Consumer medicine information

Parlodel

Bromocriptine

BRAND INFORMATION

Brand name

Parlodel

Active ingredient

Bromocriptine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Parlodel.

What is in this leaflet

This leaflet answers some common questions about Parlodel.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

The information in this leaflet was last updated on the date listed on the final page. More recent information on the medicine may be available.

You should ensure that you speak to your pharmacist or doctor to obtain the most up to date information on the medicine. Those updates may contain important information about the medicine and its use of which you should be aware.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Parlodel against the benefits they expect it will provide.

If you have any concerns about this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What Parlodel is used for

Parlodel has several uses. It can be used for the following medical conditions:

  1. Prevention/suppression of breast milk production (lactation) in women who cannot/do not breast-feed for medical reasons. If breast milk production has already begun, your doctor can advise you about other methods of stopping lactation.
  2. Treatment of people who have high blood levels of a hormone called prolactin. This condition is sometimes caused by a type of tumour called a prolactinoma.
  3. Treatment of acromegaly, a disease in which the body produces too much growth hormone. Parlodel treats this disease by reducing the level of growth hormone in the blood.
  4. To relieve symptoms, such as shaking of the limbs, stiffness and slowness of movement, in people with Parkinson's disease. Parlodel is often used in combination with other medicines such as levodopa.

Parlodel contains the active ingredient, bromocriptine. It belongs to a group of medicines known as the ergot alkaloids, derived from a type of fungus.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

This medicine is only available with a doctor's prescription. It is not addictive.

Parlodel may be used with caution in older people.

There is not enough information to recommend this medicine for children.

Before you take Parlodel

When you must not take it

Do not take Parlodel if you have an allergy to:

  • bromocriptine (the active ingredient) or any of the other ingredients of Parlodel listed at the end of this leaflet
  • any other medicines containing ergot alkaloids.

Some of the symptoms of an allergic reaction may include shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue or other parts of the body; rash, itching or hives on the skin.

Do not take Parlodel if you have any of the following medical conditions:

  • high blood pressure that is not controlled (uncontrolled hypertension)
  • toxaemia during pregnancy or immediately after giving birth, with symptoms such as high blood pressure, fluid build-up and convulsions
  • severe heart disease
  • mental illness now or in the past

If you are not sure whether any of the above conditions apply to you, your doctor can advise you.

Do not take Parlodel after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. In that case, return it to your pharmacist.

Before you start to take it

Tell your doctor if you have any of the following health problems / medical conditions:

  • diabetes
  • problems with your liver
  • black stools or stomach ulcers
  • problems with blood circulation
  • excessive drowsiness, or if you unexpectedly fall asleep

Your doctor may want to take special precautions if you have any of the above conditions.

Tell your doctor if you are pregnant or intend to become pregnant. Your doctor can discuss the benefits and any risks of taking this medicine during pregnancy.

Tell your doctor if you are breast-feeding or intend to breast-feed. Parlodel prevents the production of breast-milk due to its effects on prolactin.

Tell your doctor if you are lactose intolerant. This medicine contains lactose.

Tell your doctor if you are allergic to any other medicines, foods, dyes or preservatives. Your doctor will want to know if you are prone to allergies.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you buy without a prescription from a pharmacy, supermarket or health food shop.

Some medicines and Parlodel may interfere with one another. These include:

  • other medicines containing ergot alkaloids, such as medicines used to treat migraine headaches
  • medicines used to treat high blood pressure
  • any other medicine that may either raise or lower blood pressure
  • levodopa, a medicine for Parkinson's disease
  • some antibiotics, used to treat infections, such as erythromycin
  • octreotide, a medicine used to treat acromegaly and certain tumours
  • medicines used to treat HIV/AIDS, such as ritonavir, nelfinavir, indinavir, and delavirdine.
  • medicines used to treat fungal infections such as ketoconazole, itraconazole, and voriconazole.
  • dopamine antagonists, such as phenothiazines, butyrophenones thioxanthenes, metoclopramide, and domperidone.
  • phenylpropanolamine (a medicine used to treat nasal congestion)
  • bromocriptine, a medicine used to treat Parkinson's disease.
  • sumatriptan, a medicine used to treat migraine.
  • ergot alkaloids, medicines used to treat migraine and post-delivery bleeding.

You may need to take different amounts of your medicines or to take different medicines while you are taking Parlodel. Your doctor and pharmacist have more information.

If you have not told your doctor about any of these things, tell him/her before you start taking this medicine.

