributed to the body tissue.
  • It crosses the blood-brain barrier and achieves higher concentrations in the brain than in the plasma.
  • Protein-bound: 90 – 99%
• Metabolism:
  • Metabolize pathway: by hepatic P450 enzyme CYP2D6
  • extensive first pass metabolism after oral administration
  • Chlorpromazine is almost completely metabolized.
• Elimination:
  • Half-life: 30 hours
  • Excretion: Significantly in the urine, in small amounts in faeces and in lesser amounts in sweat and hair.

• Adults:
  • Oral:
    • initial dose for ambulant patients: 25 mg three times daily
    • Max dose: 600mg-800mg per day.
    • maintenance doses: 25 to 100 mg three times daily
    • Crushing the tablets is not recommended, therefore Syrup should be replaced.
  • Parenteral:
    • deep intramuscular injection or intravenous infusion (after dilution with normal saline)
    • Blood pressure and vital signs should be taken before and monitored closely after injections.
    • Usual single dose: 25 to 50 mg by deep intramuscular injection (if necessary; repeat three to four times in 24 hours.)
    • Intramuscular injection part: upper outer quadrant of the buttock or upper portion of the deltoid muscle.
• Children:
  • Over 5 years of age: one third to one half of adult dosage is given
  • Younger than 5 years old: oral dose is calculated on the basis of 0.5 mg/kg bodyweight.
    • 5 mg at 1 year
    • 5 mg at 3 years
    • 10 mg at 6 years.
  • Doses may be repeated three or four times a day.
  • Children need to be monitored for hypothermia and hypotension.
• Hepatic or Renal Impairment:
  • The dosage in these patients may need to be reduced
• Elderly or Debilitated:
  • The dosage in these patients may need to be reduced

1. Interactions resulting in decreased chlorpromazine levels:
   • Food,
   • Alcohol
   • Benztropine
   • Antacids
   • Lithium
   • Chronic administration of barbiturates
2. Interactions resulting in increased chlorpromazine levels:
   • Tricyclic antidepressants
   • CYP1A2 inhibitors: ciprofloxacin, fluvoxamine, oral contraceptives, thiabendazole, vemurafenib
3. Interactions in which other drugs are affected by chlorpromazine:
   • Central nervous system depressants, benzodiazepines, anesthetic drugs, opioids, barbiturates, lithium, valproic acid, phenytoin, propranolol, adrenaline, guanethidine, clonidine, antidiabetic agents, levodopa, amphetamines, oral anticoagulants, Thiazide diuretics, quinidine, MAOIs, suxamethonium, organophosphorus insecticides, atropine, desferrioxamine.
4. Interaction with drugs that:
   • increase risk of QT prolongation:
     • Class Ia antiarrhythmic agents: quinidine and disopyramide.
     • Class III antiarrhythmic agents: amiodarone and sotalol.
     • Other medications: bepridil, cisapride, sultopride, thioridazine, methadone, intravenous erythromycin, intravenous vincamine, halofantrine, pentamidine, sparfloxacin.
   • Induce bradycardia:
     • Calcium channel blockers (diltiazem, verapamil), beta-blockers, clonidine, guanfacine, and digitalis.
   • Cause hypokalemia:
     • Diuretics, stimulant laxatives, intravenous amphotericin B, glucocorticoids, tetracosactides.

More Common Adverse Effects

• Cardiovascular: Postural hypotension, ECG Changes.
• Dermatological: Contact dermatitis, photosensitivity, urticarial, maculopapular, petechial or edematous reactions.
• Endocrine: Elevated prolactin levels, impaired thermoregulation, hyperglycemia, other hypothalamic effects.
• Gastrointestinal: Dry mouth, constipation.
• Immunological: Raised ANA titer, positive SLE cells.
• Genitourinary: Urinary retention.
• Hematological: Leucopenia, agranulocytosis, eosinophilia, hemolytic anemia, aplastic anemia, thrombocytopenic purpura and pancytopenia have been reported.
• Nervous System:
  • Autonomic: dry mouth, mental confusion, postural hypotension, nasal congestion, nausea, obstipation, constipation, adynamic ileus, urinary retention, priapism, miosis and mydriasis, atonic colon, ejaculatory disorders/impotence.
  • Central: extrapyramidal reactions (Parkinsonism, akathisia) tardive dyskinesia, non-extrapyramidal effects including lowering of seizure threshold and paradoxical effects, e.g. agitation, excitement and aggravation of schizophrenic symptoms; drowsiness, dystonia, motor restlessness.
• Ocular: Blurred vision, photophobia, miosis, mydriasis, corneal deposits.
• Respiratory: Stuffy nose, respiratory depression.
• Local Reactions (injection): Pain at injection site, injection abscess.
• General: Weight gain.

 Less Common Adverse Effects

• Cardiovascular: Arrhythmias, hypertensive crisis (following abrupt withdrawal), A-V block, ventricular tachycardia, QT interval prolongation and fibrillation, sudden death
• Dermatological: Skin pigmentation and purpura, exfoliative dermatitis and toxic epidermal necrolysis.
• Endocrine: Hyperthermia, hypothermia, lactation and moderate breast engorgement in females on large doses, false-positive pregnancy tests, amenorrhea, gynecomastia, hypoglycemia, glycosuria.
• Gastrointestinal: Paralytic ileus.
• General: systemic lupus erythematosus, Allergic reactions
• Genitourinary: Inappropriate ADH secretion, water retention, edema, incontinence.
• Hematological: Coagulation defects.
• Hepatic: Cholestatic jaundice and liver injury.
• Musculoskeletal: Neuroleptic malignant syndrome, myasthenia gravis.
• Nervous System: Fits, cerebral edema, nightmares, abnormality of cerebrospinal fluid proteins.
• Ocular: Precipitation/aggravation of narrow angle glaucoma, optic atrophy, pigmentary retinopathy, lens opacities.
• Psychiatric: Dysphoria, catatonic excitement.

 Serious or Life Threatening Reactions

• Hypothermia or hyperthermia
• Cardiac arrhythmia
• Agranulocytosis
• Progressive hepatic fibrosis
• Malignant hyperpyrexia
• Sudden Death
• Tardive Dyskinesia
• Neuroleptic Malignant Syndrome

 Other adverse effects

• Metabolism and nutrition disorders: Hyper-triglyceridaemia, hyponatremia, Glucose intolerance and hyperglycemia
• Gastrointestinal disorders: Colitis ischemic, gastrointestinal necrosis, necrotizing colitis, intestinal perforation.
• Skin and subcutaneous tissue disorders: Angioedema, urticaria.

1. Circulatory collapse
2. CNS depression (e.g. coma or drug intoxication.)
3. Previous history of a hypersensitivity reaction
4. Bone marrow depression
5. Pheochromocytoma
6. Hepatic failure or active hepatic disease.
7. LARGACTIL Syrup contains sodium metabisulfite, sodium sulfite and sodium benzoate and LARGACTIL Injection contains sodium metabisulfite and sodium sulfite and may cause allergic-type reactions including anaphylactic symptoms and asthmatic episodes in susceptible people.

