4.1. Therapeutic indications

Hyperprolactinaemia (idiopathic or originating from a prolactin-secreting pituitary microadenoma or macroadenoma).

4.2. Posology and method of administration

Since dopaminergic stimulation may lead to symptoms of orthostatic hypotension, the dosage of NORPROLAC should be initiated gradually with the aid of the 'starter pack', and given only at bedtime.

Adults

The optimal dose must be titrated individually on the basis of the prolactin- lowering effect and tolerability.

With the 'starter pack' treatment begins with 25 micrograms/day for the first 3 days, followed by 50 micrograms/day for a further 3 days. From day 7 onwards, the recommended dose is 75 micrograms/day.

If necessary, the daily dose may then be increased stepwise until the optimal individual response is attained. The usual maintenance dosage is 75 to 150 micrograms/day.

Daily doses of 300 micrograms or higher doses are required in less than one- third of the patients.

In such cases, the daily dosage may be increased in steps of 75 to 150 micrograms at intervals not shorter than 4 weeks until satisfactory therapeutic effectiveness is achieved or reduced tolerability, requiring the discontinuation of treatment, occurs.

Elderly

Experience with the use of NORPROLAC in elderly patients is not available.

Children

Experience with the use of NORPROLAC in children is not available.

Method of Administration

NORPROLAC should be taken once a day with some food at bedtime.

4.3. Contraindications

Hypersensitivity to the drug.

Impaired hepatic or renal function

For procedure during pregnancy, (see section 4.6 Pregnancy and lactation).

4.4. Special warnings and precautions for use

Fertility may be restored by treatment with NORPROLAC. Women of child-bearing age who do not wish to conceive should therefore be advised to practice a reliable method of contraception.

Since orthostatic hypotension may result in syncope, it is recommended to check blood pressure both lying and standing during the first days of therapy and following dosage increases.

In a few cases, including patients with no previous history of mental illness, treatment with NORPROLAC has been associated with the occurrence of acute psychosis, usually reversible upon discontinuation. Particular caution is required in patients who have had psychotic episodes in their previous history.

To date no data is available with the use of NORPROLAC in patients with impaired renal or hepatic function (see Section 4.3 Contraindications).

NORPROLAC has been associated with somnolence. Other dopamine agonists can be associated with sudden sleep onset episodes, particularly in patients with Parkinson's disease. Patients must be informed of this and advised to exercise caution whilst driving or operating machines during treatment with NORPROLAC.

Patients who have experienced somnolence must not drive or operate machines. Furthermore, a reduction of dosage or termination of therapy may be considered (see Section 4.7 Effects on the ability to drive and use machines).

Impulse control disorders

Patients should be regularly monitored for the development of impulse control disorders. Patients and carers should be made aware that behavioural symptoms of impulse control disorders including pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists including NORPROLAC. Dose reduction/tapered discontinuation should be considered if such symptoms develop.

Dopamine agonist withdrawal syndrome (DAWS) has been reported following discontinuation of dopamine agonists. Non-motor adverse effects may occur when discontinuing dopamine agonist. Symptoms which have been reported with other dopamine agonists include apathy, anxiety, depression, fatigue, sweating and pain which may be severe. When treatment with quinagolide is stopped there is a possible risk that DAWS may occur in some patients. Patients could therefore benefit from tapering of the quinagolide dose.

NORPROLAC should be kept out of the reach and sight of children.

4.5. Interaction with other medicinal products and other forms of interaction

No interactions between NORPROLAC and other drugs have so far been reported. On theoretical grounds, a reduction of the prolactin-lowering effect could be expected when drugs (e.g. neuroleptic agents) with strong dopamine antagonistic properties are used concomitantly. As the potency of NORPROLAC for 5-HT1 and 5-HT2 receptors is some 100 times lower than that for D2 receptors, an interaction between NORPROLAC and 5-HT1a receptors is unlikely. However, care should be taken when using these medicaments concomitantly.

The tolerability of NORPROLAC may be reduced by alcohol.

4.6. Pregnancy and lactation

Pregnancy

Animal data provide no evidence that NORPROLAC has any embryotoxic or teratogenic potential, but experience in pregnant women is still limited. In patients wishing to conceive, NORPROLAC should be discontinued when pregnancy is confirmed, unless there is a medical reason for continuing therapy. No increased incidence of abortion has been observed following withdrawal of the drug at this point.

If pregnancy occurs in the presence of a pituitary adenoma and NORPROLAC treatment has been stopped, close supervision throughout pregnancy is essential.

Lactation

Breast-feeding is usually not possible since NORPROLAC suppresses lactation. If lactation should continue during treatment, breast-feeding cannot be recommended because it is not known whether quinagolide passes into human breast milk.

4.7. Effects on ability to drive and use machines

Since, especially during the first days of treatment, hypotensive reactions may occasionally occur and result in reduced alertness, patients should be cautious when driving a vehicle or operating machinery.

Patients being treated with NORPROLAC and presenting with somnolence must be advised not to drive or engage in activities where impaired alertness may put themselves or others at risk of serious injury or death (e.g. operating machines) unless patients have overcome such experiences of somnolence (see 4.4 Special warnings and precautions for use).

4.8. Undesirable effects

Frequency estimate: very common ≥10%, common ≥1% to <10%, uncommon ≥0.1% to <1%, rare ≥0.01% to <0.1%, very rare <0.01%.

The adverse reactions reported with the use of NORPROLAC are characteristic for dopamine receptor agonist therapy. They are usually not sufficiently serious to require discontinuation of treatment and tend to disappear when treatment is continued.

Very common undesirable effects are nausea, vomiting, headache, dizziness and fatigue. They occur predominantly during the first few days of the initial treatment or, as a mostly transient event, following dosage increase. If necessary, nausea and vomiting may be prevented by the intake of a peripheral dopaminergic antagonist, such as domperidone, for a few days, at least 1 hour before ingestion of NORPROLAC.

Common undesirable effects include anorexia, abdominal pain, constipation or diarrhoea, insomnia, oedema, flushing, nasal congestion and hypotension. Orthostatic hypotension may result in faintness or syncope (see 4.4 Special warnings and precautions for use).

Rarely NORPROLAC has been associated with somnolence.

In very rare cases, treatment with NORPROLAC has been associated with the occurrence of acute psychosis, reversible upon discontinuation.

Impulse control disorders

Pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists including NORPROLAC. (See section 4.4. 'Special warnings and precautions for use').

4.9. Overdose

Symptoms: Acute overdosage with NORPROLAC tablets has not been reported. It would be expected to cause severe nausea, vomiting, headache, dizziness, drowsiness, hypotension and possibly collapse. Hallucinations could also occur.

Treatment: Should be symptomatic.