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Posted - 05/13/2005 :  15:18:17  Show Profile  Visit Administrator's Homepage  Reply with Quote  Reply to Topic
Synopsis:

Clozapine is an antipsychotic medication that is licenced for the treatment of Schizophrenia. It is also effective in the acute treatment of mania and mixed episodes of Bipolar I Disorder. It is also used in the maintenance treatment of Bipolar I Disorder (but there is little research supporting this).

Clozapine often increases weight. There is a FDA warning that it (infrequently) causes life-threatening agranulocytosis. It sometimes causes seizures or increases the risk of diabetes mellitus. Clozapine has a well-earned reputation for being effective in patients that are refractory to other antipsychotic medications.



INFORMATION FOR PATIENTS

What Is Clozapine (CLOZARIL) And What Is It Used For?

Clozapine is a drug for the treatment of symptoms of schizophrenia or mania in patients who do not respond to, or who experience serious side effects with other drugs used for the same purpose.

Clozapine can only be taken if prescribed by a doctor.

If you have any questions about how clozapine works or why this medicine has been prescribed to you, ask your doctor.

What Should Be Borne In Mind About Clozapine (CLOZARIL)? Why Is The Testing Of Your Blood By Your Doctor Necessary?

In rare instances (approximately 0.7% of cases), clozapine can cause a suppression of white blood cells, necessary to help the body fight infection. Because this condition is potentially life-threatening, it is important to have regular blood testing done. To ensure that the required blood tests are performed, clozapine is only available through a special program.

Blood testing must be done weekly during the first 26 weeks of treatment with clozapine, because the risk for developing a deficiency of white blood cells is highest during this initial period. Thereafter, your doctor will evaluate with you the possibility of limiting blood checks to 2-week intervals, depending on your health condition. Regular blood testing must be done for as long as you are taking clozapine.

In addition, you should consult your doctor immediately at the first signs of a cold, flu-like symptoms, fever, sore throat, or any other signs of infection, as well as weakness or a general feeling of unwellness. The doctor may check your blood cell count and take further measures if necessary.

When Should Clozapine (CLOZARIL) Not Be Used?

If you are allergic to clozapine or any of the ingredients of clozapine

If you are unable to undergo regular blood tests

If you have ever been diagnosed as having a low number of white blood cells, except if this was following a treatment for cancer

If you suffer or have ever suffered from bone marrow disease or disease affecting blood cell formation

If you have liver, kidney or heart problems (e.g. myocarditis, cardiomyopathy, heart failure)

If you suffer from uncontrolled epilepsy

If you have problems with alcohol or drug abuse

If you suffer or have ever suffered from severe constipation, obstruction of the bowel or any other condition which has affected your large bowel

If any of the above applies to you, tell your doctor before you take clozapine.

When Taking Clozapine (CLOZARIL), What Particular Precautions Are Recommended?

It is essential to inform your doctor if you suffer from enlargement of the prostate, history of seizures, glaucoma (a condition in which the pressure of fluid in the eye is generally too high), diabetes, allergy, or any other serious medical condition.

You should inform your physician immediately if you develop persistent tachycardia (rapid heart rate) at rest accompanied by other signs and symptoms of heart failure (e.g. chest pain, shortness of breath, swelling of the ankles and feet, or arrhythmias (abnormal heart rhythms). Other symptoms which you may also experience include fatigue, flu-like symptoms, fever that is otherwise unexplained, hypotension (low blood pressure) and/or raised jugular venous pressure (bulging neck veins when sitting or standing). You should contact your physician before discontinuing any medication. (Reference: Canadian Public Advisory, dated January 18, 2002, regarding clozapine cardiotoxicity).

Due to the risk of convulsions during clozapine treatment, you should avoid activities where a sudden loss of consciousness could cause risk to yourself or others (e.g., driving, using machines, swimming, climbing).

Tell your doctor or pharmacist what your coffee intake is and if you smoke. Abrupt changes in your habits may change the effect of clozapine.

Clozapine may intensify the effects of alcohol, sleeping pills, tranquilizers and anti-allergy medicines. You should inform your doctor before taking any other medications (including the ones you may buy without a doctor's prescription).