• Pregnancy: Category C
• Lactation: not recommended for nursing mothers

1. Should not be used in: Epilepsy, Parkinson’s disease, hypoparathyroidism, myasthenia gravis and prostatic hypertrophy.
2. Antiemetic Effects: The antiemetic effects of chlorpromazine may mask signs of over-dose of toxic drugs or diagnosis of intestinal obstruction and brain tumor.
3. Temperature Regulation: Phenothiazine depress the mechanism for regulation of temperature >>> Severe hypothermia may occur during swimming in cold water or in patients receiving antipyretic therapy, and heat stroke may occur in hot weather.
4. Prolonged Usage: Long term usage could cause the development of tardive dyskinesia.
5. Alertness: Chlorpromazine impair mental and physical abilities (especially during the first few days of therapy.) >>> caution patients about activities requiring alertness.
6. Agranulocytosis:
   1. Agranulocytosis has been reported at an incidence of between 1:1,300 and 1:500,000. Most reported cases have occurred between the fourth and tenth week of treatment.
   2. Warn patients to report the sudden appearance of sore throat, fever or other signs of infection. If white blood cell and differential counts indicate cellular depression, stop treatment and start antibiotic and other suitable therapy, subject to the expert guidance of a hematologist.
7. Liver Dysfunction:
   1. Because of extensive hepatic metabolism chlorpromazine >>> caution should be taken in treating patients with hepatic impairment >>> Dose reduction is necessary.
   2. If bilirubinemia, bilirubinuria or icterus occur >>> discontinued treatment
8. Retinopathy: Periodic eye examinations should be performed during prolonged therapy.
9. Respiratory Disease: Chlorpromazine might suppress cough reflex >>> aspiration of vomitus is possible >>> Chlorpromazine should be used with caution in patients with chronic respiratory disorders.
10. Reye’s syndrome:
    1. Chlorpromazine should be avoided in children and adolescents with signs and symptoms of Reye’s syndrome.
    2. The extrapyramidal symptoms which can occur secondary to chlorpromazine may be confused with the central nervous system signs of Reye’s syndrome or other encephalopathy.
11. Renal disease: Chlorpromazine should be given cautiously to patients with renal disease.
12. Glaucoma and Neuroleptic Malignant Syndrome: Should be used with caution in patients with glaucoma and features of neuroleptic malignant syndrome include autonomic dysfunction.
13. Photosensitivity: Patients should be warned about photosensitivity in sunny weather.
14. Hypotension: Extreme caution in cardiovascular disease, hemochromocytoma, conditions with a sudden drop in blood pressure, usage in conjunction with other drugs which cause postural hypotension.
15. QT Intervals: Phenothiazines potentiate QT interval prolongation >>> increases the risk of the torsade de pointes.
16. Cerebrovascular Events: There is an increased risk of cerebrovascular events in elderly patients with dementia.
17. Venous Thromboembolism: chlorpromazine should be used with caution in patients with risk factors for thromboembolism
18. Use in the Elderly: Elderly are more susceptible to the adverse effects >>> starting dose should be about half the usual adult dose and dosage increments should be gradual and reviewed regularly.
19. Elderly Patients with Dementia: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.
20. Hyperglycemia: Hyperglycemia or glucose intolerance might happen >>> Diabetic patients or patients with risk factors of diabetes should get glycemic monitoring during treatment.
21. Effects on Fertility: Chlorpromazine may cause hyperprolactinemia >>> associated with impaired fertility in women.
22. Effect on Laboratory Tests: Phenothiazines might produce false positive phenylketonuria (PKU) test results.
23. Over-dose:
    1. Symptoms: CNS depression, drowsiness, coma, areflexia, restlessness, confusion, excitement, hypotension, tachycardia, hypothermia, pupillary constriction, tremor, muscle twitching, spasm or rigidity, convulsions, muscular hypotonia, difficulty in swallowing and breathing, cyanosis and respiratory and/or vasomotor collapse, sudden apnea, Polyuria has also been noted which may result in dehydration
    2. Treatment: Symptomatic and supportive treatment should be administered.

• Compzine®
• Stemzine®
• Buccastem®
• Stemetil®
• Phenotil®

• First-generation anti-psychotics (Typical)
• Phenothiazines

• Tablets: 5 mg, 10 mg
• Suppository: 25 mg
• Injectable Solution: 5mg/mL

• Migraine
• Vertigo due to Meniere’s syndrome
• Labyrinthitis
• Others

Pharmacodynamics:

Mechanism of action:

• Anti-dopamine action
• Adrenoreceptor antagonism => cardiovascular side effects such as orthostatic hypotension and reflex tachycardia.
• Potentiation of noradrenaline by blocking its reuptake into nerve terminals.
• Weak anticholinergic action.
• Weak antihistamine action.
• Weak serotonin antagonism.
• Has an effect on temperature control and blocks conditioned avoidance responses.

Pharmacokinetics:

•  Absorption: GI tract (Orally –Po)
• Distribution: widely distributed to tissues including the brain, fat, kidney, heart and skin and is stored in reticuloendothelial tissues.
• Metabolism: Enterohepatic circulation
• Excretion: Very small amount (0.1%) of prochlorperazine and its metabolites (N-desmethyl Prochlorperazine => active metabolite) are excreted in the first 24 hours in the urine and the drug may continue to be excreted in the urine for up to 3 weeks after cessation of long term therapy. half-life is approximately 24 hours.

1. Nausea and Vomiting (Adults):

• Acute attack: 20 mg at once, followed, if necessary by 10 mg two hours later Maintenance dose: 5 or 10 mg two or three times daily.

• Attention: If oral administration is not practical, a deep intramuscular injection of 1 mL (12.5 mg) or a 25 mg suppository should be used, followed if required, by normal oral medication six hours later.
• Do not use a darkened solution for injection (more than pale yellow).
• Adjust the dose to the lowest clinically effective possible.

2. Nausea and Vomiting (Children):

• Preferebly do not use prochlorperazine for children. However if it is considered unavoidable => the dosage is 250 micrograms/kg
• Bodyweight two or three times a day.
• After a cumulative dosage of 500 micrograms/kg=> Watch out for dystonic reactions has been associated with Prochlorperazine => It should therefore be used cautiously in children.
• Not recommended for children weighing less than 10 kg and should not be given to children by the rectal or intramuscular route.
• When treating children, it is recommended that the 5 mg tablets be used.

3. Vertigo and Meniere’s Disease:

Adults:

• Oral: 5 to 10 mg three or four times daily. Dosage may be reduced gradually after several weeks to a maintenance dosage of 5 to 10 mg daily.

Children:

• Oral: Dose, same as for nausea and vomiting.

Geriatric:

• Dosages in the lower range are sufficient for most elderly patients. Dosage should be increased more gradually in elderly patients.

4. Impaired Liver Function:

 Prochlorperazine is extensively metabolised by the liver. Thus, dosage reduction may be necessary.

• Class Ia antiarrhythmics: Quinidine and Disopyramide
• Class III antiarrhythmics: Amiodarone and Sotalol
• Bepridil
• Cisapride
• Sultopride
• Thioridazine
• Methadone
• Intravenous erythromycin
• Intravenous vincamine
• Halofantrine
• Pentamidine
• Sparfloxacin
• Medicines which induce bradycardia: bradycardia-inducing calcium channel blockers (diltiazem, verapamil), beta-blockers, clonidine, guanfacine, digitalis
• Medicines which can cause hypokalaemia: such as diuretics, stimulant laxatives intravenous amphotericin B, glucocorticoids, tetracosactides
• Other antipsychotics.
• Alcohol (Ethanol)
• Desferrioxamine

More frequent:

• Gastrointestinal
• Constipation
• Dry mouth
• Nervous System
• Drowsiness
• Akathisia
• Parkinsonism (dyskinesia, tremor and rigidity)
• Blurred vision

Less frequent:

• Biochemical abnormalities: Elevated serum levels of bilirubin and hepatic enzymes may occur if the patient develops cholestatic jaundice.
• Hypotension
• Peripheral oedema
• Cardiac arrhythmias
• QT interval prolongation
• Sudden cardiac death
• Venous thromboembolism
• Pulmonary embolism
• Dermatitis or contact dermatitis
• Maculopapular eruptions
• Erythema multiforme
• Urticarial
• Photosensitivity
• Abnormal pigmentation
• Elevated prolactin levels
• hyperglycaemia
• Hypoglycemia
• Menstrual irregularities
• Galactorrhoea
• Gynaecomastia
• Paralytic ileus
• Agranulocytosis
• Atypical lymphocytes
• Thrombocytopenia
• Leucopenia
• Aplastic anaemia
• Acute dystonic reactions
• Seizures
• EEG changes
• Headache
• Insomnia
• Catatonia
• Hyperpyrexia
• Pigmentary rentinopathy
• Activation of psychotic symptoms
• Respiratory depression

• Circulatory collapse
• Central nervous system depression (coma or drug intoxication)
• Previous history of a hypersensitivity reaction
• Bone marrow depression
• Renal dysfunction
• Parkinson’s disease
• Hypothyroidism
• Pheochromocytoma
• Myasthenia gravis
• Prostate hypertrophy

• Pregnancy: Category C
• Lactation: Not recommended in nursing mothers

1. Should be avoided in patients with renal dysfunction, Parkinson’s disease, hypothyroidism, phaeochromocytoma, myasthenia gravis and prostate hypertrophy.

2. Patients with hypotension: The autonomic side effects of the piperazine derivatives are less troublesome than those of other phenothiazines, however care should be taken if prochlorperazine is used in the elderly or in patients undergoing surgery with spinal anaesthesia.

3. Epileptic patients: Piperazine derivatives are also less epileptogenic than other phenothiazines, but care should still be exercised in epileptic patients.

• Phenothiazines may lower the convulsive threshold; dosage adjustments of anticonvulsants may be necessary

4. Anticholinergic side- effects: Prochlorperazine can cause problems due to anticholinergic effects, especially in the elderly (urinary difficulties, constipation and precipitation of acute narrow angle glaucoma), but to a lesser extent than with other phenothiazines.

5. Hypocalcaemia: Patients with hypoparathyroidism => prone to acute dystonic reactions with prochlorperazine.

6. Sedative effect: Prochlorperazine may impair mental and physical activity especially during the first few days of therapy:

• Avoid driving while taking prochlorperazine.
• Avoid working with dangerous machineries need concentration and full alertness.

7. Antiemetic effects: The antiemetic effects of prochlorperazine may mask signs of over dosage of toxic drugs or obscure the diagnosis of conditions such as intestinal obstruction, brain tumour. Caution along with close follow ups is advised!

8. Reye’s Syndrome and hepatic-encephalopatic patients: The use of prochlorperazine and other potential hepatotoxins should be avoided in children and adolescents whose signs and symptoms suggest Reye’s Syndrome and hepatic-encephalopathy.