How to take Parlodel

Follow all directions given to you by your doctor and pharmacist carefully. These instructions may differ from the information contained in this leaflet.

If you do not understand the instructions on the label, ask your doctor or pharmacist for help.

How much to take

Parlodel is available as 2.5 mg tablets.

The dose that your doctor prescribes will depend on your condition.

  1. To prevent breast milk production, one tablet is taken twice daily for 2 weeks. Sometimes milk production will start again 2 or 3 days after the medicine is finished. A further 1 week course of Parlodel will usually bring this under control.
  2. To lower prolactin levels, treatment usually starts with half a tablet two to three times a day. If necessary, this dose may be gradually increased to one tablet three times each day. If the high prolactin levels are caused by a prolactinoma, the dose may be increased up to 15 mg daily, usually divided into 2 to 4 doses.
  3. For acromegaly, treatment usually starts with half a tablet each night. The dose is then slowly increased over a period of 1 to 2 weeks to one tablet four times a day. The dose can be further increased if needed. Most people need between 10 mg and 30 mg per day. The maximum dose is not usually more than 40 mg per day.
  4. For Parkinson's disease, treatment usually starts with half a tablet once or twice a day for the first week. The dose may be increased by half a tablet per week until the best effect is achieved. Most people need between 5 mg and 40 mg per day in 3 or 4 divided doses.

How to take it

When you start to take Parlodel, take the first dose with a snack just before bedtime. After you start taking the medicine, be careful to get up slowly from a sitting or lying position. Parlodel can make you dizzy, lightheaded or faint, especially when you first take it. This is because your blood pressure has suddenly dropped. Taking the first dose at bedtime and being careful when standing up will help your body get used to the change in blood pressure and will reduce the risk of falling.

After the first dose of Parlodel, take the tablets or capsules at mealtime with a full glass of water. Taking Parlodel with food helps to reduce stomach irritation and nausea.

Take the medicine at about the same times each day. Taking the doses at the same times each day will have the best effect. It will also help you to remember to take them.

How long to take it

Continue taking Parlodel for as long as your doctor recommends. Your doctor will check your progress to make sure the medicine is working and will discuss with you how long your treatment should continue.

If you forget to take it

If it is almost time for your next dose, skip the dose you missed and take the next dose when you are meant to.

Otherwise, take it as soon as you remember, and then go back to taking it as you would normally.

Do not take a double dose to make up for the one that you missed. This may increase the chance of you getting an unwanted side effect.

If you have trouble remembering when to take your medicine, ask your pharmacist for some hints.

If you take too much (Overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone number 13 11 26), or go to Accident and Emergency at your nearest hospital if you think that you or anyone else may have taken too much Parlodel. Do this even if there are no signs of discomfort or poisoning. Keep the telephone numbers for these places handy.

Some of the symptoms of an overdose may include nausea, vomiting, sleepiness, dizziness, lightheadedness, hallucinations (seeing or hearing things that are not there).

While you are taking Parlodel

Things you must do

Do not use Parlodel if you are breast feeding. Women who have taken Parlodel after childbirth or abortion have experienced some rare, serious side effects. These include fits, high blood pressure, stroke, heart attack and mental disorders.

If you are taking Parlodel to lower prolactin levels and you do not wish to become pregnant, you must use a reliable means of contraception. As your prolactin levels become lower, your menstrual periods may return to normal and you could become pregnant.

Keep all of your doctor's appointments so that your progress can be checked. Your doctor may want to do some tests from time to time to make sure the treatment is working and to prevent unwanted side effects from happening.

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking Parlodel.

Tell any other doctor, dentist or pharmacist who treats you that you are taking Parlodel.

Things you must not do

Do not give this medicine to anyone else even if their condition seems similar to yours.

Do not take it to treat any other complaints unless your doctor tells you to.

Things to be careful of

Be careful driving, operating machinery or doing jobs that require you to be alert until you know how Parlodel affects you. This medicine may make you feel dizzy, lightheaded or faint, especially when you first take it. It may also cause confusion and mental changes in a few people. Very rarely it can cause extreme sleepiness and sudden onset of sleep in the middle of daytime activities, sometimes without warning.

If you have any of these symptoms, do not drive or do anything else that could be dangerous.

Be careful when drinking alcohol while taking Parlodel. The combination may cause unwanted side effects. Your tolerance for alcohol may be lower than usual.

