Posted by Sunnely on March 8, 2001, at 20:22:04
In reply to Ziprasidone - available now, posted by Chris A. on March 8, 2001, at 15:43:15
Chris,
Although ziprasidone (Geodon), the newest atypical antipsychotic drug, may be effective in a number of psychiatric disorders aside from schizophrenia, there are important things one should know before taking this drug.
To go back in time, ziprasidone was expected to be released in the fall of 1998. However, Pfizer, the manufacturer, received notification from the US FDA in the summer of 1998 indicating that approval of ziprasidone would be delayed. The primary reason for this non-approval was apparently safety concerns related to potential heart side effects, specifically prolongation of the QTc interval, which has become a controversial issue for new antipsychotics. (Note: Prolongation of QTc on electrocardiogram or ECG is considered a "harbinger" for potentially serious heart beat irregularity ["torsades de pointes"], which could lead to sudden death. Sertindole or Serlect, a very promising atypical antipsychotic did not make it in the US market due to concerns of prolonged QTc. Drugs such as Seldane, Hismanal, and Propulsid, which have been associated with prolonged QTC, "torsades" and sudden deaths have been voluntarily removed from the US market.)
Pfizer did a study directly comparing the QTc prolonging effect of ziprasidone with several other antipsychotic drugs (Risperdal, Zyprexa, Seroquel, and Haldol). The mean increase in QTc from baseline for ziprasidone ranged from approximately 9 to 14 msec (milliseconds) greater than the comparator drugs, but was 14 msec less than the prolongation observed for thioridazine (Mellaril). (Note: Because of this finding, Mellaril got clocked. Subsequently, the FDA required that a "black box" warning be included in the package insert of Mellaril indicating the significant risk of prolonged QTc, "torsades" and sudden deaths. Its clinical indication was also restricted only to schizophrenia and not a first-line antipsychotic.)
In the placebo controlled trials, ziprasidone increased the QTc interval compared to placebo by approximately 10 msec at the highest recommended daily dose of 160 mg.
Based on the above results, the FDA required that Geodon package insert (PI) label warn patients and doctors about prolongation of QTc and risk of sudden death. However, the agency did not require that a severe "black box" warning be placed on the label, a safeguard the agency reserves for drugs deemed to have especially worrisome side effects. Pfizer was able to convince the FDA that patients are not required to undergo ECG prior to and during the maintenance treatment with Geodon.
The following is a patient summary information about Geodon:
WHO SHOULD NOT TAKE GEODON?
Anything that can increase the chance of a heart rhythm abnormality should be avoided. Therefore, do not take GEODON if:
1. You have certain heart diseases, for example, long QT syndrome (acquired or born with), a recent heart attack, severe heart failure, or certain irregularities of heart rhythm (discuss the specifics with your doctor).
2. You are currently taking medications that should not be taken in combination with Geodon, for example, quinidine (Quinaglute), pimozide (Orap), sotalol (Betapace, Sotacor), thioridazine (Mellaril), sparfloxacin (Zagam), or moxifloxacin.
WHAT TO TELL YOUR DOCTOR BEFORE YOU START GEODON?
Be sure you telll your doctor if:
1. have had any problem with the way your heart beats or any heart related illness or disease
2. any family history of heart disease
3. are taking or have recently taken any prescription medicines
4. are taking any over-the-counter (OTC) medicines you can buy without a prescription, including natural/herbal remedies
5. have had any problems with your liver
6. are pregnant, might be pregnant, or plan to get pregnant
7. are breast feeding
8. are allergic to any medicines
9. have ever had an allergic reaction ziprasidone or any of the other ingredients of Geodon capsules.
HOW TO TAKE GEODON?
1. Take Geodon only as directed by your doctor.
2. Swallow the capsules whole.
3. The capsules should be taken with food. (Increases absorption by 60%. If you have been taking it with food then decide to take it on an empty stomach, the absorption and subsequently blood level of Geodon will decrease. This may lead to relapse of your illness.)