9. Hypothermia: Severe hypothermia may occur during swimming in cold water or in patients receiving antipyretic therapy concomitantly with Prochlorperazine.

10. Liver disease: Caution should be used in patients with existing liver disease due to the extensive hepatic metabolism of prochlorperazine.

11. Tardive dyskinesia: repetitive involuntary movements of the tongue, face, mouth or jaw => protrusion of the tongue, puffing the cheeks, puckering of the mouth, chewing movements. The trunk and limbs are less frequently involved. Risk is greater in elderly patients, especially females:

• Relatively irreversible
• Caused by cumulative dose of the drug increases
• In case of Tardive dyskinesia : Discontinue the medication
• There is no known effective treatment for tardive dyskinesia. Start Clozapin if indicated! (Has moderatet effect in relieving sympotoms)

12. Neuroleptic Malignant Syndrome: potentially fatal syndrome in association with antipsychotic drugs => Symptoms: Muscular rigidity, fever, hyperthermia, altered consciousness and autonomic:

• Management: immediate discontinuation of anti-psychotic drugs, intensive monitoring + treatment of symptoms, and treatment of any associated medical problems

 13. QT Interval: QT interval prolongation => torsade de pointes type, which is potentially fatal (sudden death). QT prolongation is exacerbated, in particular, in the presence of bradycardia, hypokalemia, and congenital or acquired (i.e., drug induced) QT prolongation. If the clinical situation permits, medical and laboratory evaluations should be performed to rule out possible risk factors before initiating treatment.

14. Cerebrovascular Events: Increase the risk of cerebrovascular events especially in elderly patients. Caution is advised!

15. Thromboembolism: Increased the risk of venous thromboembolism. Caution is advised!

16. Elderly Patients with Dementia: Elderly patients with dementia-related psychosis =>increased risk of death.

17. Hyperglycaemia: Patients with an established diagnosis of diabetes mellitus or with risk factors for the development of diabetes who are started on prochlorperazine, should get appropriate glycaemic monitoring during treatment.

18. Prochlorperazine is not recommended for use in children under 10 kg in weight or less than 2 years of age => acute extrapyramidal reactions may occur.

• Attention: Prochlorperazine should not be given to children by the rectal or intramuscular route.

19. Do not consume Alcohol while taking Prochlorperazine: May enhance the CNS depressant effects of alcohol and other depressant drugs + potentiate the anticholinergic effects of atropinic agents + tricyclic antidepressants.

20. In patients taking Desferrioxamine: Simultaneous administration may cause transient metabolic encephalopathy characterised by loss of consciousness for 48-72 hours.

21. Patients taking Thiazide diuretics: May accentuate the orthostatic hypotension that may occur with phenothiazines.

22. Caution in patients on anti-coagulants: Phenothiazines can decrease the effect of oral anticoagulants.

23. Concomitant administration of propranolol with phenothiazines results in increased plasma levels of both drugs.

24. Over-dosage:

• Symptoms: CNS depression progressing from drowsiness to coma with areflexia. Restlessness, confusion and excitement. Hypotension, tachycardia, hypothermia, pupillary constriction, restlessness, tremor, muscle twitching, spasm or rigidity, convulsions, muscular hypotonia, difficulty in swallowing or breathing, cyanosis, and respiratory and/or vasomotor collapse, possibly with sudden
• Treatment: Emesis should not be induce, Generally is supportive therapy
• In case of Acute dystonic reactions: Intramuscular benztropine (or another antiparkinsonian agent- [Dopamin agonist / Anticholinergics]) should be given immediately (adults: 1 to 2 mg i.m., children: 0.2 mg i.m. initially with increments if necessary).

• ProSom®

• Eurodin®

• Benzodiazepines
• Sedative-hypnotics

• Tablets: 1mg, 2mg

Insomnia: short-term treatment (no more than 7-10 days)

Pharmacodynamics:

• Mechanism of action: Decrease the activity of CNS by increase the inhibitory effect of neurotransmitter GABA on neurone

Pharmacokinetics:

• Absorption: gastrointestinal tract
• Distribution: 93% bound to protein in plasma
• Metabolism: hepatic (Metabolized by Cytochrome P450 3A)with 0.5-6 hours(mean: 2 hours) peak plasma time and 13.5 to 34.6(mean: 18 hours) hours half-life
• Excretion: urine (4% in feces)

Adults:

• Initial dose: start 1 mg/bedtime, if no responseàincrease to 2 mg
• Maximum dose: 2 mg/day
• Geriatric or Debilitated Patients: Smaller dose => 0.5 mg /bedtime

Pediatrics: It is not recommended under 18 years of age

Concomitant use with medications having Enzyme inhibitor effect (Cytochrome p450) Increase plasma concentration of Estazolam :

• Ketoconazole
• Itraconazole
• Erythromycin
• Nefazodone
• Fluvoxamine
• Cimetidine
• Diltiazem
• Isoniazid
• Macrolides

Concomitant use with medications having Enzyme inducer effect (Cytochrome p450) decrease plasma concentration of Estazolam :

• Carbamazepine
• Phenytoin
• Rifampin
• Barbiturates

More than 10% :

1. Somnolence
2. Headache
3. Hypokinesia
4. Dizziness
5. General weakness
6. ataxia

Less than 10% :

1. Anaphylaxis and angioedema
2. Respiratory depression(esp: in respiratory compromise patients)
3. Abnormal thoughts
4. Confusion
5. Seizure
6. Sleep disorder
7. Drug dependence

1. Known hypersensitivity to medication
2. Pregnancy(congenital malformations)
3. Simultaneous prescription of ketoconazole or Itraconazole

• Pregnancy: Category X
• Lactation: Not Recommended in nursing mother

1. plasma clearance is increased in smokers.

2. Taper slowly, if it is used for more than 6 weeks (prolong therapy)=>To avoid withdrawal symptoms

3. Use with caution in acute alcohol intoxication

4. In pregnancy => increase fetal morbidity and mortality

5. If insomnia worsen or new psychiatric symptoms appears, it should raise the suspicion of other underlying disease.

6. Daytime sleepiness and dizziness => Be cautious for sleep-related behaviors(driving)

7. Abnormal psychiatric problems are reported: combativeness, excitement, bizarre behavior, agitation, hallucinations, depersonalization, amnesia

8. Use with caution in depressed patients=> increase suicidal thoughts

9. Not use alcohol concomitantly

10. Avoid prescription with Ketoconazole, Itraconazole

11. Failure of treatment indicates possible underlying disease

12. Abuse: Caution in administering Oxazepam to individuals known to be addiction prone or those whose history suggests they may increase the dosage on their own initiative.

13. Dependence: The use of benzodiazepines may lead to dependence as defined by the presence of a withdrawal syndrome on discontinuation of the drug.

14. Tolerance: As defined by a need to increase the dose in order to achieve the same therapeutic effect seldom occurs in-patients receiving recommended doses under medical supervision >>> Caution for Tolerance to sedation may occur with benzodiazepines especially in those with drug seeking behaviour.

15.  Impaired Respiratory Function: Caution in the use of Estazolam is recommended in-patients with respiratory depression. In-patients with chronic obstructive pulmonary disease, benzodiazepines can cause increased arterial carbon dioxide tension and decreased arterial oxygen tension.

16. Avoid driving while taking Estazolam!

17. Avoid using dangerous machinery vehicles while taking Estazolam!

18. Caution in concomitant use with CNS-depressant medications! May cause synergistic effect => may increase sedation!

19. Over-dosage:

• Clinical manifestations has wide ranges, from drowsiness to coma
• Treatment: 1) Activated charcoal should be given to reduce absorption. 2) Do supportive treatments for any possible respiratory depression or hypotension
• Flumazenil => 0.2 mg IV in 13-30 minutes >>> If no response after 30 minutes, add 0.3 mg in 30 seconds one minute later. Maximum total dose: 3 mg/hr (contact your regional Poison Control Centre for more information)

• Tranxene®

• Benzodiazepines
• Anxiolytics
• Sedatives
• Anti-Consultants

Tablets: 3.75 mg, 7,5 mg, 15 mg 

1. Pathological anxiety : short-term symptomatic relief

• Acute Panic Attack
• Limited Social phobia

2. psychoneurotic patients: short-term relief of tension(those with functional somatic complains)

3. seizure

4. Alcohol withdrawal: (adjunctive therapy)

Pharmacodynamics:

• Mechanism of action & Pharmacodynamics: Rapidly decarboxylated to form nordiazepam (N-desmethyldiazepam)

Pharmacokinetics:

• Absorption: Gastrointestinal tract
• Distribution: penetrates the brain rapidly, plasma concentration of nordiazepam in 5 days to 2 weeks. Peak serum level of 1-2 hours
• Metabolism: hepatic
• Excretion: urine, half-life: 48 hours

1. Adults:

• Initial: 15 to 60 mg/day. It is suitable to start with 15mg/day, then increase the dose to reach the desired goal. Properly, prescribe every night once daily (also can be divided into two doses).
• Maximum dose: 60 mg/day

•  Debilitated and Elderly Patients: Initial: 3.75 mg/day (preferably at night), then increase slowly and carefully to stabilize the patient.
• Acute alcoholic withdrawal: First 24 hours: 30-90mg in divided doses (depend on response and tolerance) Second 24 hours: the dosage should be reduced to not more than 60 mg in divided doses. Till 4^th day: reduce slowly, not more than 15-30mg, and then taper off rapidly to discontinue.

