Motivom 10 Odt 10 mg tablet

MOTIVOM 10 ODT is indicated in adults and children over 35 kg for:

• Short-term management of delayed gastric emptying of functional origin with gastroesophageal reflux and/or dyspepsia.
• Control of nausea and vomiting of central or local origin.
• As an anti-emetic in patients receiving cytostatic and radiation therapy.
• Facilitation of radiological examination of the upper gastrointestinal tract.

Posology

Adults and adolescents u2265 12 years of age and weighing u2265 35 kg, and children weighing u2265 35 kg

The dose of MOTIVOM 10 ODT should be the lowest effective dose for the individual situation (typically 30 mg/day) with a maximum daily oral dose of 40 mg. Usually, the maximum treatment duration should not exceed one week for the treatment of acute nausea and vomiting. If nausea and vomiting persist for longer than one week, patients should consult their doctors. For other indications, the initial duration of treatment is up to four weeks. If treatment exceeds four weeks, patients should be re-evaluated and the need for continued treatment reassessed.

Formulation (domperidone per unit)

Dosage Maximum dose per day

Orodispersible tablet (10 mg per tablet) 1 tablet three to four times per day 40 mg (4 x 10 mg tablet)

Special populations

Renal impairment

Since the elimination hatf-life of domperidone is prolonged in severe renal impairment (serum creatinine > 6 mg/100 mL, i.e.> 0,6 mmol/L), the dosing frequency of MOTIVOM 10 ODT should be reduced to once or twice daily, depending on the severity of the impairment, and the dose may need to be reduced. Patients with severe renal impairment should be reviewed regularly.

Hepatic impairment

MOTIVOM 10 ODT is contraindicated for patients with moderate (Child-Pugh 7 to 9) or severe (Child-Pugh > 9) hepatic impairment (see section 4.3). Dose adjustment is not required for patients with mild (Child-Pugh 5 to 6) hepatic impairment (see section 5.2).

Paediatric population

Tablets are unsuitable for use in children weighing less than 35 kg.

Method of administration

MOTIVOM 10 ODT is for oral administration. The orodispersible tablet dissolves rapidly in the mouth with the help of the saliva, and can be taken with or without water. When taken without water, the MOTIVOM 10 ODT tablet should be placed on the tongue and dissolved in the mouth before swallowing. If convenient, a glass of water can be taken afterwards. It is recommended to take MOTIVOM 10 ODT, 15 u2013 30 minutes before meals. If taken after meals, absorption of the medicine is somewhat delayed.

MOTIVOM 10 ODT is contraindicated in the following situations:

• Known hypersensitivity to domperidone or any of the excipients in MOTIVOM 10 ODT (see section 6.1).
• Prolactin-releasing pituitary tumour (prolactinoma).
• When stimulation of the gastric motility could be harmful e.g., in patients with gastrointestinal haemorrhage, mechanical obstruction or perforation.
• In patients with moderate or severe hepatic impairment (see section 5.2).
• In patients who have known existing prolongation of cardiac conduction intervals, particularly QTc or family history thereof, patients with significant electrolyte disturbances or underlying cardiac diseases, such as congestive heart failure (see section 4.4).
• Hypokalaemia, hypomagnesaemia, hyperkalaemia.
• Bradycardia or heart block.
• Co-administration with medicines known to induce torsades de pointes and/or with QT-prolonging medicines (see sections 4.4 and 4.5).
• Co-administration with potent CYP3A4 inhibitors (regardless of their QT prolonging effects) (see section 4.5).

Cardiovascular effects

Domperidone has been associated with prolongation of the QT interval on the electrocardiogram. During post-marketing surveillance, there have been cases of QT prolongation and torsades de pointes in patients taking domperidone, as in MOTIVOM 10 ODT. These reports included patients with confounding risk factors, electrolyte abnormalities and concomitant treatment which may have been contributing factors (see section 4.3 and 4.8).

Epidemiological studies showed that domperidone was associated with an increased risk of serious ventricular dysrhythmias or sudden cardiac death (see section 4.8). A higher risk was observed in patients older than 60 years of age, patients taking daily doses greater than 30 mg, and patients concurrently taking QT-prolonging medicines or CYP3A4 inhibitors. Therefore, MOTIVOM 10 ODT should be used with caution in older patients.

MOTIVOM 10 ODT should be used at the lowest effective dose in adults and adolescents 12 years of age and older (see section 4.2).

MOTIVOM 10 ODT is contraindicated in patients with known existing prolongation of cardiac conduction intervals, particularly QTc, in patients with significant electrolyte disturbances (hypokalaemia, hyperkalaemia, hypomagnesaemia), or bradycardia, or in patients with underlying cardiac diseases such as congestive heart failure due to increased risk of ventricular dysrhythmia (see section 4.3.). Electrolyte disturbances (hypokalaemia, hyperkalaemia, hypomagnesaemia) or bradycardia are known to be conditions increasing the prodysrhythmic risk.