Other medicines which may change the way clozapine works include, for instance, certain antibiotics, medicines used to treat depression, convulsions or ulcers of the stomach and certain drugs effective against fungal or viral infections.

Clozapine may lower your blood pressure, especially at the start of treatment. This may result in lightheadedness or fainting.

Should Clozapine (CLOZARIL) Be Taken During Pregnancy Or Breast-Feeding?

Clozapine should only be taken during pregnancy if your doctor specifically prescribes it. Therefore, you should consult your doctor if you are or intend to become pregnant.

As CLOZARIL can pass into breast milk, mothers receiving clozapine should not breast-feed.

How Should Clozapine (CLOZARIL) Be Taken?

The dosage in each individual case is decided by the doctor according to the severity of the disease.

For the treatment to be successful, you must follow exactly your doctor's dosage instructions, and under no circumstances should you take more or less than the prescribed dose. If you think the dosage is too weak or too strong, you should discuss this matter with your doctor.

Treatment is usually started with one half of a 25 mg tablet once or twice on the first day. Your doctor will then gradually increase your dose, until the ideal dose for you is established.

Your treatment will continue with a daily dose of clozapine between 300 and 450 mg. Some people may require doses up to a maximum of 900 mg per day.

If you miss a dose of clozapine, and remember within 2 hours, take the dose right away. Otherwise, skip the missed dose and continue with your regular dosing schedule. Do not take double doses. If you have stopped taking clozapine for more than 2 days, do not restart taking the drug, but contact your doctor for dosing instructions.

What Are The Possible Side Effects Of Clozapine (CLOZARIL)?

Tell your doctor or pharmacist as soon as possible if you get unexpected symptoms while you are using clozapine, even if you do not think that they are connected with the medicine.

Some effects could be serious:

  • fast and irregular heart beat that persists when you are at rest, possible accompanied by shortness of breath and swelling of the feet or legs


  • signs of infection such as fever, severe chills, sore throat or mouth ulcers. CLOZARIL can reduce the number of white cells in your blood, and lead to a higher sensitivity to infection.


  • feeling sick, vomiting and/or loss of appetite


  • excessive thirst, dry mouth and passing large amounts of urine may be signs of high sugar levels in the blood
If you experience any of these, tell your doctor immediately.

The most common side effects are drowsiness, dizziness, a rapid heart beat, constipation and increased production of saliva.

Other possible side effects include: headache, tremor, increase or decrease in blood pressure, syncope, fainting, sweating, weight gain, problems in passing or retaining urine. Check with your doctor if constipation gets worse.

What Else Should Be Borne In Mind?

Like all medicines, clozapine should be kept out of the reach of children.



INFORMATION FOR PHYSICIANS

(Note To Patients: Clozapine is usually well-tolerated and safe. However, if you lack medical training, reading the following detailed information may leave you with the false impression that clozapine is an unsafe medication - which it definitely is not. Clozapine has some rare side-effects that could be harmful; hence its use must be regularly medically supervised. If the following detailed information confuses you, please consult your doctor or pharmacist.)

Indications

CLOZARIL (clozapine) is indicated in the management of symptoms of treatment-resistant schizophrenia. In controlled clinical trials, clozapine was found to improve both positive and negative symptoms.

Due to the significant risk of agranulocytosis and seizure associated with its use, clozapine should be limited to treatment-resistant schizophrenic patients who are non-responsive to, or intolerant of, conventional antipsychotic drugs. Non-responsiveness is defined as the lack of satisfactory clinical response, despite treatment with appropriate courses of at least 2 marketed chemically-unrelated antipsychotic drugs. Intolerance is defined as the inability to achieve adequate benefit with conventional antipsychotic drugs because of dose-limiting, intolerable adverse effects.

Because of the significant risk of agranulocytosis and seizure, events which both present a continuing risk over time, the extended treatment of patients failing to show an acceptable level of clinical response to clozapine should ordinarily be avoided. In addition, the need for continuing treatment in patients exhibiting beneficial clinical responses should be periodically re-evaluated.

Clozapine can be used only if regular hematological examinations can be guaranteed.