2. Pediatrics: It is not recommended

•  When relief of symptoms are observed, reduce to lowest dosage in which no symptoms return
• If the dosage exceeds 20mg/day in elderly, cardiovascular system should be monitored

• Sodium oxybate
• Idelalisib
• Ivacaftor
• Acetaminophen / propoxyphene
• Albuterol
• Alfentanil
• Alprazolam
• Amitriptyline
• Aspirin / Caffeine / Propoxyphene
• Buprenorphine
• Clozapine
• Fluoxetine / Olanzapine
• Antacids

Most common => drowsiness

Less common (in descending order):

• Dizziness
• Gastrointestinal complaints
• Nervousness
• Blurred vision
• Dry mouth
• Headache
• Mental confusion
• Insomnia,
• Transient skin rashes
• Fatigue
• Ataxia
• Genito-urinary complaints
• Irritability
• Diplopia
• Depression
• Slurred speech
• Hypotension and dysfunction liver and kidney tests

1. Hypersensitivity to this drug
2. Myasthenia gravis

• Pregnancy: Not recommended => great risk of malformations
• Lactation: Not Recommended in nursing mother

1. Concurrent use of antacids with clorazepate may reduce 12% of bioavailability of this drug

2. It is not recommended for use in:

• Anxiolytic to address everyday life stress
• Depressive neuroses
• Treatment of psychotic or severely depressed patients
• Psychotic reactions
• Patients less than 18 years of age

3. Use with caution in the setting of other CNS depressant drugs (e.g. benzodiazepines may be potentiated by barbiturates, narcotics, phenothiazines, monoamine oxidase inhibitors), because of its CNS depressant effect

4. Clorazepate increases the effect of alcohol and chlorpromazine.

5. Increasing sedation: Use with caution in patients who is working in dangerous occupations that need mental alertness. Avoid driving and using dangerous machineries while taking medication.

6. Long-term use=> do complete blood counts and liver function tests periodically(also renal precautions in patients with kidney disease)

7. Malformations has been published in the infant of a mother who had taken this drug during the first trimester of pregnancy.

8. Do NOT prescribe for patients prone to drug abuse.

9. Use with caution in those who have potential risk for psychological dependence=>

• withdrawal symptoms after abrupt discontinuation: insomnia, nervousness, irritability, muscle aches, diarrhea, tremor, and memory impairment
• Do not do abrupt discontinuation

10. Be administered with caution to patients with acute narrow-angle glaucoma.

11. Elderly and disabled patients or organic brain syndromeàbecause of their susceptibility to CNS depression, administer with low dose and increase gradually if needed.

12. Clorazepate overdose treatment=> Supportive therapy is recommended:

• Flumazenil ( Benzodiazepines antidotes) may induce seizures in patients with a history of seizures disorder or who are on tricyclic antidepressants.
• Over-dosage:
• • Clinical manifestations has wide ranges, from drowsiness to coma
  • Treatment: 1) Activated charcoal should be given to reduce absorption. 2) Do supportive treatments for any possible respiratory depression or hypotension
  • Flumazenil >>> 0.2 mg IV in 13-30 minutes >>> If no response after 30 minutes, add 0.3 mg in 30 seconds one minute later. Maximum total dose: 3 mg/hr (contact your regional Poison Control Centre for more information)

13. This drug may cause=> aggression, antegrade amnesia

• Pristiq®

• Antidepressant
• Serotonin–norepinephrine reuptake inhibitors (SNRIs)

• Tablets: 50 and 100 mg extended-release 

• Adults: symptomatic relief of major depressive disorder.
• Pediatrics: Not recommended in less than 18 years old

Pharmacodynamics:

• Mechanism of action:

It is a major active metabolite of venlafaxine a serotonin and norepinephrine reuptake inhibitor (SNRI)

Pharmacokinetics:

Absorption:

• Bioavailability: 80%
• Peak plasma time: 7.5 hr
• Plasma concentration: 4-5days

Distribution:

• Protein bound: 30%
• Volume of distribution (Vd): 3.4L/kg

Metabolism:

• Metabolized in liver by CYP3A4

Elimination and excretion:

• Half-life: 11 hr
• Long-term efficacy of Pristiq is 26 weeks
• Excretion: urine (45%)

Acute Major Depression:

• Initial dose=> 50 mg/day, Maximum standard dose => 100mg/day
• Administration: Swallow with liquids

Renal impairment dose adjustment:

In severe renal impairment (24-hr CrCl<30mL/min) or end-stage renal disease (ESRD) the recommended dose is 50 mg/day.

Hepatic impairment dose adjustment:

No dosage adjustment is needed.

*Note:

• The patient should be reevaluate periodically to ascertain any need for maintenance treatment.
• It’s recommended to taper this drug or any other antidepressant (if you want to switch to Pristiq) gradually to reduce the possibility of discontinuation symptoms (dizziness, nausea, headache, irritability, diarrhea, anxiety, abnormal dreams, fatigue, and hyperhidrosis).
• There should be at least 14days between discontinuation of MAOI and starting Pristiq, moreover it should be 7days after stopping Pristiq and initiation of MAOI.

1. Selective serotonin reuptake inhibitor (SSRI)

2. Serotonin norepinephrine reuptake inhibitor (SNRI)

3. Lithium

4. Sibutramine

5. Fentanyl and its analogues

6. Dextromethorphan

7. Tramadol, Tapentadol

8. Meperidine, Methadone and Pentazocine

9. MAOIs and Linezolid, Methylene blue => May impair serotonin metabolism

• may set the stage for a life-threatening situation which is serotonin syndrome or Neuroleptic Malignant Syndrome (NMS)-Like Reactions (tremor, myoclonus, diaphoresis, nausea, vomiting, flushing, dizziness, hyperthermia, seizures, rigidity, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes).

10. NSAIDs: Non-steroidal anti-inflammatory drugs

11. ASA and other anticoagulants:

• Drugs that interfere with hemostasis and consequently cause bleeding (because serotonin mechanism is a key role in hemostasis and Pristiq impair this process)

1. More frequent:

• Gastrointestinal disorders (Nausea, Dry mouth, Constipation, Vomiting)
• General disorders (Fatigue, Chills, asthenia, Feeling jittery)
• Decreased appetite, Dizziness, dizziness, insomnia, Hyperhydrosis

2. Less Frequent: 

• Cardiac disorders (Blood pressure increased, palpitations, tachycardia)
• Nervous system disorders (Somnolence, Tremor, and Disturbance in attention)
• Psychiatric disorders (Insomnia, Anxiety, Nervousness, Abnormal dreams)
• Special Senses (Vision blurred, Mydriasis, Vertigo, Tinnitus, Dysgeusia)
• Urinary hesitation, Yawning, Hot flush.
• Sexual Function (in men: erectile dysfunction and ejaculation delayed, Anorgasmia, Libido decreased, and Orgasm abnormal- in women: Anorgasmia)

Serious and sometimes fatal when it is used concurrently with:

1. Monoamine oxidase inhibitors (MAOIs) or patients who have treated with MAOIs since 14 days => Its recommended to give a 7-day period after stopping desvenlafaxine (regarding its half-life) and then start an MAOI.
2. Linezolid 
3. A dye in some surgeries
4. Known hypersensitivity to the medication.

• Pregnancy: Category C
• Lactation:Not recommended in nursing mother

1. Pediatrics=>Increase the risk of suicidality:

• Administration under 18 year-old might be followed by behavioral and emotional changes, including self-harm or suicide.