4. It is best to take Geodon at the same time each day. (Recommended dosing interval is twice a day.)
5. Do not change your dose or stop taking your medicine without your doctor's approval.
6. Keep taking your capsules, even when you feel better.
NOTIFY YOUR DOCTOR IMMEDIATELY IF YOU (could mean you're having heart rhythm abnormality):
1. Faint or lose consciousness
2. Feel a change in the way that your heart beats (palpitations)
COMMON SIDE EFFECTS OF GEODON:
1. Feeling unusually tired or sleepy
2. Nausea or upset stomach
3. Constipation
4. Dizziness
5. Restlessness
6. Abnormal muscle movements, including tremor, shuffling, and uncontrolled involuntary movements
7. Diarrhea
8. Rash
9. Increased cough/runny nose
DOSING RECOMMENDATIONS:
1. For acute schizophrenic symptoms: A dose of 80 mg to 160 mg (in 2 divided doses) found to be effective. Initial dose is 20 mg twice a day with food. Dosage adjustments, if indicated, should generally occur at intervals of not less than 2 days, as steady state is achieved within 1 to 3 days.
2. For maintenance treatment in schizophrenia: In a one-year trial of ziprasidone, 40 mg/day dose, which may be too low for acute treatment, appears to be efficacious in maintenance.
3. For depression and anxiety: During Geodon clinical trials with schizophrenic and schizoaffective patients, both 120 mg/day and 160 mg/day (60 mg twice a day and 80 mg twice a day, respectively), doses have been found to significantly improve depression and anxiety symptoms compared to placebo. (Note: Geodon is not approved by the FDA for treatment of depression and anxiety.)
HOW GEODON MIGHT WORK FOR DEPRESSIVE AND ANXIETY DISORDERS?
Geodon is a moderate inhibitor of reuptake of both serotonin and norepinephrine, which is characteristic of many antidepressants, suggesting possible effectiveness in depression and anxiety. Furthermore, Geodon has 5HT1A agonism (like BuSpar), suggesting possible anti-anxiety and antidepressant effects. Although unlikely to be used primarily for anxiety, one double-blind study of predental anxiety compared a single oral dose of Geodon 20 mg to diazepam (Valium) 10 mg in 90 patients. The study found both drugs to be effective in reducing anxiety prior to dental surgery, with Geodon producing less sedatiion. This suggests that Geodon does have anti-anxiety effects which are not due to sedation.
PHARMACOLOGY OF GEODON:
Geodon is a highly potent antagonist of 5HT2A receptors and a less potent antagonist of D2 receptors, with a binding affinity ratio of 5HT2A/D2 which may be higher than any antipsychotic either currently in use or in late stage of development. Geodon is also a potent antagonist of 5HT2C and 5HT1D receptors as well as potent agonist of 5HT1A receptors. It has modest affinity for H1 (Histamine 1) receptors with almost no affinity for M1 (muscarinic, cholinergic) receptors. Its modest affinity for H1 and alpha1 receptors suggests a low risk of sedation and hypotension (drop in blood pressure). Its low affinity for M1 cholinergic receptors suggests a low risk for cognitive side effects.
Geodon is mainly metabolized by the liver enzyme CYP3A4. Theoretically, drugs that inhibit the action of this enzyme such as Erythromycin, nefazodone (Serzone), ketoconazole (Nizoral), cimetidine (Tagamet), some protease inhibitors (drugs for HIV) and grapefruit juice may raise the blood level of Geodon. On the other hand, drugs that induce the action of this enzyme such as carbamazepine (Tegretol), phenytoin (Dilantin), phenobarbital, rifampin (Rifadin), and some protease inhbitors may decrease the blood level of Geodon.
GEODON AND WEIGHT GAIN:
Analysis of data of antipsychotics and weight gain found that among atypical antipsychotics Geodon has the least potential to cause weight gain. The estimated weight gain after 10 weeks of treatment is 0.04 kg for Geodon as compared to 4.45 kg for Clozaril, 4.15 kg for Zyprexa, and 2.10 kg for Risperdal.
GEODON MAY BE EFFECTIVE IN TOURETTE'S DISORDER:
One double-blind placebo-controlled pilot study of Geodon in patients with Tourette's disorder aged 7-17 years found that Geodon (16 patients) in flexible doses of 10-40 mg/day was superior to placebo (12 patients) in reducing the severity and number of tics.
FWIW, originally ziprasidone was to named commercially as Zeldox. But the FDA asked Pfizer to choose a different name to avoid being mistaken for other drugs with sound-alike names, e.g., Zyvox, an antibiotic.
++++++++++++++++++++++++++++++
> To all those in waiting,
> My pDoc just phoned to say he has some "zip" samples awaiting me. It's finally here!
>
> Blessings,
>
> Chris A.
poster:Sunnely
thread:54700
URL: http://www.dr-bob.org/babble/20010302/msgs/55961.html