CLOZARIL is available only through a distribution system that ensures: weekly or every-2-week hematological testing prior to the dispensing of the next period's supply of CLOZARIL

Contraindications

CLOZARIL (clozapine) is contraindicated in patients with myeloproliferative disorders, a history of toxic or idiosyncratic agranulocytosis or severe granulocytopenia (with the exception of granulocytopenia/agranulocytosis from previous chemotherapy). [Clozapine should not be used simultaneously with other agents known to suppress bone marrow function.]

CLOZARIL is also contraindicated in patients with active liver disease associated with nausea, anorexia, or jaundice; progressive liver disease; hepatic failure.

Other contraindications include severe CNS depression or comatose states, severe renal or cardiac disease (e.g., myocarditis), paralytic ileus, uncontrolled epilepsy, and previous hypersensitivity to clozapine or any other components of CLOZARIL.

CLOZARIL is also contraindicated in patients unable to undergo blood tests.

Occupational Hazards

Interference with Cognitive and Motor Performance: Because of the potential for initial sedation, CLOZARIL may impair mental and/or physical abilities especially during the first few days of therapy. The recommendation for gradual dose escalation should be carefully adhered to and patients should be cautioned about activities requiring alertness (e.g., driving, operating machinery, swimming, climbing, etc.) [see Dosage].

Drug Interactions

CLOZARIL may enhance the central effects of alcohol, MAO inhibitors, CNS depressants including narcotics, antihistamines and benzodiazepines, as well as the effects of anticholinergic and antihypertensive agents.

Caution is advised with patients who are receiving (or have recently received) benzodiazepines or other psychotropic drugs, as these patients may have an increased risk of circulatory collapse accompanied by respiratory and/or cardiac arrest.

Owing to its anti-alpha-adrenergic properties, CLOZARIL may reduce the blood pressure increasing effect of norepinephrine or other predominantly alpha-adrenergic agents and reverse the pressor effect of epinephrine.

CLOZARIL should not be used with other agents, such as carbamazepine, having a known potential to suppress bone marrow function. In particular, the concomitant use of long-acting depot antipsychotic drugs should be avoided because these medications, which may have the potential to be myelosuppressive, cannot be rapidly removed from the body.

Concomitant use of valproic acid with CLOZARIL may alter the plasma levels of clozapine. Rare but serious reports of seizures, including onset of seizures in nonepileptic patients, and isolated cases of delirium where CLOZARIL was coadministered with valproic acid have been reported. These effects are possibly due to a pharmacodynamic interaction, the mechanism of which has not been determined.

Substantial elevation of the plasma concentration of clozapine has been reported in patients receiving the drug in combination with fluvoxamine. Smaller elevations in clozapine plasma concentrations have also been reported in patients receiving the drug in combination with other selective serotonin re-uptake inhibitors (SSRIs) such as paroxetine, sertraline and fluoxetine.

The plasma concentration of clozapine is increased by caffeine intake and decreased by nearly 50% following a 5-day caffeine-free period.

Concomitant administration of drugs known to induce cytochrome P450 enzymes may decrease the plasma levels of clozapine:

Drugs known to induce the activity of 3A4 and with reported interactions with clozapine include, for instance, carbamazepine, phenytoin and rifampin.

Known inducers of 1A2 include, for instance, omeprazole and cigarette smoking. In cases of sudden smoking cessation, the plasma clozapine concentration may be increased, thus leading to an increase in adverse effects.

Children and Breast-Feeding

Safety and efficacy in children below age 16 have not been established. Patients should not breast-feed an infant if they are taking CLOZARIL.

Geriatrics

Orthostatic hypotension can occur with CLOZARIL treatment and there have been rare reports of tachycardia, which may be sustained, in patients taking clozapine. Elderly patients, particularly those with compromised cardiovascular function, may be more susceptible to these effects.

Elderly patients may also be particularly susceptible to the anticholinergic effects of clozapine such as urinary retention and constipation.



Adverse Effects

The most serious adverse reactions experienced with CLOZARIL (clozapine) are agranulocytosis, seizure, cardiovascular effects and fever (see Warnings and Precautions). The most common side effects are drowsiness, hypersalivation, tachycardia and sedation.