Tell your doctor or caregiver if you notice any unusual behavioural changes. Some impulse control disorders have been reported in patients treated with high doses of this medicine. These may include an increased sexual drive, a failure to control gambling, or failure to resist a temptation, urge, or impulse.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Parlodel. As with all medicines, patients treated with Parlodel can have side effects, although not everyone gets them. Sometimes they are serious, but most of the time they are not. You may need medical treatment if you get some of the side effects.

Some of the side effects listed below are more common at the beginning of treatment and may disappear as treatment continues. Your doctor may be able to reduce some side effects by lowering your dose of Parlodel.

Do not be alarmed by these lists of possible side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following side effects and they worry you:

  • nausea or vomiting
  • dizziness or light headedness, especially on standing up
  • drowsiness or sleepiness (if you have extreme sleepiness or sudden onset of sleep in the middle of daytime activities, tell your doctor immediately)
  • unexplained shortness of breath or difficulty breathing
  • severe, progressive, or persistent headaches
  • tiredness
  • sinus congestion
  • constipation
  • diarrhoea
  • nervousness
  • difficulty sleeping or restlessness
  • physical excitement or muscular activity associated with anxiety or mental tension (such as pacing, tapping of feet, or another repeated action)
  • feeling unsteady on your feet
  • depression (sad mood)
  • loss of appetite
  • dry mouth, metallic taste
  • sore eyes or blurred vision
  • hair loss
  • burning sensation in the breasts
  • leg cramps or burning feeling in the feet
  • painful, tingling or pale fingers and toes when exposed to cold
  • buzzing, hissing, whistling, ringing or other persistent noise in the ears
  • uncontrolled body movements (such as uncontrollable twitching, jerking or writhing)
  • an irregular, slow, or fast heart beat
  • heartburn, recurrent stomach pain
  • swelling of the arms or feet due to fluid build up
  • sudden watery discharge from your nose
  • skin rash or itchiness
  • lower back pain, swollen legs and pain when passing urine
  • behavioural changes such as self-harm, urge to gamble, failure to resist a temptation or impulse, or increased sexual drive
  • strange or disturbing thoughts or moods

Tell your doctor immediately or go to Accident and Emergency at your nearest hospital if you develop:

  • severe persistent headache or vision problems. Some women who have taken Parlodel to prevent breast milk production have had seizures (fits), high blood pressure, stroke, heart attack, or mental disorders. It is not known whether these problems are caused by Parlodel or are complications of giving birth.
  • any signs of stomach bleeding such as red or black bowel motions, bloody diarrhoea, bleeding from the back passage or vomiting blood. Some people being treated with high doses of Parlodel for acromegaly have had serious stomach bleeding.
  • confusion, hallucinations (seeing or hearing things that are not there) or sudden sleep attacks. Some people being treated with Parlodel for Parkinson's disease, especially with high doses, have experienced mental changes.
  • muscle stiffness, agitation, very high fever, or heart problems.
  • wheezing, cough or other breathing problems, chest pain, back pain, swelling of the feet or kidney problems while taking Parlodel.

When Parlodel is used for a long time to treat Parkinson's disease, it can affect the lungs, heart or abdomen. Your doctor may ask you to have regular chest x-rays to see if you are developing any problems.

Tell your doctor if you notice anything else that is making you feel unwell. Some people may have other side effects not yet known or mentioned in this leaflet.

After using Parlodel

Storage

  • Keep your medicine in the original container until it is time to take it
  • Store it in a cool dry place.
  • Do not store Parlodel or any other medicine in the bathroom or near a sink.
  • Do not leave it in the car or on window sills.

Keep the medicine where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking Parlodel or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

Parlodel 2.5 mg tablets are round white scored tablets marked with "XC" on one side and "SANDOZ" on the other side; packs of 30 tablets

Ingredients

Parlodel tablets contain 2.5 mg of the active ingredient, bromocriptine (as the mesilate salt). They also contain:

  • magnesium stearate
  • silica colloidal anhydrous
  • maize starch
  • disodium edetate
  • maleic acid
  • lactose

Allergens: This medicine contains lactose.

Other excipients with known effect: This medicine contains sugars.

Parlodel does not contain gluten, tartrazine or any other azo dyes.

Sponsor

Parlodel is supplied in Australia by:

Sandoz Pty Ltd
ABN 60 075 449 553
100 Pacific Highway
North Sydney, NSW 2060
Australia
Telephone 1800 726 369

®= Registered Trademark

This leaflet was prepared in November 2023.