2. Adults: Prescribe with caution in these conditions:

• Allergic Reactions, Bone Fracture Risk, syndrome of inappropriate antidiuretic hormone (SIADH), possibility of gastrointestinal obstruction, abnormal bleeding, seizure
• Increase in blood pressure, cholesterol, and triglycerides
• It’s suggested that sudden give up in this drug may cause discontinuation symptoms (dysphoric mood, irritability, agitation, dizziness, sensory disturbances, and et al.)
• Narrow angle glaucoma
• Agitation, akathisia, agitation, disinhibition, emotional lability, hostility, aggression, depersonalization
• The patient should be reevaluate periodically to ascertain any need for maintenance treatment.
• Interference with Cognitive and Motor Performance >>>Patients should be cautioned about operating hazardous machinery, avoid driving
• Patients with history of drug abuse.
• CNS-Active Drugs: caution is advised.
• Overdose:
• • Symptoms: paresthesia, sleepiness, dizziness, nausea, hot-cold spells.
  • Overdose Management:
    • General measures: Provide adequate airway, oxygenation, and ventilation, monitor cardiac rhythm and vital signs
    • Gastric lavage:
      • Indicated soon after ingestion,
      • Symptomatic patients.
    • Activated charcoal
    • Antidote: No specific antidotes
• Discontinuing Desvenlafaxine:
  • Taper gradually to minimize the risk of discontinuation symptoms >>> No abrupt discontinuation:
    • abrupt discontinuation symptoms: aggression, agitation, anorexia, anxiety, asthenia, confusion, convulsions, impaired coordination and balance, diarrhea, dizziness, dry mouth, dysphoric mood, fasciculation, fatigue, flu-like symptoms, headache, hypomania, insomnia, nausea, nightmares, nervousness, paresthesia, electric shock sensations, sensory disturbances (including shock like electrical sensations), sleep disturbances, somnolence, sweating, tinnitus, vertigo, and vomiting.
• Geriatrics (> 65 years of age): Caution in treating the elderly is advised

• Semap®
• Micefal®
• Asemap®
• Nhwa®

• 1th generation (Typical) anti-psychotics
• Diphenylbutylpiperidine
• Dopamin Antagonist

• Tablet: 20 mg

• Chronic schizophrenia

Pharmacodynamics:

• Mechanisem of action: blocks the postsynaptic dopamine receptor in the mesolimbic dopaminergic system and inhibits the release of hypothalamic and hypophyseal hormones.

Pharmacokinetics:

 Absorption:

• Orally. Peak plasma concentrations after 2 hours.

Distribution:

 Metabolism:

• Enterohepatic

Excretion:

• Urine and faeces (as N-dealkylated metabolite). Elimination half-life: 36 hours (initial), 120 hours (terminal).

Psychoses (Adult):

• Initial dose: 20-60 mg Po (orally) weekly
• Maximum dose: 250 mg Po (orally) once a week in severe or resistant conditions.

• Orthostatic hypotension with MAOIs
• Increase sedation with alcohol, hypnotics, antihistamines, opiates
• Antacids containing aluminum salts may decrease absorption of Penfluridol
• Additive antimuscarinic effects with TCAs
• Reduce bromocriptine‘s ability to reduce serum prolactin
• Amphetamines may increase psychosis
• Inhibit antiparkinsonian effects of levodopa
• Increase risk of extrapyrimidal symptoms with Metoclopramide
• Increase phenytoin levels (phenytoin may reduce penfluridol levels)
• Possible additive effects on QT interval with type 1a antiarrhythmics, TCAs, some quinolone antibiotics (e.g. Moxifloxacin)
• Have additive hypotensive effects with Trazodone
• May increase levels of valproic acid (Enzyme inhibitor effect of Penfluridol).
• Potentially Fatal: May produce neurotoxicity with lithium.
• Food interactions: Avoid valerian, St John’s wort, kava kava, gotu kola => increased risk of CNS depression.

More Frequent:

• Slightly sedative
• Extrapyramidal symptoms: Parkinsonism, rigidity, tremor Akathisia, Tardive Dyskinesiae and pseudo-Parkinsonism.

Less Frequent:

•  Lower threshold for seizures 
• Blurring of vision
• Dry mouth  
• Retention of urine
• Constipation
• Orthostatic hypotension
• Weight gain
• Impaired glucose tolerance
• Allergic skin rashes
• cholestatic jaundice
• Delirium
• Agitation
• Anxiety
• Depression
• Euphoria
• Anorexia
• Constipation
• Diarrhea
• Alopecia
• Amenorrhoea
• Hyperprolactinemia (Leaking milk from breast)
• Hypoglycaemia
• hyponatraemia
• hypersalivation
• Nausea, vomiting
• Bronchospasm
• Venous blood clots, particularly in the legs (the symptoms include swelling, pain and redness in the legs)
• Potentially Fatal side effects: Blood dyscrasias; neuroleptic malignant syndrome; alteration of heart conduction leading to QT prolongation and life threatening arrhythmias.

• MAOIs
• Alcohol, hypnotics, antihistamines, opiates
• Antacids containing aluminum salts
• TCAs
• Hyperprolactinemia due to any cause
• Amphetamines
• Levodopa
• Metoclopramide
• Phenytoin
• Medications cause long Q-T interval: 1a antiarrhythmics, TCAs, some quinolone antibiotics (e.g. Moxifloxacin)
• Trazodone
• valproic acid
• Lithium.
• Valerian, St John’s wort, kava kava, gotu kola

Pregnancy: Category C

Lactation: Not recommended in nursing mother

1. Extremely long elimination half-life and its effects last for many days after single oral dose.

2. Slightly sedative, but often causes extrapyramidal side effects, such as akathisia, dyskinesiae and pseudo-Parkinsonism.

3. Caution in elderlies! do a dose adjustment with close monitoring.

4. Caution in patients with epilepsy!

5. Caution in preexisting cardiac conduction problems; hypokalaemia, hypomagnesemia; hypothyroidism.

6. Use with caution in patients with => liver, heart, kidney diseases

7. Avoid driving and using of machinery while taking Penfuridol => it reduces awareness, sleepiness, dizziness and visual problems associated with the use of this medicine.

8. Caution for Neuroleptic Malignant Syndrome (NMS): hyperpyrexia, muscle rigidity, altered mental status (including catatonic signs), and evidence of autonomic instability (irregular pulse or blood pressure), elevated CPK, myoglobinuria (rhabdomyolysis), and acute renal failure. NMS is potentially fatal, requires intensive symptomatic treatment and immediate discontinuation of neuroleptic treatment.

9. Over-dosage:

• Severe extrapyramidal reactions
• Hypotension (can produce shock like state)
• Sedation
• Treatment: No specific antidote, do a supportive therapy, Heart monitoring, ECG (QT Prolongation), Pulse-Oxymetery, Observe Airway, Breathing, circulation.

10. Caution for Tardive Dyskinesia:

• Rhythmical involuntary movements of the tongue, face, mouth or jaw (e.g. protrusion of tongue, puffing of cheeks, puckering of mouth, chewing movements) Irreversible in some patients in patients treated with neuroleptics with antipsychotic properties and other drugs with substantial neuroleptic activity. The risk of developing tardive dyskinesia may minimize by reducing the dose of the neuroleptic drug used and its duration of administration => anti-Parkinson agents usually do not alleviate the symptoms of this syndrome.

11. Caution in administration of Penfuridol in patients with bone marrow suppression disorders, failures due to any cause => close observation (Complete blood count with differential and absolute neutrophil count in mandatory)

This document is prepared by the “Mental Health for All” team. The general information provided on the Website is for informational purposes only and is not professional medical advice, diagnosis, treatment, or care, nor is it intended to be a substitute therefore. Always seek the advice of your physician or other qualified health provider properly licensed to practise medicine or general healthcare in your jurisdiction concerning any questions you may have regarding any information obtained from this Website and any medical condition you believe may be relevant to you or to someone else. Never disregard professional medical advice or delay in seeking it because of something you have read on this Website. Always consult with your physician or other qualified healthcare provider before embarking on a new treatment, diet, or fitness program. Information obtained on the Website is not exhaustive and does not cover all diseases, ailments, physical conditions, or their treatment.

• ^Pr PIMOZIDE

• Antipsychotic, 1st generation

• Pimozide Tablets USP 2 mg and 4 mg

• Management of the manifestations of chronic schizophrenia in which the main manifestations do not include excitement, agitation or hyperactivity.

• Mechanism of Action:
  • The basic mechanism of action is related to its action on central aminergic receptors.
  • It has a selective ability to block central dopaminergic receptors, although it affects noradrenaline turnover at higher doses.

• Pharmacokinetics
  • Absorption: More than 50%
  • Peak serum level: 6-8 hours
  • Metabolism:
    • Undergo significant first-pass metabolism.
    • Pimozide is extensively metabolized in the liver.
  • Mean elimination half-life: 55 hours.
  • Excretion: kidney

• Adults:
  • Usual Starting Dose: 2 to 4 mg once daily, with weekly increments of 2 to 4 mg until a satisfactory level of therapeutic effect is attained or excessive adverse effects occur.
  • Maintenance Therapy: 6 mg daily
  • Max dose: 20 mg
• Missed Dose:
  • Patient should take the dose as soon as possible and continue with their regular schedule.
  • If it is almost time for the next dose: patient should skip the missed dose and continue with the next scheduled dose.

