Source: Υπουργείο Υγείας (CY) Revision Year: 2017 Publisher: MEDOCHEMIE LTD, 1-10 Constantinoupoleos street, 3011 Limassol, Cyprus
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Nautisol should be avoided in patients with liver or renal dysfunction, Parkinson’s disease, hypothyroidism, cardiac failure, phaeochromocytoma, myasthenia gravis, prostate hypertrophy. It should be avoided in patients known to be hypersensitive to phenothiazines or with a history of narrow angle glaucoma or agranulocytosis.
Close monitoring is required in patients with epilepsy or a history of seizures, as phenothiazines may lower the seizure threshold.
As agranulocytosis has been reported, regular monitoring of the complete blood count is recommended. The occurrence of unexplained infections or fever may be evidence of blood dyscrasia (see section 4.8), and requires immediate haematological investigation.
It is imperative that treatment be discontinued in the event of unexplained fever, as this may be a sign of neuroleptic malignant syndrome (pallor, hyperthermia, autonomic dysfunction, altered consciousness, muscle rigidity). Signs of autonomic dysfunction, such as sweating and arterial instability, may precede the onset of hyperthermia and serve as early warning signs. Although neuroleptic malignant syndrome may be idiosyncratic in origin, dehydration and organic brain disease are predisposing factors.
Acute withdrawal symptoms, including nausea, vomiting and insomnia, have very rarely been reported following the abrupt cessation of high doses of neuroleptics. Relapse may also occur, and the emergence of extrapyramidal reactions has been reported. Therefore, gradual withdrawal is advisable.
In schizophrenia, the response to neuroleptic treatment may be delayed. If treatment is withdrawn, the recurrence of symptoms may not become apparent for some time.
Neuroleptic phenothiazines may potentiate QT interval prolongation which increases the risk of onset of serious ventricular arrhythmias of the torsade de pointes type, which is potentially fatal (sudden death). QT prolongation is exacerbated, in particular, in the presence of bradycardia, hypokalaemia, and congenital or acquired (i.e. drug induced) QT prolongation. The risk-benefit should be fully assessed before Nautisol treatment is commenced. If the clinical situation permits, medical and laboratory evaluations (e.g. biochemical status and ECG) should be performed to rule out possible risk factors (e.g. cardiac disease; family history of QT prolongation; metabolic abnormalities such as hypokalaemia, hypocalcaemia or hypomagnesaemia; starvation; alcohol abuse; concomitant therapy with other drugs known to prolong the QT interval) before initiating treatment with Nautisol and during the initial phase of treatment, or as deemed necessary during the treatment (see also sections 4.5 and 4.8).
Avoid concomitant treatment with other neuroleptics (see section 4.5).
In randomised clinical trials versus placebo performed in a population of elderly patients with dementia and treated with certain atypical antipsychotic drugs, a 3-fold increase of the risk of cerebrovascular events has been observed. The mechanism of such risk increase is not known. An increase in the risk with other antipsychotic drugs or other populations of patients cannot be excluded. Nautisol should be used with caution in patients with stroke risk factors.
As with all antipsychotic drugs, Nautisol should not be used alone where depression is predominant. However, it may be combined with antidepressant therapy to treat those conditions in which depression and psychosis coexist.
Because of the risk of photosensitisation, patients should be advised to avoid exposure to direct sunlight.
To prevent skin sensitisation in those frequently handling preparations of phenothiazines, the greatest care must be taken to avoid contact of the drug with the skin (see section 4.8).
It should be used with caution in the elderly, particularly during very hot or very cold weather (risk of hyper-, hypothermia).
The elderly are particularly susceptible to postural hypotension.
Nautisol should be used cautiously in the elderly owing to their susceptibility to drugs acting on the central nervous system and a lower initial dosage is recommended. There is an increased risk of drug-induced Parkinsonism in the elderly particularly after prolonged use. Care should also be taken not to confuse the adverse effects of Nautisol, e.g. orthostatic hypotension, with the effects due to the underlying disorder.
Children: Prochlorperazine has been associated with dystonic reactions particularly after a cumulative dosage of 0.5 mg/kg. It should therefore be used cautiously in children.
Data from two large observational studies showed that elderly people with dementia who are treated with antipsychotics are at a small increased risk of death compared with those who are not treated. There are insufficient data to give a firm estimate of the precise magnitude of the risk and the cause of the increased risk is not known.
Prochlorperazine is not licensed for the treatment of dementia-related behavioural disturbances.
Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since patients treated with antipsychotics often present with acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with Nautisol and preventative measures undertaken.
Hyperglycaemia or intolerance to glucose has been reported in patients treated with antipsychotic phenothiazines. Patients with an established diagnosis of diabetes mellitus or with risk factors for the development of diabetes who are started on Nautisol, should get appropriate glycaemic monitoring during treatment (see section 4.8).
Nautisol contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Adrenaline must not be used in patients overdosed with prochlorperazine.(see section 4.9).
The CNS depressant actions of neuroleptic agents may be intensified (additively) by alcohol, barbiturates and other sedatives. Respiratory depression may occur.
Anticholinergic agents may reduce the antipsychotic effect of neuroleptics and the mild anticholinergic effect of neuroleptics may be enhanced by other anticholinergic drugs, possibly leading to constipation, heat stroke, etc.
Some drugs interfere with absorption of neuroleptic agents: antacids, anti-Parkinson drugs and lithium.