Australian Registration Number:

2.5 mg tablet blister AUST R 13367

Published by MIMS February 2024

BRAND INFORMATION

Brand name

Parlodel

Active ingredient

Bromocriptine

Schedule

S4

 

1 Name of Medicine

Bromocriptine mesilate.

2 Qualitative and Quantitative Composition

Parlodel tablets and capsules contain bromocriptine mesilate.

Oral tablets.

2.5 mg bromocriptine (present as 2.9 mg mesilate).

Oral capsules.

10 mg bromocriptine (present as 11.5 mg mesilate).
5 mg bromocriptine (present at 5.735 mg mesilate).
List of excipients with known effect: lactose and sugars.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Oral tablets.

White, coded XC with breakline on one side, Sandoz on the other side.

Oral capsules.

5 mg: opaque white and opaque blue, marked PS.
10 mg: opaque white.

4 Clinical Particulars

4.1 Therapeutic Indications

Prevention of onset of lactation in the puerperium for clearly defined medical reasons. Therapy should be continued for 14 days to prevent rebound lactation. Parlodel should not be used to suppress established lactation.
Treatment of hyperprolactinaemia where surgery and/or radiotherapy are not indicated or have already been used with incomplete resolution. Precautions should be taken to ensure that the hyperprolactinaemia is not due to severe primary hypothyroidism. Where the cause of hyperprolactinaemia is a prolactin secreting microadenoma or macroadenoma, Parlodel is indicated for conservative treatment; prior to surgery in order to reduce tumour size and to facilitate removal; after surgery if prolactin level is still elevated.
Adjunctive therapy in the management of acromegaly when:
(1) The patient refuses surgery and/or radiotherapy;
(2) Surgery and/or radiotherapy has been unsuccessful or full effects are not expected for some months;
(3) A manifestation of the acromegaly needs to be brought under control pending surgery and/or radiotherapy.
Idiopathic or post-encephalitic Parkinson's disease. It should be noted that data are not yet sufficient to evaluate the role of Parlodel in treating early parkinsonism.

4.2 Dose and Method of Administration

The drug should always be taken with food since the incidence of nausea is reduced.

Inhibition of physiological lactation.

2.5 mg (1 tablet) twice daily with morning and evening meals for 14 days. To prevent the onset of lactation, treatment should be commenced as soon as possible after parturition but not until vital signs, especially blood pressure, have stabilised and not until four hours after delivery (see Section 4.4 Special Warnings and Precautions for Use, Hypotension). Secretion of milk may recur 2 to 3 days after the end of the treatment period. This can be controlled by resuming treatment at the same dosage for a further week.

Hyperprolactinaemia.

1.25 mg (½ tablet) 2 to 3 times daily. If this proves inadequate, gradually increase to 2.5 mg (1 tablet) 2 or 3 times daily with meals. If associated with galactorrhoea, continue treatment until breast secretion has completely disappeared and, if associated with amenorrhoea, until the menstrual cycle has returned to normal. If required, treatment may be continued over several menstrual cycles to prevent relapse. For the treatment of prolactinomas, Parlodel should be initiated at 1.25 mg (½ tablet) 2 times daily. If the dosage proves inadequate to reduce the serum prolactin level and reduce tumour size, gradually increase up to 15 mg daily in divided doses.

Adjunctive therapy in the management of acromegaly.

Initially 1.25 mg (½ tablet) at night, increasing gradually over a period of 1 to 2 weeks to 10 mg daily. Most acromegalics able to derive benefit from Parlodel do so at doses of 10 to 30 mg daily. Dosage should be adjusted appropriately, depending on clinical response and side effects. The daily dose should be taken in four equally divided doses with meals. It is recommended that a daily dose of 40 mg is not exceeded.

Parkinson's disease.

Anti-parkinson effects can be obtained with doses as low as 5 to 10 mg daily. The therapeutic range in either monotherapy or combined therapy is 5 to 40 mg/day in divided doses, usually at 6-8 hourly intervals. The best results may be achieved if the dosage is increased slowly, starting with 1.25 mg (½ tablet) once or twice a day (with meals) for the first week, followed by increments of not more than 1.25 mg every week, as monitored by therapeutic response and tolerability. When Parlodel is given in combination with levodopa, with or without a decarboxylase inhibitor, it may be possible to reduce the dose of levodopa. Any reduction in the dosage should be gradual. In certain cases, levodopa can be withdrawn completely.
The 10 mg capsule has yet to be established as bioequivalent with 4 x 2.5 mg tablets or 2 x 5 mg capsules.