Adverse Reactions Associated with Discontinuation of Treatment
Sixteen percent of 1080 patients who received (clozapine) in premarketing clinical trials discontinued treatment due to an adverse event, including both those that could be reasonably attributed to (clozapine) treatment and those that might more appropriately be considered intercurrent illness. The more common events considered to be causes of discontinuation included: CNS, primarily drowsiness/sedation, seizures, dizziness/syncope; cardiovascular, primarily tachycardia, hypotension and ECG changes; gastrointestinal, primarily nausea/vomiting; hematologic, primarily leukopenia/granulocytopenia/agranulocytosis; and fever. None of the events enumerated accounts for more than 1.7% of all discontinuations attributed to adverse clinical events.

Commonly Observed Adverse Reactions
Adverse events observed in association with the use of (clozapine) in clinical trials at an incidence of greater than 5% were: central nervous system complaints, including drowsiness/sedation, dizziness/vertigo, headache and tremor; autonomic nervous system complaints, including salivation, sweating, dry mouth and visual disturbances; cardiovascular findings, including tachycardia, hypotension and syncope; and gastrointestinal complaints, including constipation and nausea; and fever. Complaints of drowsiness/sedation tend to subside with continued therapy or dose reduction. Salivation may be profuse, especially during sleep, but may be diminished with dose reduction.

Incidence in Clinical Trials
Table 1 enumerates adverse events that occurred at a frequency of 1% or greater among (clozapine) patients who participated in clinical trials. These rates are not adjusted for duration of exposure.

Table 1: Treatment-Emergent Adverse Experience Incidence Among Patients Taking Clozapine in Clinical Trials (N=842) (Percentage of Patients Reporting)

CNS
Drowsiness/Sedation 39%
Dizziness/Vertigo 19%
Headache 7%
Tremor 6%
Syncope 6%
Disturbed Sleep/Nightmares 4%
Restlessness 4%
Hypokinesia/Akinesia 4%
Agitation 4%
Seizures (convulsions)3%
Rigidity 3%
Akathisia 3%
Confusion 3%
Fatigue 2%
Insomnia 2%
Hyperkinesia 1%
Weakness 1%
Lethargy 1%
Ataxia 1%
Slurred Speech 1%
Depression 1%
Epileptiform Movements/Myoclonic Jerks 1%
Anxiety 1%
Cardiovascular
Tachycardia 25%
Hypotension 9%
Hypertension 4%
Chest Pain/Angina 1%
ECG Change/Cardiac Abnormality 1%
Gastrointestinal
Constipation 14%
Nausea 5%
Abdominal Discomfort/Heartburn 4%
Nausea/Vomiting 3%
Vomiting 3%
Diarrhea 2%
Liver Test Abnormality 1%
Anorexia 1%
Urogenital
Urinary Abnormalities 2%
Incontinence 1%
Abnormal Ejaculation 1%
Urinary Urgency/Frequency 1%
Urinary Retention 1%
Autonomic Nervous System
Salivation 31%
Sweating 6%
Dry Mouth 6%
Visual Disturbances 5%
Integumentary (Skin)
Rash 2%
Musculoskeletal
Muscle Weakness 1%
Pain (back, neck, legs) 1%
Muscle Spasm 1%
Muscle Pain, Ache 1%
Respiratory
Throat Discomfort 1%
Dyspnea, Shortness of breath 1%
Nasal Congestion 1%
Hemic/Lymphatic
Leukopenia/Decreased WBC/Neutropenia 3%
Agranulocytosis 1%
Eosinophilia 1%
Miscellaneous
Fever 5%
Weight Gain 4%
Tongue Numb/Sore 1%

a. Events reported by at least 1% of clozapine patients are included.
b. Rate based on population of approximately 1700 exposed during premarket clinical evaluation of clozapine.


Adverse Events Observed During the InterSePT Study
Adverse events reported during the InterSePT study were consistent with the known safety profiles for clozapine and olanzapine. The 10 most frequently reported adverse events in the Clozaril treatment group were: salivary hypersecretion, somnolence, weight increase, anxiety, depression, dizziness (excluding vertigo), psychotic disorder, suicidal ideation, constipation, and insomnia.