Where treatment for neuroleptic-induced extrapyramidal symptoms is required, anticholinergic antiparkinsonian agents should be used in preference to levodopa, since neuroleptics antagonise the antiparkinsonian action of dopaminergics.
High doses of neuroleptics reduce the response to hypoglycaemic agents, the dosage of which might have to be raised.
The hypotensive effect of most antihypertensive drugs especially alpha adrenoceptor blocking agents may be exaggerated by neuroleptics.
The action of some drugs may be opposed by phenothiazine neuroleptics; these include amfetamine, levodopa, clonidine, guanethidine, adrenaline.
Increases or decreases in the plasma concentrations of a number of drugs, e.g. propranolol, phenobarbital have been observed but were not of clinical significance.
Simultaneous administration of desferrioxamine and prochlorperazine has been observed to induce transient metabolic encephalopathy characterised by loss of consciousness for 48-72 hours.
There is an increased risk of arrhythmias when neuroleptics are used with concomitant QT prolonging drugs (including certain antiarrhythmics, antidepressants and other antipsychotics) and drugs causing electrolyte imbalance.
There is an increased risk of agranulocytosis when neuroleptics are used concurrently with drugs with myelosuppressive potential, such as carbamazepine or certain antibiotics and cytotoxics.
In patients treated concurrently with neuroleptics and lithium, there have been rare reports of neurotoxicity.
There is inadequate evidence of safety in pregnancy. There is evidence of harmful effects in animals. Prochlorperazine should be avoided in pregnancy unless the physician considers it essential. Neuroleptics may occasionally prolong labour and at such time should be withheld until the cervix is dilated 3-4 cm. Possible adverse effects on the neonate include lethargy or paradoxical hyperexcitability, tremor and low apgar score.
Neonates exposed to antipsychotics (including prochlorperazine) during the third trimester of pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that may vary in severity and duration following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, bradycardia, tachycardia, feeding disorder, meconium ileus, delayed meconium passage, abdominal bloating. Consequently, newborns should be monitored carefully in order to plan appropriate treatment.
Phenothiazines may be excreted in milk, therefore breast feeding should be suspended during treatment.
Patients should be warned about drowsiness during the early days of treatment and advised not to drive or operate machinery.
Generally, adverse reactions occur at a low frequency; the most common reported adverse reactions are nervous system disorders.
Adverse reactions are listed below, by system organ class and by frequency. Frequencies are defined as: Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from available data).
A mild leukopenia occurs in up to 30% of patients on prolonged high dosage.
Rare: Agranulocytosis may occur rarely: it is not dose related (see section 4.4, above).
Not known: Hyperprolactinaemia which may result in galactorrhoea, gynaecomastia, amenorrhoea; impotence.
Not known: Hyponatraemia, syndrome of inappropriate antidiuretic hormone secretion.
Common:
Not known: Ocular changes and the development of metallic greyish-mauve coloration of exposed skin have been noted in some individuals mainly females, who have received chlorpromazine continuously for long periods (four to eight years). This could possibly happen with prochlorperazine.
Not known: ECG changes include QT prolongation (as with other neuroleptics), ST depression, U-Wave and T-Wave changes. Cardiac arrhythmias, including ventricular arrhythmias and atrial arrhythmias, a-v block, ventricular tachycardia, which may result in ventricular fibrillation or cardiac arrest have been reported during neuroleptic phenothiazine therapy, possibly related to dosage. Pre-existing cardiac disease, old age, hypokalaemia and concurrent tricyclic antidepressants may predispose.
There have been isolated reports of sudden death, with possible causes of cardiac origin (see section 4.4, above), as well as cases of unexplained sudden death, in patients receiving neuroleptic phenothiazines.
Common: hypotension, usually postural, commonly occurs. Elderly or volume depleted subjects are particularly susceptible; it is more likely to occur after intramuscular injection.
Not known: Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein thrombosis have been reported with antipsychotic drugs.
Not known: dry mouth may occur.
Not known: Respiratory depression is possible in susceptible patients. Nasal stuffiness may occur.
Not known: Jaundice, usually transient, occurs in a very small percentage of patients taking neuroleptics. A premonitory sign may be sudden onset of fever after one to three weeks of treatment followed by the development of jaundice. Neuroleptic jaundice has the biochemical and other characteristics of obstructive jaundice and is associated with obstruction of the canaliculi by bile thrombi; the frequent presence of an accompanying eosinphilia indicates the allergic nature of this phenomenon. Treatment should be withheld on the development of jaundice (see section 4.4).
Rare: Contact skin sensitisation may occur rarely in those frequently handling preparations of certain phenothiazines (see section 4.4). Skin rashes of various kinds may also be seen in patients treated with the drug. Patients on high dosage should be warned that they may develop photosensitivity in sunny weather and should avoid exposure to direct sunlight.
Not known: Drug withdrawal syndrome neonatal (see section 4.6).
Not known: Neuroleptic malignant syndrome (hyperthermia, rigidity, autonomic dysfunction and altered consciousness) may occur with any neuroleptic (see section 4.4, above).
Reporting suspected adverse reactions is an important way to gather more information to continuously monitor the benefit/risk balance of the medicinal product. Any suspected adverse reactions should be reported to Pharmaceutical Services, Ministry of Health, CY-1475, www.moh.gov.cy/phs, Fax: +357 22608649.
None known.
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