1. Drugs acting on CNS:
   1. Anesthetics, opiates, alcohol, atropine, organophosphorous, amphetamines.
2. Levodopa
3. Anti-hypertensives
4. Drugs That Inhibit Cytochrome P450:
   1. aprepitant, azole antimycotics, antiviral protease inhibitors, macrolide antibiotics, nefazodone.
5. Drugs That Prolong QT Interval:
   1. Class IA antiarrhythmics (quinidine, procainamide, disopyramide)
   2. Class III antiarrhythmics (amiodarone, sotalol, ibutilide)
   3. Class 1C antiarrhythmics (flecainide, propafenone)
   4. antipsychotics (chlorpromazine, pimozide, haloperidol, droperidol)
   5. antidepressants (fluoxetine, venlafaxine, tricyclic/tetracyclic antidepressants)
   6. opioids (methadone)
   7. macrolide antibiotics and analogues (erythromycin, clarithromycin, telithromycin)
   8. quinolone antibiotics (moxifloxacin, gatifloxacin)
   9. pentamidine
   10. antimalarials (quinine)
   11. azole antifungals (fluconazole, itraconazole, ketoconazole, voriconazole)
   12. domperidone
   13. 5-HT3 antagonists (dolasetron, ondansetron)
   14. tacrolimus
   15. beta-2 adrenoceptor agonists (salmeterol, formoterol)
   16. Lithium
6. Drugs causing electrolyte alteration:
   1. Diuretics (particular those causing hypokalemia.)
   2. Laxatives and enemas
   3. Amphotericin B
   4. High dose corticosteroids
7. SSRI (Selective Serotonin Reuptake Inhibitor) Antidepressants:
   1. sertraline
   2. citalopram
   3. paroxetine
8. Drug-Food Interactions
   1. Grapefruit Juice
9. Drug-Herb Interactions
   1. Betel Nut

• Blood and Lymphatic System Disorders:
  • Blood dyscrasias (agranulocytosis, anemia, aplastic anemia, eosinophilia, granulocytopenia, leukopenia, neutropenia, pancytopenia, and thrombocytopenic purpura), bone marrow failure, disseminated intravascular coagulation, leukocytosis, lymphadenopathy, polycythaemia, and thrombocytopenia.
• Cardiac Disorders:
  • angina pectoris, arrhythmia, coronary atherosclerosis, atrioventricular block, cardiac arrest, cardiac failure, cardiac valve disease, cardio-respiratory arrest, cardiomegaly, coronary artery disease, myocardial infarction, myocardial ischemia, myocarditis, stress cardiomyopathy, torsade de pointes, ventricular tachycardia, ventricular fibrillation.
• Congenital, Familial and Genetic Disorders:
  • Congenital anomaly, congenital hydronephrosis, double ureter, dysmorphism, macrocephaly, microphthalmos, skull malformation, Tourette’s disorder, urinary tract malformation, ventricular septal defect.
• Endocrine Disorder:
  • Increased blood prolactin, hyperglycemia (in patients with pre-existing diabetes), hyperprolactinemia, hyperthyroidism, inappropriate antidiuretic hormone secretion.
• Eye Disorder:
  • Accommodation disorder, glaucoma, oculogyration, blurred vision, visual impairment.
• Gastrointestinal Disorders:
  • Constipation, diarrhea, dry mouth, hemorrhagic enterocolitis, fecal incontinence, intestinal ischemia, pancreatitis, salivary hypersecretion, sub ileus, vomiting.
• General Disorder and Administration Site Conditions:
  • Asthenia, death, drug interaction, face edema, fatigue, hyperthermia, hypothermia, macrosomia, malaise, pyrexia.
• Hepatobiliary Disorders:
  • Abnormal hepatic function, hepatitis, hepatomegaly, liver injury.
• Immune System Disorders:
  • Antiphospholipid syndrome.
• Infections and Infestations:
  • Bacterial infection, bacterial toxemia, bronchitis, bronchopneumonia, pneumonia, pustular rash.
• Injury, Poisoning and Procedural Complications:
  • Accidental exposure, contusion, drug dispensing error, drug toxicity, fall, femoral neck fracture, overdose, wound.
• Investigations:
  • increased blood creatinine phosphokinase, increased blood phosphorus, decreased blood pressure, increased blood pressure, breath sounds, circulating coagulant, increased drug level, abnormal electrocardiogram (repolarization, ST segment depression, T wave inversion, T wave peaked), prolonged electrocardiogram QT interval, abnormal electroencephalogram, decreased hematocrit, decreased hemoglobin, increased hepatic enzyme, decreased red blood cell count, increased red cell distribution width, increased respiratory rate, increased transaminases, increased weight, decreased white blood cell count, increased white blood cell count.
• Metabolism and Nutrition Disorders:
  • Decreased appetite, diabetes mellitus (type I and type II), dyslipidemia, reduced fluid intake, hyper-phagia, hypoglycemia, hypokalemia, hyponatremia, ketoacidosis.
• Musculoskeletal and Connective Tissue Disorders:
  • Arthralgia, muscle rigidity, myalgia, nuchal rigidity, rhabdomyolysis, soft tissue hemorrhage, systemic lupus erythematosus.
• Benign, Malignant and Unspecified Neoplasms (Including Cysts and Polyps):
  • Endometrial cancer, myelodysplastic syndrome.
• Nervous System Disorders:
  • akathisia, altered state of consciousness, bradykinesia, cognitive disorder, cogwheel rigidity, coma, convulsion, dementia, disturbance in attention, dizziness, drooling, dyskinesia, dystonia, epilepsy, extrapyramidal disorder, grand mal convulsion, hemorrhagic cerebral infarction, headache, hypoesthesia, hypo-kinesia, hypoxic-ischemic encephalopathy, loss of consciousness (syncope), lethargy, masked facies, mental retardation, neuroleptic malignant syndrome, parkinsonism, somnolence, stupor, tardive dyskinesia, tremor, unresponsive to stimuli.
• Pregnancy, Puerperium and Prenatal Conditions:
  • Missed abortion, spontaneous abortion.
• Psychiatric Disorder:
  • abnormal behavior, aggression, agitation, apathy, confusional state, decreased activity, delusion, depression, disorientation, drug dependence, euphoric mood, hallucination, insomnia, decreased libido, mutism, psychomotor retardation, restlessness, schizophrenia, self-injurious behavior, sleep disorder, suicide, suicide attempt, withdrawal syndrome.
• Renal and Urinary Disorders:
  • Anuria, glycosuria, hematuria, nephrotic syndrome, renal failure, urinary incontinence, urinary retention.
• Reproductive System and Breast Disorder:
  • Amenorrhea, breast cysts, erectile dysfunction, galactorrhea, gynecomastia.
• Respiratory, Thoracic and Mediastinal Disorders:
  • Asphyxia, bradypnea, dyspnea, hypoxia, lung disorder, oropharyngeal spasm, pulmonary congestion, pulmonary embolism, pulmonary edema, pulmonary thrombosis, respiratory arrest.
• Skin and Subcutaneous Tissue Disorders:
  • Angioedema, hyperhidrosis, photosensitivity reaction, pruritus, rash (exfoliative, erythematous, and popular), skin exfoliation, skin toxicity, toxic skin eruption, urticarial.
• Vascular Disorders:
  • Arteriosclerosis, circulatory collapse, deep vein thrombosis, venous embolism, hematoma, hypertension (orthostatic), phlebitis, shock, thrombosis.

1. Hypersensitive to drug
2. Central nervous system depression
3. Brain damage
4. Comatose states
5. Liver disorders
6. Renal insufficiency
7. Pheochromocytoma
8. Blood dyscrasias
9. Depressive disorders
10. Parkinson’s syndrome
11. congenital long QT syndrome or a family history of this syndrome
12. cardiac arrhythmias or Torsade de Pointes
13. Combination with CYP 3A4 and CYP 2D6 inhibiting drugs:
    1. Azole anti-mycotics, antiviral protease inhibitors, macrolide antibiotics and nefazodone, quinidine.
14. The treatment of simple tics or tics other than those associated with Tourette’s Disorder.
15. Combination with serotonin reuptake inhibitors:
    1. sertraline, paroxetine, citalopram and escitalopram
16. A scheduled regional or spinal anesthesia.

• Pregnancy: Category C
• Lactation: Not recommended in nursing mothers

1. Body Temperature Regulation:
   1. Disruption of the body’s ability to reduce core body temperature >>> Hyperpyrexia might happen
2. Caution about Cardiovascular side effects:
   1. QT prolongation
   2. ventricular arrhythmias (Ventricular tachycardia, ventricular fibrillation)
   3. Sudden death and cardiac arrest (very rare)
   4. Potential for Hypotension
   5. Torsade de Pointes, Risk factors:
      1. female
      2. age 65 years or older
      3. baseline prolongation of the QT/QTc interval
      4. presence of genetic variants affecting cardiac ion channels or
      5. regulatory proteins, especially congenital long QT syndromes
      6. family history of QT prolongation, or sudden cardiac death at <50 years
      7. cardiac disease (e.g., myocardial ischemia or infarction, congestive heart failure, left ventricular hypertrophy, cardiomyopathy, conduction system disease)
      8. history of arrhythmias (especially ventricular arrhythmias, atrial fibrillation, or recent conversion from atrial fibrillation)
      9. electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypocalcemia)
      10. bradycardia (<50 beats per minute)
      11. acute neurological events (e.g., intracranial or subarachnoid hemorrhage, stroke, intracranial trauma)
      12. nutritional deficits (e.g., eating disorders, extreme diets)
      13. diabetes mellitus,
      14. autonomic neuropathy
      15. hepatic dysfunction, renal dysfunction, and/or phenotypic/genotypic poor metabolizers of drug metabolizing enzyme isoforms
   6. ECG should be performed prior to initiation of treatment with pimozide, as well as periodically during treatment.