Other Events Observed During the Premarketing Evaluation of CLOZARIL (clozapine)
This section reports additional, less frequent adverse events which occurred among the patients taking clozapine in clinical trials. Various adverse events were reported as part of the total experience in these clinical studies; a causal relationship to clozapine treatment cannot be determined in the absence of appropriate controls in some of the studies. Table 1 enumerates adverse events that occurred at a frequency of at least 1% of patients treated with clozapine. The list below includes all additional adverse experiences reported as being temporally associated with the use of the drug which occurred at a frequency less than 1%, enumerated by organ system.

Central Nervous System
loss of speech, amentia, tics, poor coordination, delusions/hallucinations, involuntary movement, stuttering, dysarthria, amnesia/memory loss, histrionic movements, libido increase or decrease, paranoia, shakiness, Parkinsonism, and irritability.

Cardiovascular
edema, palpitations, phlebitis/thrombophlebitis, cyanosis, premature ventricular contraction, bradycardia, and nose bleed; ischemic changes, arrhythmias, myocardial infarction, and sudden death.

Gastrointestinal
abdominal distention, gastroenteritis, rectal bleeding, nervous stomach, abnormal stools, hematemesis, gastric ulcer, bitter taste, and eructation.

Urogenital
dysmenorrhea, impotence, breast pain/discomfort, and vaginal itch/infection.

Autonomic Nervous System
numbness, polydypsia, hot flashes, dry throat, and mydriasis.

Integumentary (Skin)
pruritus, pallor, eczema, erythema, bruise, dermatitis, petechiae, and urticaria.

Musculoskeletal
twitching and joint pain.

Respiratory
coughing, pneumonia/pneumonia-like symptoms, rhinorrhea, hyperventilation, wheezing, bronchitis, laryngitis, and sneezing.

Hemic and Lymphatic System
anemia and leukocytosis.

Miscellaneous
chills/chills with fever, malaise, appetite increase, ear disorder, hypothermia, eyelid disorder, bloodshot eyes, and nystagmus.

Overdose

For management of a suspected drug overdose, you should contact your regional Poison Control Centre.



Dosage

CLOZARIL (clozapine) treatment must be initiated on an in-patient basis or in an out-patient setting where medical supervision is available and vital signs can be monitored for a minimum of 6 to 8 hours after the initial 2 to 3 doses.

When treatment is initiated in out-patients, special caution is advised in patients who are receiving benzodiazepines or other psychotropic drugs as these patients may have an increased risk of circulatory collapse accompanied by respiratory and/or cardiac arrest (see Precautions: Drug Interactions). Extra caution is advised in patients with cardiovascular disease or a history of seizures (see Warnings).

CLOZARIL is restricted to patients who have a normal white blood cell (WBC) count and differential cell (DC) count and in whom a WBC count and DC count can be carried out at least weekly for the first 26 weeks of treatment with clozapine and at least at 2-week intervals thereafter{‡The change from a weekly to a “once every 2 weeks” schedule should be evaluated on an individual patient basis after 26 weeks of treatment. This decision should be made based upon the clinical judgment of the treating physician, and if he/she deems it appropriate, a consulting hematologist, as well as the patient's willingness to pursue a given frequency of blood monitoring. In turn, the clinical evaluation should take into consideration possible factors that would place the patient in a higher risk group, as well as the hematological profile of the patient during the first 26 weeks of treatment. Weekly hematological testing should be resumed for an additional 6 weeks if therapy is disrupted for more than 3 days. If clozapine is interrupted for 4 weeks or longer, weekly monitoring is required for an additional 26 weeks.}. Monitoring must continue for as long as the patient is on the drug, as well as for at least 4 weeks after discontinuation of treatment.

CLOZARIL is available only through a distribution system that requires weekly or every-2-week hematological testing prior to the delivery of the next period's supply of medication.

The dosage of clozapine must be adjusted individually. For each patient the lowest effective dose should be used.

Initial Dose: On the first day, CLOZARIL (clozapine) should be given at a 12.5 mg dose (one-half of a 25 mg tablet) once or twice, followed by one or two 25 mg tablets on the second day. If well tolerated, the dosage may be increased in daily increments of 25 to 50 mg, achieving a target dose of 300 to 450 mg/day by the end of 2 weeks. Subsequent dosage increases should be made no more than once or twice weekly, in increments not to exceed 100 mg. Cautious titration and a divided dosage schedule are necessary to minimize the risks of hypotension, seizure and sedation.

