levosulpiride
levosulpiride is the levo isomer of sulpiride although the properties are the same.
Adverse Effects, Treatment, and Precautions
As for Chlorpromazine.
Sleep disturbances, overstimulation, and agitation may occur. Extrapyramidal effects appear to be as frequent as with chlorpromazine but have usually been mild. It has been suggested that sulpiride is less likely to cause tardive dyskinesia but good evidence of any important difference is lacking. Sulpiride is less likely to cause sedation than chlorpromazine and antimuscarinic effects are minimal. Cardiovascular effects such as hypotension are generally rare although they may occur with overdosage.
Sulpiride should be given with care to manic or hypomanic patients in whom it may exacerbate symptoms.
Breast feeding.
Sulpiride may be distributed into breast milk and the BNF recommends that its use should be avoided in mothers wishing to breast feed.
On the fifth day after starting D-sulpiride, DL-sulpiride, or L-sulpiride in a dose of 50 mg twice daily, mean concentrations of sulpiride in breast milk from 45 women were 840, 850, and 810 nanograms/mL respectively.
Effects on the cardiovascular system.
Sulpiride 100 mg by mouth caused an attack of hypertension in 6 of 26 hypertensive patients; in 4 it induced a rise in urinary excretion of vanillylmandelic acid and catecholamines. A transient rise in blood pressure and catecholamines after sulpiride occurred in 3 patients who were found to have a phaeochromocytoma; another patient probably had a phaeochromocytoma. The means by which sulpiride provoked hypertension were not known but appeared to be due to a noradrenergic effect. Sulpiride should be avoided during the treatment of phaeochromocytoma, and prescribed with great care in hypertensive patients.
Porphyria.
Sulpiride is considered to be unsafe in patients with porphyria because it has been shown to be porphyrinogenic in animals.
Renal impairment.
For the precautions to be observed in patients with impaired renal function, see under Uses and Administration.
Interactions
As for Chlorpromazine
Gastrointestinal drugs.
Giving sulpiride with therapeutic doses of sucralfate or an antacid containing aluminium and magnesium hydroxides to 6 healthy subjects reduced the mean oral bioavailability of sulpiride by 40 and 32%, respectively. When sulpiride was given 2 hours after the antacid or sucralfate (each in 2 subjects), bioavailability was reduced by about 25%. This interaction was expected to be clinically significant, and it was recommended that sulpiride should be given before, rather than with or after, sucralfate or antacids.
Pharmacokinetics
Sulpiride is slowly absorbed from the gastrointestinal tract; peak plasma concentrations are attained 3 to 6 hours after ingestion. Bioavailability is low and subject to interindividual variation. It is rapidly distributed to the tissues but passage across the blood-brain barrier is poor. Sulpiride is about 40% bound to plasma proteins and is reported to have a plasma half-life of about 8 to 9 hours. It is excreted in the urine and faeces, mainly as unchanged drug. Sulpiride is distributed into breast milk.
Uses and Administration
Sulpiride is a substituted benzamide antipsychotic that is reported to be a selective antagonist of central dopamine (D2, D3, and D4) receptors. It is also claimed to have mood elevating properties.
Sulpiride is mainly used in the treatment of psychoses such as schizophrenia. It has also been given in the management of Tourette's syndrome, anxiety disorders, depression, vertigo, and benign peptic ulceration. Levosulpiride, the L-isomer of sulpiride, has been used similarly to sulpiride.
In the treatment of schizophrenia initial doses of 200 to 400 mg of sulpiride are given twice daily by mouth, increased if necessary up to a maximum of 1.2 g twice daily in patients with mainly positive symptoms or up to a total of 800 mg daily in patients with mainly negative symptoms. Patients with mixed positive and negative symptoms, with neither predominating, are given usual doses of 400 to 600 mg twice daily. Lower initial doses have been recommended in elderly patients, subsequently adjusted as required. A daily dose of 3 to 5 mg/kg may be given by mouth to children over 14 years of age.
Sulpiride is also given in some countries by intramuscular injection, in usual doses ranging from 200 to 800 mg daily.
Dosage adjustment is advised in patients with renal impairment.
Administration in renal impairment.
A single intravenous dose of sulpiride 100 mg was given to 6 healthy subjects with normal renal function (creatinine clearance greater than 90 mL/minute) and to 3 groups of 6 patients each with creatinine clearances (CC) in the ranges of 30 to 60, 10 to 30, and less than 10 mL/minute. There was a progressive diminution in the rate of elimination and an increase in half-life with decreasing renal function. The mean plasma elimination half-lives were 5.90, 11.02, 19.27, and 25.96 hours in the 4 groups, respectively.
In the UK it has been recommended that the dose be reduced according to CC as follows:
CC 30 to 60 mL/minute: two-thirds standard dose, or prolong dosage interval by a factor of 1.5
CC 10 to 30 mL/minute: half standard dose, or double dosage interval
CC less than 10 mL/minute: one-third standard dose, or triple dosage interval
However, the BNF suggests that sulpiride should be avoided if possible in moderate renal impairment.
Chorea.
Antipsychotics have some action against choreiform movements as well as being of use to control the behavioural disturbances of Huntington's chorea. Although sulpiride was found to have produced an overall reduction in abnormal movements in 11 patients with Huntington's chorea when compared with placebo in a double-blind study there was generally no accompanying functional improvement and patients with mild disease tended to worsen when taking sulpiride.
Gastrointestinal disorders.
Although sulpiride is used in some countries as an adjunct in the treatment of peptic ulcer disease it is not among the more usual drugs used for this indication. Efficacy has also been claimed for sulpiride or levosulpiride in a variety of other gastrointestinal disorders, including irritable bowel disease, gastrointestinal motility disorders, and nausea and vomiting, but again they are not among the drugs usually considered for use in these conditions.
Lactation.
Drug therapy has been used occasionally to stimulate lactation in breast-feeding mothers, although mechanical stimulation of the nipple remains the primary method. Dopamine antagonists such as sulpiride can produce modest increases in breast milk production although metoclopramide has been more widely used. However, there is concern about the adverse effects of these drugs. As sulpiride appears in breast milk and may be associated with adverse effects in the infant it has been recommended that it should not be used to enhance milk production.
Schizophrenia.
A systematic review of the use of sulpiride for schizophrenia or serious mental illness concluded that while sulpiride might be as effective as the classical antipsychotics for schizophrenia and appeared to produce few adverse effects, evidence of its value for treating negative symptoms was lacking. Comparisons with the atypical antipsychotic drugs were also lacking.
Tourette's syndrome.
When drug treatment is needed for tics and behavioural disturbances in Tourette's syndrome dopamine antagonists such as the antipsychotics haloperidol or pimozide are most commonly used but sulpiride has also been tried. Although unlicensed in the UK for the treatment of Tourette's syndrome, the BNFC has suggested that oral doses of sulpiride 200 to 400 mg twice daily may be given to adolescents aged from 14 to 18 years.