Remoxipride- Antipsychotic agent- Invetigational drug
Drug Name:Remoxipride- Antipsychotic agent- Invetigational drug
List Of Brands:
Indication Type Description:
Indication
Adverse Reaction
Pharmacology/ Pharmacokinetics
Indication:
Schizophrenia
Summary-
Available data suggests that remoxipride is a safe and effective treatment for schizophrenia.
Its favourable side effect profile makes it an important therapeutic option for patients unable
to tolerate traditional antispsychotic agents. Additional comparative studies are necessary
to clarify its overal role in the treatment of schizophrenia and evaluate its potential to cause
tardive dyskenia
An NDA for remoxipride was filed in December 1988. currently it is phase III clinical trials
for the treatment of acute and chronic schizophrenia. because of recent reports of aplastic
anemia, including one death , in European patients, Astra-Merck notified investigators to
discontinue the drug.
The company has recommended restricting the use of this drug to patients who have failed
other antipsychotics.
The drug which will be marketed as Roxiam by Astra/Merck, is currently available in
Luxumbourg. The NDA was withdrawn in December 1993.
Adverse Reaction:
Side effects-
Remoxipride, like other atypical antipsychotic agents eg. clozapine,(Clozaril) causes less
frequently extrapyramidal symptoms(EPS) than the classic antipychotic agents,
eg Haloperidol . Long term comparative trials reported an EPS incidence of 2% to 15%
and 7% to 27% in the remoxipride and haloperidol treated groups respy.
Pooled data from nine comparative trials with haloperidol also showed a lower incidence
of insomnia tiredness/drowsiness, difficulty in concentrations and dry mouth in the remoxipride treated group.
Although isolated reports of cardiovascular effects such as postural hypotension are
documented , they are not considered to be clinically significant
Pharmacology/ Pharmacokinetics:
Pharmacology-
Remoxipride a substituted benzamide, is an atypical antipsychotic agent. It is weak,
but selective , dopamide-2(D2) receptor antagonist. D2 receptors are thought to act in
a inhibitory manner on adenylate cyclase, while dopamine-1(D1) receptors are
associated with adenylate cyclase stimulation.
Remoxipride has a marked affinity for sigma receptors which mediate with opiate effects.
Clinical significance is unknown. There is a wide range between the dose that produces
catalapsy, suggesting a favorable separation between the dose associated with
antipsychotic effect and that producing extrapyrimal symptoms.
Administration of remoxipride causes a significant transcient increase in prolactin release,
however, prolonged admin (> 15days) results in a reduction in this response.
Pharmacokinetics-
Remoxipride is almost completely absorbed after oral administration with a bioavailability
of 96% for both standard and controlled release(CR formulation), there is no first pass
metabolism. Plasma levels peak within 1 to 2 hours after admin of standard formulations
and within 2 to 6 hours after CR formulations and are linearly related to dose.
Volume of distribution averages 0.5 to 0.7L/kg. Protein binding averages 80% , CSF levels
average 6% to 17% of total plasma levels. Breast milk concentrations are app 30% of those in plasma
Aapproximetely 70% of the administered dose is metabolised in the liver to six inactive
oxidised metabolites. Plasma concentration of unchanged metablites are higher in slow
debirisoquine metabolizers. Betweeen 10% and 40% of an oral dose is excreted
unchanged in the urine. Plasma eliimination half-life averages 4 to 7 hours.
Clinical trials-
Remoxiprride is an effective treatment for chronic schizophrenia and acute exacerbations
of chronic schizophrenia. Improvemetnt was documented in both positive (eg. thought
disturbances, hostility /suspciousness, hallucinations, delusions) and negative
(eg. emotional withdrawal , motor retardation) symptoms.
In doses of 150mg to 600mg/day , remoxipiride had similar antipsychotic efficacy to
haloperidol (eg Haldol 5 to 45mg/day and thioridazine (eg.Mellaril 150 to 750mg/day)
In most clinical trails therapy was initiated with 300mg/day .Patients responded to total
daily doses of 300 to 450mg/day (maximum doses 600mg/day), during initiation of
therapy, and were tapered to usual maintenance doses of 150 to 300mg/day.
Dosages adjustment were made to more frequency than every 3 days and were based on
patient response.
Repoxipride may also be effective against treatment acute mania
