XOMOLIX Solution for injection Ref.[2772] Active ingredients: Droperidol

Central Nervous System

Droperidol may enhance CNS depression produced by other CNS-depressant drugs. Any patient subjected to anaesthesia and receiving potent CNS depressant medicinal products or showing symptoms of CNS depression should be monitored closely.

Concomitant use of metoclopramide and other neuroleptics may lead to an increase in extrapyramidal symptoms and should be avoided (see section 4.5).

Use with caution in patients with epilepsy (or a history of epilepsy) and conditions predisposing to epilepsy or convulsions.

Cardiovascular

Mild to moderate hypotension and occasionally (reflex) tachycardia have been observed following the administration of droperidol. This reaction usually subsides spontaneously. However, should hypotension persist, the possibility of hypovolaemia should be considered and appropriate fluid replacement administered.

Patients with, or suspected of having, the following risk factors for cardiac arrhythmia should be carefully evaluated prior to administration of droperidol:

• a history of significant cardiac disease including serious ventricular arrhythmia, second or third degree atrio-ventricular block, sinus node dysfunction, congestive heart failure, ischemic heart disease and left ventricular hypertrophy;
• family history of sudden death;
• renal failure (particularly when on chronic dialysis);
• significant chronic obstructive pulmonary disease and respiratory failure;
• risk factors for electrolyte disturbances, as seen in patients taking laxatives, glucocorticoids, potassium-wasting diuretics, in association with the administration of insulin in acute settings, or in patients with prolonged vomiting and/or diarrhoea.

Patients at risk for cardiac arrhythmia should have serum electrolytes and creatinine levels assessed and the presence of QT prolongation excluded prior to administration of droperidol.

Continuous pulse oximetry should be performed in patients with identified or suspected risk of ventricular arrhythmia and should continue for 30 minutes following single i.v. administration.

General

To prevent QT prolongation, caution is necessary when patients are taking medicinal products likely to induce electrolyte imbalance (hypokalaemia and/or hypomagnesaemia) e.g. potassium-wasting diuretics, laxatives and glucocorticoids.

Substances inhibiting the activity of cytochrome P450 iso-enzymes (CYP) CYP1A2, CYP3A4 or both could decrease the rate at which droperidol is metabolised and prolong its pharmacological action. Hence, caution is advised if droperidol is given concomitantly with strong CYP1A2 and CYP3A4 inhibitors (see section 4.5).

Patients who have, or are suspected of having, a history of alcohol abuse or recent high intakes, should be thoroughly assessed before droperidol is administered.

In case of unexplained hyperthermia, it is essential to discontinue treatment, since this sign may be one of the elements of malignant syndrome reported with neuroleptics.

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 Xomolix and preventive measures undertaken.

The dose should be reduced in the elderly and those with impaired renal and hepatic function (see section 4.2).

This medicinal product contains less than 1 mmol sodium (23 mg) per 1 ml, i.e. essentially ‘sodium-free’.

Contraindicated for concomitant use

Medicinal products known to cause torsades de pointes through QT prolongation should not be concomitantly administered with droperidol.

Examples include:

• Class IA antiarrhythmics
• Class III antiarrhythmics
• macrolide antibiotics
• fluoroquinolone antibiotics
• antihistamines
• certain antipsychotic medications
• anti-malaria agents
• cisapride, domperidone, methadone, pentamidine.

Concomitant use of medicinal products that induce extrapyramidal symptoms, e.g. metoclopramide and other neuroleptics, may lead to an increased incidence of these symptoms and should therefore be avoided.

Consumption of alcoholic beverages and medicines should be avoided.

Caution is advised for concomitant use

To reduce the risk of QT prolongation, caution is necessary when patients are taking medicinal products likely to induce electrolyte imbalance (hypokalaemia and/or hypomagnesaemia) e.g. potassium-wasting diuretics, laxatives and glucocorticoids.

Droperidol may potentiate the action of sedatives (barbiturates, benzodiazepines, morphine derivatives). The same applies to antihypertensive agents, so that orthostatic hypotension may ensue.