Switching from Previous Neuroleptics: When CLOZARIL therapy is initiated in a patient undergoing oral neuroleptic therapy, it is generally recommended that the other neuroleptic should first be discontinued by tapering the dosage downwards. Once the neuroleptic is completely discontinued for at least 24 hours, CLOZARIL treatment can be started as described above. It is generally recommended that CLOZARIL should not be used in combination with other neuroleptics.

Therapeutic Dose Range: In most patients, antipsychotic efficacy can be expected within the therapeutic range of 300 to 600 mg/day in divided doses. The total daily dose may be divided unevenly, with the larger portion at bedtime.

Since improvement may be gradual, continued therapeutic response can be expected beyond the first month of treatment.

Maximum Dose: Occasionally, patients may require doses higher than 600 mg/day to obtain an acceptable therapeutic response. Because of the possibility of increased adverse reactions (particularly seizures) at daily doses of 600 mg and higher, the decision to treat in the range of 600 to 900 mg/day must be taken prudently. Patients must be given adequate time to respond to a given dose level before escalation to a higher dose is contemplated. The maximum dose of 900 mg/day should not be exceeded.

Maintenance Dose: After achieving maximum therapeutic benefit, many patients can be maintained effectively at lower doses. Careful downward titration is recommended to the level of 150 to 300 mg/day in divided doses. At daily doses not exceeding 200 mg, a single administration in the evening may be appropriate.

Discontinuation of Therapy: In the event of planned termination of CLOZARIL therapy, gradual reduction in dose is recommended over a 1 to 2 week period. However, should a patient's medical condition require abrupt discontinuation (e.g., severe leukopenia, , cardiovascular toxicity), the patient should be carefully observed for the recurrence of psychotic symptoms and symptoms related to cholinergic rebound such as headache, nausea, vomiting and diarrhea.

Re-initiation of Treatment in Patients Previously Discontinued: CLOZARIL therapy must not be resumed in:
  • Patients who have been discontinued from treatment due to neutropenia (ANC<1.5 x 109/L) or severe leukopenia (WBC <2.0 x 109/L, i.e. Non-rechallengeable Status)


  • Patients with clozapine-induced myocarditis
When restarting patients who have had even a brief interval off CLOZARIL, i.e., 2 days or more since the last dose, it is recommended that treatment be re-initiated with 12.5 mg (one half of a 25 mg tablet) once or twice on the first day (see Dosage for hematological testing conditions). If that dose is well tolerated, it may be feasible to titrate patients back to a therapeutic dose more quickly than is recommended for initial treatment.

Certain additional precautions seem prudent when re-initiating treatment. The mechanisms underlying some of the CLOZARIL-induced adverse reactions are unknown. It is conceivable that re-exposure of a patient might enhance the risk of an untoward event's occurrence and increase its severity. Such phenomena, for example, occur when immune mediated mechanisms are responsible. Therefore, any patient who has previously experienced respiratory or cardiac arrest with initial dosing, but was then able to be successfully titrated to a therapeutic dose, should be re-titrated with extreme caution after even 24 hours of discontinuation.

Note: This information is from a Canadian source. There can be differences in indications and warnings for this drug in other countries.

Phil Long M.D.
Administrator
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pharmacistdan2005
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Posted - 05/20/2005 :  15:03:55  Show Profile  Reply with Quote  Reply to Topic
Important fact about this drug:

Clozaril is not a cure.

The most feared side effect is agranulocytosis, a dangerous drop in the number of a certain kind of white blood cell. Symptoms include fever, lethargy, sore throat, and weakness. If not caught in time, agranulocytosis can be fatal. That is why all people who take Clozaril must have a blood test every week. About 1 percent develop agranulocytosis and must stop taking the drug.

Seizures are another potential side effect, occurring in some 5 percent of people who take Clozaril. The higher the dosage, the greater the risk of seizures.