4.3 Contraindications

Hypersensitivity to bromocriptine or other ergot alkaloids, hypersensitivity to any other component of the formulations (see Section 6.1 List of Excipients).
Uncontrolled hypertension, toxaemia, hypertensive disorders of pregnancy (including eclampsia, pre-eclampsia or pregnancy induced hypertension), hypertension postpartum and in the puerperium. For procedure during pregnancy see Section 4.6 Fertility, Pregnancy and Lactation.
Coronary artery disease and other severe cardiovascular conditions.
Symptoms and/or history of serious psychiatric disorders.

4.4 Special Warnings and Precautions for Use

General.

If women with conditions not associated with hyperprolactinaemia are treated with Parlodel, the drug should be given in the lowest effective dose necessary to relieve the symptoms; this is in order to avoid the possibility of suppressing plasma prolactin below normal levels, with a consequent impairment of luteal function.

Use in patients with prolactin secreting adenomas.

Since patients with macro-adenomas of the pituitary might have accompanying hypopituitarism due to compression or destruction of pituitary tissue, one should make a complete evaluation of pituitary functions and institute appropriate substitution therapy prior to administration of Parlodel. In patients with secondary adrenal insufficiency, substitution with corticosteroids is essential.
In some patients with macroprolactinoma, secondary deterioration of the visual fields may develop despite normalised prolactin levels and tumour shrinkage. This may result from traction on the optic chiasm, which is pulled down into the now partially empty sella. In these cases, the visual field defect may improve on reduction of Parlodel dosage, while there is some elevation of prolactin and some tumour re-expansion. Monitoring of visual fields in patients with macroprolactinoma is recommended to allow early recognition of secondary loss of visual fields due to chiasmal herniation and adaptation of drug dosage.
If pregnancy occurs in patients with adenomas after the administration of Parlodel, careful observation is mandatory (see Section 4.6 Fertility, Pregnancy and Lactation). Prolactin-secreting adenomas may expand during pregnancy. In severe cases, compression of the optic or other cranial nerves may necessitate emergency pituitary surgery.
In some patients with prolactin secreting adenomas treated with Parlodel, cerebrospinal fluid rhinorrhoea has been observed.

Psychiatric disturbances.

Parlodel, administered alone or concomitantly with levodopa for Parkinson's disease, may cause hallucinations (visual or auditory), which usually resolve with dosage reduction. Occasionally, discontinuation of Parlodel is required. Rarely after high doses, hallucinations have persisted for several weeks following discontinuation of Parlodel. High doses of Parlodel may be associated with confusion and mental disturbances. Since parkinsonian patients may manifest mild degrees of dementia, caution should be used when treating such patients.

Hypotension.

Parlodel is known to cause hypotension in some subjects. This usually manifests as postural hypotension and may be more common during initial dosing. Occasional reports have been made of collapse with hypotension and loss of consciousness within a few hours of taking initial doses of 1.25 to 2.5 mg.
For these reasons, treatment should be initiated with small doses and great care in all patients and especially in those with compromised cerebral or cardiac circulation. In post-partum patients, hypotension independent of drug therapy may already be present and Parlodel therapy for suppression of lactation should not be commenced until vital signs are stable, and no sooner than four hours after delivery.
Although there is no evidence of an interaction with antihypertensive agents, care should be exercised if Parlodel is administered with other medication known to lower blood pressure.

Gynaecological supervision.

Although there is no evidence of uterine tumour development in women receiving Parlodel, in view of the above-mentioned lifetime rat study, it is recommended that female patients on long-term therapy should have regular gynaecological assessments (see Section 5.3 Preclinical Safety Data, Carcinogenicity).

Peptic ulcer.

A few cases of gastrointestinal bleeding and gastric ulcer have been reported. Patients with a history or evidence of peptic ulceration should be closely monitored when receiving treatment in view of several reports of fatal gastric haemorrhage in acromegalic patients given high doses of bromocriptine. No causal relationship has been established between bromocriptine treatment and these findings, and gastric haemorrhage is known to occur in acromegalic patients. If bromocriptine must be used in such patients, they should be instructed to report any gastrointestinal side effects. If gastrointestinal bleeding or gastric ulceration occurs, bromocriptine should be withdrawn.

CNS effects.