3. Endocrine and Metabolism
   1. Hyperprolactinemia (cause galactorrhea, gynecomastia, oligo-menorrhea or amenorrhea, and erectile dysfunction.)
   2. Caution in patients with a previously detected breast cancer.
   3. Long-standing hyperprolactinemia causes hypogonadism >>> leads to decreased bone mineral density.
   4. Hyperglycemia:
      1. Diabetic ketoacidosis (DKA) might occur
      2. Patients should have baseline and periodic monitoring of blood glucose and body weight.
4. Gastrointestinal:
   1. Pimozide has a substantial antiemetic effect >>> caution in cases where the suppression of nausea and vomiting might hinder the diagnosis of an underlying physical disorder.
5. Genitourinary;
   1. Caution patient about priapism.
6. Hematologic:
   1. Neutropenia, leukopenia, granulocytopenia, agranulocytosis and anemia might occur >>> complete blood count (CBC) tested should be done prior to starting pimozide.
7. Patient should be cautioned about Venous thromboembolism (VTE)
8. Hepatic/Biliary/Pancreatic:
   1. Caution is advised in patients with liver disease because pimozide is metabolized in the liver.
9. Neurologic
   1. Increased Psychomotor Activity:
      1. Should not be used in the management of chronic schizophrenia with main symptoms of agitation, excitement and anxiety.
   2. Neuroleptic Malignant Syndrome:
      1. Hyperthermia (early sign), generalized muscle rigidity, autonomic instability, and altered consciousness.
   3. Tardive Dyskinesia
   4. Withdrawal Emergent Neurological Signs:
      1. Gradual withdrawal of antipsychotic drugs is recommended
   5. Schizophrenia:
      1. Response to antipsychotic drug treatment may be delayed >>> Gradual withdrawal is advisable.
   6. Extrapyramidal Symptoms
   7. Seizures:
      1. pimozide might lower the convulsive threshold >>> should be used with caution in epileptic patients
   8. Effects on Driving Ability and Use of Machinery:
      1. Patients should be warned of the risks of sedation and advised not to drive or operate machinery during treatment
10. Pediatrics (<18 years of age):
    1. Not recommended for use in the pediatric age group.
11. Geriatrics (≥65 years of age):
    1. Caution should be exercised with the use of pimozide in the elderly
    1. Use in Geriatric Patients with Dementia:
       1. Pimozide is not indicated in elderly patients with dementia.
12. Over dosage:
    1. Symptoms:
       1. Exaggeration of known pharmacologic effects and adverse reactions, extrapyramidal symptoms, cardiac arrhythmias.
    2. Treatment:
       1. No specific antidote for pimozide
       2. Treatment is mainly supportive.

• Haldo®
• Haldol Decanoate®
• Haloperidol La®
• Peridol®
• Aloperidin®
• Bioperidolo®
• Brotopon®
• Dozic®
• Duraperidol (Germany)®
• Einalon S®
• Eukystol®
• Haldol (common tradename in the US and UK)®
• Halosten®
• Keselan®
• Linton®
• Peluces®
• Serenace®
• Sigaperidol®

1th generation (Typical) anti-psychotics

Butyrophenones

Dopamin Antagonist

• Tablet: 0.5mg, 1mg, 2 mg, 5 mg, 10 mg, 20 mg
• Oral Concentrate: 2 mg/mL
• Injectable solution: 50 mg/mL, 100 mg/mL, Ampoule 5 mg/mL, 1 mL

Haloperidol:

Adults: Gilles de la Tourette’s syndrome (Tic disorder), , Schizophrenia

• Bipolar Manic disorder
• Intractable hiccups
• Alcohol induced psychosis (Alcohol induced hallucinations) as adjunctive therapy.
• Acute psychosis: Drug-induced psychosis => LSD, psilocybin, amphetamines, ketamine and phencyclidine.
• Opioid withdrawal symptom management
• Borderline personality disorder (Therapeutic trial)
• Severe Nausea/Vomiting: post operative patients, patients receiving chemotherapy or radiotherapy.
• Chorea form disorders
• Agitation and confusion associated with cerebral sclerosis
• Delirious state: controlling agitation.

Pediatrics Older than 3 years of age: Gilles de la Tourette’s syndrome (Tic disorder), Psychotic disorder, Schizophrenia, Hyperactive disorder (Short-term use)

Haloperidol Lactate:

• Adults:
• Gilles de la Tourette’s Syndrome (Tic disorder)
• Psychotic disorder
• Schizophrenia
• Bipolar Manic disorder
• Intractable hiccups
• Alcohol induced psychosis (Alcohol induced hallucinations) as adjunctive therapy.
• Acute psychosis: Drug-induced psychosis => LSD, psilocybin, amphetamines, ketamine and phencyclidine.
• Opioid withdrawal symptom management
• Borderline personality disorder (Therapeutic trial)
• Severe Nausea/Vomiting: post operative patients, patients receiving chemotherapy or radiotherapy.
• Chorea form disorders
• Agitation and confusion associated with cerebral sclerosis
• Delirious state: controlling agitation.
• Pediatrics: Not FDA approval

Pediatrics: Not FDA approval

Haloperidol Decanoate:

Adults:

• Chronic Schizophrenia
• Bipolar Manic disorder
• Intractable hiccups
• Alcohol induced psychosis (Alcohol induced hallucinations) as adjunctive therapy.
• Acute psychosis: Drug-induced psychosis => LSD, psilocybin, amphetamines, ketamine and phencyclidine.
• Opioid withdrawal symptom management
• Borderline personality disorder (Therapeutic trial)
• Severe Nausea/Vomiting: post operative patients, patients receiving chemotherapy or radiotherapy.
• Chorea form disorders
• Agitation and confusion associated with cerebral sclerosis
• Delirious state: controlling agitation.

Pharmacodynamics:

• Mechanism of action: typical butyrophenone => D2 blocker, Alfa1 Blocker, Antagonist of 5-HT2 receptor, Muscarinic 1 receptor affinity (Anti-cholinergic effect), Histaminic 1 receptor affinity( Anti-histaminic effect)

Pharmacokinetics:

1. Absorption:

• Oral: Bioavailability is 60%-70%. 30-60 minutes in intramuscular- intravenous injection.
• Intramuscular injections: rapidly absorbed – high bioavailability almost 20 minutes.
• Intravenous injections: Bioavailability is 100% in intravenous (IV) injection, and the very rapid onset of action is seen within seconds.

2. Distribution: 90% binds to plasma proteins.

3. Metabolism: Cytochrome p450 in liver (CYP3A4).

4. Excretion: 30% Urine + 15% feces

 Haloperidol (Adult Dose):

• Gilles de la Tourette’s syndrome: Moderate symptoms => 0.5 to 2 mg/ Severe symptoms => 3 to 5 mg (Po) orally2 to 3 times per day (Bid-Tid).
• Psychotic disorder: moderate symptoms => 0.5 to 2 mg / severe symptoms => 3 to 5 mg (Po) orally 2 to 3 times per day (Bid-Tid).
• Schizophrenia: moderate symptoms => 0.5 to 2 mg / severe symptoms 3 to 5 mg (Po) orally 2 to 3 times per day (Bid-Tid).

Haloperidol (Pediatrics dose – Do not use in children less than 3 years of age):

1. Gilles de la Tourette’s syndrome:

Age 3 to 12 years (Weight: 15 to 40 kg):

• Initial dose: lowest possible dose (0.5 mg per day) or weight-based dose (0.05 to 0.075 mg/kg/day) Orally (Po) in 2 to 3 divided doses, whichever is less.
• Incremental dose:5 mg at 5 to 7 day intervals to therapeutic effect.

 Over age 12 years:

• Moderate Symptoms => 0.5- 2 mg Orally (Po) 2 to 3 times per day (Bid-Tid)
• Severe Symptoms => 3-5 mg Orally (Po) 2 to 3 times per day (Bid-Tid).