More common side effects may include:
Abdominal discomfort, agitation, confusion, constipation, disturbed sleep, dizziness, drowsiness, dry mouth, fainting, fever, headache, heartburn, high blood pressure, inability to sit down, loss or slowness of muscle movement, low blood pressure, nausea, nightmares, rapid heartbeat and other heart conditions, restlessness, rigidity, salivation, sedation, sweating, tremors, vertigo, vision problems, vomiting, weight gain

Less common side effects may include:
Anemia, angina (severe, crushing chest pain), anxiety, appetite increase, blocked intestine, blood clots, bloodshot eyes, bluish tinge in the skin, breast pain or discomfort, bronchitis, bruising, chest pain, chills or chills and fever, constant involuntary eye movement, coughing, delusions, depression, diarrhea, difficult or labored breathing, difficulty swallowing, dilated pupils, disorientation, dry throat, ear disorders, ejaculation problems, excessive movement, eyelid disorder, fast, fluttery heartbeat, fatigue, fluid retention, frequent urination, glaucoma (high pressure in the eye), hallucinations, heart problems, hives, hot flashes, impacted stool, impotence, inability to fall asleep or stay asleep, inability to hold urine, inability to urinate, increase or decrease in sex drive, involuntary movement, irritability, itching, jerky movements, joint pain, lack of coordination, laryngitis, lethargy, light-headedness (especially when rising quickly from a seated or lying position), loss of appetite, loss of speech, low body temperature, memory loss, muscle pain or ache, muscle spasm, muscle weakness, nosebleed, numbness, pain in back, neck, or legs, painful menstruation, pallor, paranoia, pneumonia or pneumonia-like symptoms, poor coordination, rapid breathing, rash, runny nose, shakiness, shortness of breath, skin inflammation, redness, scaling, slow heartbeat, slurred speech, sneezing, sore or numb tongue, speech difficulty, stomach pain, stuffy nose, stupor, stuttering, swollen salivary glands, thirst, throat discomfort, tics, twitching, urination problems, vaginal infection, vaginal itch, a vague feeling of being sick, weakness, wheezing, yellow skin and eyes.
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MKultra
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Posted - 05/20/2005 :  19:33:03  Show Profile  Reply with Quote  Reply to Topic
After about 6 months or less the blood work is every other week.
One vile and not that bad.. beats a needle in the hip for those that are on injections
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John_WSDC
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Posted - 03/28/2007 :  21:12:26  Show Profile  Reply with Quote  Reply to Topic
Your comments are very helpful. Thanks!<x113d50e0>
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warbird
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Posted - 02/04/2021 :  06:42:41  Show Profile  Reply with Quote  Reply to Topic
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warbird
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Posted - 03/01/2021 :  07:35:00  Show Profile  Reply with Quote  Reply to Topic
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warbird
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43969 Posts

Posted - 05/14/2021 :  01:39:22  Show Profile  Reply with Quote  Reply to Topic
http://audiobookkeeper.ru/book/1576

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warbird
Super Incredible Member (10000+ posts)

43969 Posts

Posted - 05/14/2021 :  01:41:43  Show Profile  Reply with Quote  Reply to Topic
http://eyesvision.ru/eyesight/26

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warbird
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Posted - 05/14/2021 :  01:44:04  Show Profile  Reply with Quote  Reply to Topic
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warbird
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43969 Posts

Posted - 05/14/2021 :  01:46:25  Show Profile  Reply with Quote  Reply to Topic
http://gadwall.ru/t/132239

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warbird
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43969 Posts

Posted - 05/14/2021 :  01:48:46  Show Profile  Reply with Quote  Reply to Topic
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warbird
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43969 Posts

Posted - 05/14/2021 :  01:51:08  Show Profile  Reply with Quote  Reply to Topic
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warbird
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Posted - 05/14/2021 :  01:53:35  Show Profile  Reply with Quote  Reply to Topic
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warbird
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Posted - 05/14/2021 :  01:55:56  Show Profile  Reply with Quote  Reply to Topic
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warbird
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43969 Posts

Posted - 05/14/2021 :  01:58:20  Show Profile  Reply with Quote  Reply to Topic
http://gascautery.ru/t/752786

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warbird
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43969 Posts

Posted - 05/14/2021 :  02:00:46  Show Profile  Reply with Quote  Reply to Topic
http://gasreturn.ru/t/810810

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