Like other sedatives, droperidol may potentiate respiratory depression caused by opioids.

Since droperidol blocks dopamine receptors, it may inhibit the action of dopamine agonists, such as bromocriptine, lisuride, and of L-dopa.

Substances inhibiting the activity of cytochrome P450 iso-enzymes (CYP) CYP1A2, CYP3A4 or both could decrease the rate at which droperidol is metabolised and prolong its pharmacological action. Hence, caution is advised if droperidol is given concomitantly with CYP1A2 inhibitors, CYP3A4 inhibitors or both.

Pregnancy

A limited amount of clinical data have shown no increase of malformative risk.

Droperidol has not been shown to be teratogenic in rats. Animal studies are insufficient with respect to the effects on pregnancy and embryonal/foetal, parturition and postnatal development.

In newborn babies from mothers under long-term treatment and high doses of neuroleptics, temporary neurological disturbances of extrapyramidal nature have been described.

In practice, as a precautionary measure, it is preferable not to administer droperidol during pregnancy. In late pregnancy, if its administration is necessary, monitoring of the newborn’s neurological functions is recommended.

Breast-feeding

Neuroleptics of the butyrophenone type are known to be excreted in breast milk; treatment with droperidol should be limited to a single administration. Repeat administration is not recommended.

Fertility

There were no effects on fertility in studies conducted in male and female rats (see section 5.3). The clinical effect of droperidol on fertility has not been established.

Droperidol has major influence on the ability to drive and use machines.

Patients should not drive or operate a machine for 24 hours after droperidol administration.

The most frequently reported events during clinical experience are incidents of drowsiness and sedation. In addition, less frequent reports of hypotension, cardiac arrhythmias, neuroleptic malignant syndrome (NMS) and symptoms associated with NMS, plus movement disorders, such as dyskinesias, plus incidents of anxiety or agitation have occurred.

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
Not known (cannot be estimated from the available data)

Blood and lymphatic systems disorders

Very Rare: Blood dyscrasias

Immune system disorders

Rare: Anaphylactic reaction; Angioneurotic oedema; Hyper-sensitivity

Metabolism and nutrition disorders

Not known: Inappropriate anti-diuretic hormone secretion

Psychiatric disorders

Uncommon: Anxiety; Restlessness/Akathisia;

Rare: Confusional states; Agitation

Very Rare: Dysphoria

Not known: Hallucinations

Nervous system disorders

Common: Drowsiness

Uncommon: Dystonia; Oculogyration

Very Rare: Extra-pyramidal disorder; Convulsions; Tremor

Not known: Epileptic fits; Parkinson’s disease;

Cardiac disorders

Uncommon: Tachycardia; Dizziness

Rare: Cardiac arrhythmias, including ventricular arrhythmias

Very Rare: Cardiac arrest; Torsades de pointes; Electrogram QT prolonged

Vascular disorders

Common: Hypotension

Not known: Syncope

Respiratory, thoracic and mediastinal disorders

Not known: Bronchospasm; Laryngospasm

Skin and subcutaneous system disorders

Rare: Rash

General disorders and administration site conditions

Rare: Neuroleptic malignant syndrome (NMS)

Very Rare: Sudden death

Symptoms potentially associated with NMS have occasionally been reported i.e. changes in body temperature, stiffness and fever. An alteration in mental status with confusion or agitation and altered consciousness, have been seen. Autonomic instability may manifest as tachycardia, fluctuating blood pressure, excessive sweating/salivation and tremor. In extreme cases NMS may lead to coma, or renal and/or hepato-biliary problems.

Isolated cases of amenorrhoea, galactorrhoea, gynaecomastia, hyperprolactinaemia, oligomenorrhoea and neonatal drug withdrawal syndrome have been associated with prolonged exposure in psychiatric indications.

Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein thrombosis have been reported with antipsychotic medicinal products-frequency unknown.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme, www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Incompatible with barbiturates. This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.