Treatment with MOTIVOM 10 ODT should be stopped if signs or symptoms occur that may be associated with cardiac dysrhythmia, and the patient should consult their medical practitioner. Patients should be advised to promptly report any cardiac symptoms.

Use with apomorphine

MOTIVOM 10 ODT is contraindicated with QT prolonging medicines, including apomorphine.

Renal impairment

The elimination half-life of domperidone is prolonged in severe renal impairment. For repeated administration, the dosing frequency of MOTIVOM 10 ODT should be reduced to once or twice daily depending on the severity of the impairment. The dose may also need to be reduced.

Children

MOTIVOM 10 ODT is unsuitable for use in children weighing less than 35 kg.

MOTIVOM 10 ODT contains aspartame

Aspartame is a source of phenylalanine. It may be harmful if you have phenylketonuria (PKU), a rare genetic disorder in which phenylalanine builds up because the body cannot remove it properly.

The main metabolic pathway of MOTIVOM 10 ODT is through CYP3A4. In vitro data suggest that the concomitant use of medicines that significantly inhibit this enzyme may result in increased plasma levels of domperidone. Increased risk of occurrence of QT-interval prolongation, due to pharmacodynamic and/or pharmacokinetic interactions.

Concomitant use of the following substances is contraindicated:

• QTc prolonging medicines:
• antidysrhythmics class IA (e.g., disopyramide, hydroquinidine, quinidine)
• antidysrhythmics class III (e.g., amiodarone, dofetilide, dronedarone, ibutilide, sotalol)
• certain antipsychotics (e.g., haloperidol, pimozide, sertindole)
• certain antidepressants (e.g., citalopram, escitalopram)
• certain antibiotics (e.g., erythromycin, levofloxacin, moxifloxacin, spiramycin)
• certain antifungal medicines (e.g., pentamidine)
• certain antimalarial medicines (in particular halofantrine, lumefantrine)
• certain gastrointestinal medicines (e.g., cisapride, dolasetron, prucalopride)
• certain antihistaminics (e.g., mequitazine, mizolastine)
• certain medicines used in cancer (e.g., toremifene, vandetanib, vincamine)
• certain other medicines (e.g., bepridil, diphemanil, methadone) (see section 4.3)
• apomorphine (see section 4.4).

Potent CYP3A4 inhibitors (regardless of their QT prolonging effects), i.e.:

• protease inhibitors
• systemic azole antifungals
• some macrolides (erythromycin, clarithromycin, telithromycin) (see section 4.3).

Concomitant use of the following substances is not recommended:

• Moderate CYP3A4 inhibitors i.e. diltiazem, verapamil and some macrolides (see section 4.3).

Concomitant use of the following substances requires caution in use:

Caution with bradycardia and hypokalaemia-inducing medicines, as well as with the following macrolides involved in QT-interval prolongation: azithromycin and roxithromycin (clarithromycin is contraindicated as it is a potent CYP3A4 inhibitor).

The above list of substances is representative and not exhaustive.

Separate in vivo pharmacokinetic/pharmacodynamic interaction studies with oral ketoconazole or oral erythromycin in healthy subjects confirmed a marked inhibition of domperidone's CYP3A4 mediated first pass metabolism by these medicines. With the combination of oral domperidone 10 mg four times daily and ketoconazole 200 mg twice daily, a mean QTc prolongation of 9,8 msec was seen over the observation period, with changes at individual time points ranging from 1,2 to 17,5 msec. With the combination of domperidone 10 mg four times daily and oral erythromycin 500 mg three times daily, mean QTc over the observation period was prolonged by 9,9 msec, with changes at individual time points ranging from 1,6 to 14,3 msec. Both the C max and AUC (area under the curve) of domperidone at steady state were increased approximately three-fold in each of these interaction studies. In these studies, domperidone monotherapy at 10 mg given orally four times daily resulted in increases in mean QTc of 1,6 msec (ketoconazole study) and 2,5 msec (erythromycin study), while ketoconazole monotherapy (200 mg twice daily) led to increases in QTc of 3,8 and 4,9 msec, respectively, over the observation period.

Antacids and antisecretory medicines

Antacids and antisecretory medicines should not be taken simultaneously with oral formulations of MOTIVOM 10 ODT as they lower the oral bioavailability of domperidone. When used concomitantly, MOTIVOM 10 ODT should be taken before meals and antacids or anti-secretory medicines after meals. Reduced gastric acidity impairs the absorption of domperidone. Oral bioavailability is decreased by prior concomitant administration of cimetidine and sodium bicarbonate.