2. Hyperactive behaviour: (Short term administration- If patient is not responded to non-antipsychotic medications and psychotherapy)

3 to 12 years (weight 15 to 40 kg):

• Initial dose:05 to 0.075 mg/kg/day Orally (Po) in 2 to 3 divided doses (Bid-Tid)
• Incremental dose:5 mg at 5 to 7 day intervals to therapeutic effect
• MAX daily dose: 0.075 mg/kg/day

Over age 12 years:

• Moderate symptoms: 0.5 to 2 mg
• Severe symptoms: 3 to 5 mg orally 2 to 3 times per day (Bid-Tid)

3. Psychotic disorder:

3 to 12 years (weight 15 to 40 kg)=>

• Initial dose:05 mg/kg/day Orally (Po) in 2 to 3 divided doses (Bid-Tid),
• Incremental dose5 mg/day at 5 to 7 day intervals to therapeutic effect
• MAX daily dose15 mg/kg/day

12 years and older =>

• Moderate symptoms:5 to 2 mg
• Severe symptoms: 3 to 5 mg Orally (Po) 2 to 3 times (Bid-Tid)

4. Schizophrenia:

3 to 12 years (weight 15 to 40 kg) =>

• Initial dose:05 mg/kg/day Orally (Po) in 2 to 3 divided doses (Bid-Tid)
• Incremental dose:5 mg/day at 5 to 7 day intervals to therapeutic effect
• MAX daily dose15 mg/kg/day

12 years and older:

• Moderate symptoms:5 to 2 mg 3 to 5 mg
• Severe symptoms: Orally (Po) 2 to 3 times daily (Bid-Tid)

Geriatric and debilitated patients:

• May require higher doses (0.5 to 2 mg 2 to 3 times/day (Bid-Tid)
• Chronic refractory schizophrenia: Initial dose:5 to 1.5 mg/day orally (Po) => Gradually increased to maintenance dose of 2 to 8 mg/day
• Mentally retarded with hyperkinesia: Initial dose:5 to 6 mg/day orally (Po) in divided doses. Gradually increased to maintenance (minimally effective maintenance dose).
• Maximum dose: 15 max/day to achieve control => Decrease to minimally clinically effective dose.

Haloperidol Decanoate:

Adult Dose:

Chronic Schizophrenia: (Two methods recommended)

• Initial dose: stabilized on low daily oral doses (up to 10 mg/day), 10 to 15 times previous daily oral dose IM monthly or every 4 weeks.
• Initial dose: stabilized on high daily oral doses, 20 times previous daily oral dose IM for the first month, then 10 to 15 times previous daily oral dose IM monthly or every 4 weeks,
• MAX initial dose 100 mg

Pediatrics Dose: Not safe in this group

Haloperidol Lactate:

1. Adult Dose:

Gilles de la Tourette’s syndrome:

• Initial dose: 2 to 5 mg IM, may repeat every 4 to 8 hours depending on patient response
• Incremental dose: every 1 hour if needed

Schizophrenia:

• Initial dose: 2 to 5 mg IM, may repeat every 4 to 8 hours depending on patient response
• Incremental dose: every 1 hour if needed

2. Pediatrics Dose: Not safe in this group

Tricyclic antidepressants (Haloperidol is enzyme Enzyme inhibitor)

Carbamazepine (Carbamazepine is Enzyme inducer)

Anti-parkinsonism agents:e.g Levodopa

Amiodarone

Cizapride

Terfenadine

Sotalol

Quinidine

Pimozide

Pentamidine

Procainamide

More frequent:

• Acute dystonia
• Extra pyramidal symptoms – Rigidity (Parkinsonism)
• Akathisia
• Tardive dyskinesia (long term administration)

Less frequent:

• Paralytic ileus
• Priapism
• Seizure
• Sudden cardiac death
• Tardive dyskinesia
• Torsades de pointes
• Prolonged QT interval
• Jaundice
• Hepatitis
• Cholestasis
• Acute hepatic failure
• Liver function test abnormal
• Hypoglycemia
• Hyperglycemia
• Hyponatremia
• Anaphylactic reaction
• Hypersensitivity
• Neutropenia
• Leukopenia
• Thrombocytopania
• Pancytopenia
• Confusional state
• Depression
• Insomnia
• Seizure
• Ventricular fibrillation
• Ventricular tachycardia
• Extrasystoles
• Bronchospasm
• Laryngospasm
• Laryngeal edema
• Dyspnea
• Nausea
• Vomiting
• Leukocytoclastic vasculitis
• Dermatitis exfoliative
• Urticaria
• Photosensitivity reaction
• Rash
• Itchiness
• Increased sweating
• Urinary retention
• Gynecomastia
• Sudden death
• Face edema
• Edema
• Hypothermia
• Hyperthermia
• Injection site abscess
• Anorexia
• Pulmonary embolism
• Tardive dyskinesia
• Cataracts
• Retinopathy
• Neuroleptic malignant syndrome

• Comatose state from any cause
• Known Hypersensitivity to Haloperidol
• Parkinson’s disease
• Central nervous system depression
• Patients with dementia-related psychosis
• Narrow angle glaucoma
• Bone marrow suppression/failure patients
• Leukopenic / Neutropenic patients due to any cause

Pregnancy: Category C

Lactation: Not recommended in nursing mother

1. Haloperidol Decanoate is in a sesame seed oil base and must not be given intravenously (Absolute contraindication). => Only deep intramuscular injection (21G needle) into the gluteal region. Maximum recommended volume is 3 milliliters per injection site.

2. Do NOT administer Haloperidol Lactate intravenously (Relative contraindication). Although it is recommended not to inject intravenously (Not FDA approval- off label), some centers (Coronary care unites) administer it:

• Initial infusion doses of 2 to 25 milligrams per hour (Initial bolus dose of 10 milligrams followed by continuous infusion beginning as 10 milligrams per hour is recommended.)
• Maximum infusion rate: 40mg/hr
• Caution: administer Haloperidol Lactate intravenous continuous dose in patients not effectively managed by first line sedatives and in those attempted reversal of the cause of agitation has been unsuccessful.

3. Switching from injectable to oral haloperidol:

the first oral dose should be administered within 12- 24 hours following the last parenteral dose.

4. Caution is advised in patients with phaeochromocytoma and conditions predisposing to epilepsy such as alcohol withdrawal and brain damage. Haloperidol may lower the convulsive threshold.

5. Caution in administration of Haloperidol in patients with bone marrow suppression disorders, failures due to any cause => close observation (Complete blood count with differential and absolute neutrophil count in mandatory)

6. Caution in patients with Cognitive diseases => Alzheimer disease. May prone the patient to pneumonia.

7. Caution for Tardive Dyskinesia: 

• Rhythmical involuntary movements of the tongue, face, mouth or jaw (e.g. protrusion of tongue, puffing of cheeks, puckering of mouth, chewing movements)  Irreversible in some patients in patients treated with neuroleptics with antipsychotic properties and other drugs with substantial neuroleptic activity. The risk of developing tardive dyskinesia may minimize by reducing the dose of the neuroleptic drug used and its duration of administration => anti-Parkinson agents usually do not alleviate the symptoms of this syndrome.

8. Do not do abrupt discontinuation => gradual withdrawal of antipsychotic drugs will decrease the incidence of withdrawal emergent neurological signs.

9. Administer cautiously to patients with severe impairment of liver or kidney

10. Haloperidol may interfere with the anticoagulant properties of phenindione. Possibility should be kept in mind of a similar effect occurring when Haloperidol is used with other anticoagulants.

11. Haloperidol may antagonize the action of adrenaline and other sympathomimetic agents and reverse the blood-pressure-lowering effects of adrenergic-blocking agents such as guanethidine.

 12. Caution in concomitant use with methyldopa: Enhanced CNS effects have seen.

13. Caution in concomitant use with Tricyclic antidepressants: Haloperidol inhibits the metabolization of Tricyclic antidepressants => increasing plasma levels of these drugs => increased tricyclic antidepressant toxicity (anticholinergic effects, cardiovascular toxicity, lowering of seizure threshold).

14. Caution in concomitant use with Carbamazepine (Carbamazepine has enzyme inducer effect) => May cause significant reduction of plasma level of Haloperidol => do a dose adjustment.

15. Caution in concomitant use with Levodopa (Anti-parkinsonism agent) => it may have a synergistic effect! (Increase extrapyramidal symptoms: akathisia, Tardive dyskinesia, dystonia, hyperreflexia, rigidity, opisthotonos, and occasionally, oculogyric crisis):

• Administration of an anti-Parkinson agent is usually, but not always effective in preventing or reversing neuromuscular reactions associated with Haloperidol Decanoate.

16. Watch out for Severe neurotoxicity (rigidity, inability to walk or talk) may occur in patients with thyrotoxicosis who are also taking antipsychotic medications: Haloperidol.

17. Neuroleptic drugs (Anti-psychotics including Haloperidol) elevate prolactin levels; the elevation persists during chronic administration. => galactorrhea, amenorrhea, gynecomastia and impotence may occur.

18. Caution for Neuroleptic Malignant Syndrome (NMS): hyperpyrexia, muscle rigidity, altered mental status (including catatonic signs), and evidence of autonomic instability (irregular pulse or blood pressure), elevated CPK, myoglobinuria (rhabdomyolysis), and acute renal failure. NMS is potentially fatal, requires intensive symptomatic treatment and immediate discontinuation of neuroleptic treatment:

• Hyperpyrexia and heat stroke, not associated with the above symptom complex, has also been reported.

19. Over-dosage:

• Symptoms: Severe extrapyramidal reactions, Hypotension (can produce shock like state), Sedation
• Treatment: No specific antidote, do a supportive therapy, Heart monitoring, ECG (QT Prolongation), Pulse-Oxymetery, Observe Airway, Breathing, circulation.