Anticholinergic medicines

Concomitant administration of anticholinergic medicines (e.g., dextromethorphan, diphenhydramine) may antagonise the anti-dyspeptic effects of MOTIVOM 10 ODT.

Prolactin levels

MOTIVOM 10 ODT interferes with serum prolactin levels and may interfere with other hypoprolactinaemic medicines and with some diagnostic tests.

General

Since MOTIVOM 10 ODT has gastrokinetic effects, it could influence the absorption of concomitant orally administered medicines, particularly those with sustained release or enteric coated formulations. However, in patients already stabilised on digoxin or paracetamol, concomitant administration of domperidone did not influence the blood levels of these medicines.

MOTIVOM 10 ODT may also be given with:

• Neuroleptics, the action of which it does not potentiate.
• Dopaminergic agonists (e.g. bromocriptine) and L-dopa, whose unwanted peripheral effects, such as digestive disorders, nausea and vomiting, it suppresses without counteracting their central properties.

Pregnancy

Safety of use during pregnancy has not been established.

Breastfeeding

Domperidone is excreted in human milk and breastfed infants receive less than 0,1 % of the maternal weight-adjusted dose. Occurrence of adverse effects, in particular cardiac effects cannot be excluded after exposure via breast milk. Breastfeeding is not recommended for mothers who are taking MOTIVOM 10 ODT. Caution should be exercised in case of QTc prolongation risk factor in breastfed infants.

Fertility

No data is available on fertility.

MOTIVOM 10 ODT may cause dizziness or somnolence (see section 4.8). Patients should be advised not to drive or use machinery or engage in other activities requiring mental alertness and coordination until they have established how MOTIVOM 10 ODT affects them.

The safety of domperidone, as in MOTIVOM 10 ODT, was evaluated in clinical trials and in post marketing experience. The clinical trials included patients with dyspepsia, gastroesophageal reflux disorder (GORD), irritable bowel syndrome (IBS), nausea and vomiting or other related conditions. Studies in diabetic gastroparesis or symptoms secondary to chemotherapy or parkinsonism were excluded.

Immune system disorders:

• Less frequent: hypersensitivity

Psychiatric disorders:

• Frequent: depression
• Less frequent: loss of libido, anxiety

Nervous system disorders:

• Frequent: akathisia, somnolence, headache

Gastrointestinal disorders:

• Frequent: dry mouth, diarrhoea

Skin and subcutaneous tissue disorders:

• Frequent: rash, pruritus
• Less frequent: urticaria

Reproductive system and breast disorders:

• Frequent: breast enlargement/gynaecomastia, amenorrhoea, irregular menstruation, lactation disorder, breast tenderness, breast pain, galactorrhoea
• Less frequent: breast discharge, breast swelling

General disorders and administration site conditions:

• Frequent: asthenia

Post-marketing experience:

The following reactions have been reported post-marketing:

Immune system disorders:

• Frequency unknown: anaphylactic reaction (including anaphylactic shock), angioedema

Psychiatric disorders:

• Frequency unknown: agitation, nervousness

Nervous system disorders:

• Frequency unknown: convulsion, extrapyramidal disorder, dizziness

Eye disorders:

• Frequency unknown: oculogyric crisis

Cardiac disorders:

• Frequency unknown: ventricular dysrhythmias (see section 4.4), sudden cardiac death, QTc prolongation, torsade de pointes

Renal and urinary disorders:

• Frequency unknown: urinary retention

Investigations:

• Frequency unknown: abnormal liver function tests, increased blood prolactin

Description of selected adverse events

In clinical studies where domperidone, as in MOTIVOM 10 ODT, was used at higher dosages, for longer duration and for additional indications including diabetic gastroparesis, the frequency of adverse events (apart from dry mouth) was considerably higher. This was particularly evident for pharmacologically predictable events related to increased prolactin. In addition to the reactions listed above, akathisia, breast discharge, breast enlargement, breast swelling, depression, hypersensitivity, lactation disorder, and irregular menstruation were also noted.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of MOTIVOM 10 ODT is important. It allows continued monitoring of the benefit/risk balance of MOTIVOM 10 ODT. Health care providers are requested to report any suspected adverse reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on the SAHPRA website.

Symptoms

Symptoms of over dosage may include agitation, altered consciousness, convulsions, disorientation, somnolence and extrapyramidal reactions.

Treatment

There is no specific antidote to MOTIVOM 10 ODT, but in the event of overdose, standard symptomatic treatment should be given immediately. Administration of activated charcoal, may be useful. Electrocardiogram (ECG) monitoring should be undertaken, because of the possibility of QT interval prolongation. Close medical supervision and supportive therapy is recommended.

Anticholinergic, anti-parkinson medicines may be helpful in controlling the extrapyramidal reactions.