Parlodel can have unwanted central actions such as dizziness, syncope, confusion and hallucinations, and particular care should, therefore, be exercised by patients driving vehicles, operating dangerous machinery or being pedestrians in busy areas.
Bromocriptine has been associated with somnolence and episodes of sudden sleep onset, particularly in patients with Parkinson's disease. Sudden onset of sleep during daily activities, in some cases without awareness or warning signs, has been reported very rarely. Patients must be informed of this and advised to exercise caution while driving or operating machines during treatment with bromocriptine. Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from driving or operating machines. Furthermore, a reduction of dosage or termination of therapy may be considered.

Diabetic retinopathy.

Parlodel may cause a release of growth hormone in normal and diabetic patients, lasting 1 to 2 hours. Growth hormone has been implicated in the acceleration or maintenance of diabetic retinopathy and Parlodel should, therefore, be used with caution in patients with diabetes.

Fibriotic conditions.

Among patients on Parlodel, particularly on long-term and high-dose treatment, pleural and pericardial effusions, as well as pleural and pulmonary fibrosis and constrictive pericarditis, have occasionally been reported. If long-term treatment is required, physicians should consider regular monitoring (e.g. chest X-rays). Patients presenting with unexplained pleuropulmonary signs or symptoms should be examined thoroughly and discontinuation of Parlodel therapy should be contemplated.
In a few patients on Parlodel, particularly on long-term and high-dose treatment, retroperitoneal fibrosis has been reported. To ensure recognition of retroperitoneal fibrosis at an early reversible stage, it is recommended that its manifestations (e.g. back pain, oedema of the lower limbs, impaired kidney function) be looked for in this category of patient. Parlodel should be withdrawn if fibrotic changes in the peritoneum are diagnosed or suspected.

Liver function.

The extensive hepatic metabolism of bromocriptine suggests that patients with impaired hepatic function should be treated with care. Dose adjustment may be required.

Galactose intolerance.

Patients with rare hereditary problems of galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption should not take Parlodel.

Impulse control disorders.

Patients should be regularly monitored for the development of impulse control disorders. Patients with carers should be made aware that compulsive behaviour such as pathological gambling, increased libido, hypersexuality, compulsive spending or shopping, binge eating, compulsive eating, medication use and punding (repetitive purposeless activity) has been reported in patients treated with dopamine agonists, including Parlodel, especially at high doses. Dose reduction/ tapered discontinuation should be considered if such symptoms develop.
Prescribers, patients and caregivers should be alert to the possibility of such behaviour, which may have serious financial and social consequences.

Renal impairment.

No studies have been performed in renally impaired patients.

Hepatic impairment.

No studies have been performed in hepatically impaired patients.

Use in the elderly.

Clinical studies for Parlodel did not include sufficient numbers of subjects aged 65 years and above to determine whether the elderly respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, starting at the lower end of the dose range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy in this population.

Paediatric use.

The use of Parlodel is not recommended for children.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Pharmacological considerations indicate there are a number of theoretically possible drug interactions.

Alcohol.

Tolerability to Parlodel (bromocriptine) may be reduced by alcohol.

Antihypertensives.

The hypotensive effects of bromocriptine may be additive with those of drugs used to treat hypertension and other medication known to lower blood pressure.

CYP3A4 substrates/ inhibitors.

Bromocriptine is both a substrate and an inhibitor of CYP3A4 (see Section 5.1 Pharmacodynamic Properties). Caution should, therefore, be used when co-administering drugs which are strong inhibitors and/or substrates of this enzyme (azole antimycotics, HIV protease inhibitors). The concomitant use of erythromycin, other macrolide antibiotics or octreotide has been shown to increase bromocriptine plasma levels. The bioavailability of bromocriptine increased by approximately 40% when it was administered together with octreotide.

Sympathomimetic drugs.

Co-administration of sympathomimetics such as phenylpropanolamine and bromocriptine may lead to hypertension and severe headache (see Section 4.4 Special Warnings and Precautions for Use).
For the concomitant use of sympathomimetic drugs in post-partum women, see Section 4.6 Fertility, Pregnancy and Lactation, Physiological lactation.

Sumatriptan.

Co-administration of sumatriptan may potentiate the risk of vasospastic reactions due to additive pharmacological effects.

Ergot alkaloids.

Co-administration may increase the dopamine stimulant activity and lead to dopaminergic side effects such as headache, nausea, vomiting (see Section 4.4 Special Warnings and Precautions for Use).

Dopamine receptor agonists.

Since Parlodel exerts its therapeutic effect by stimulating central dopamine receptors, dopamine antagonists such as antipsychotics (phenothiazines, butyrophenones and thioxanthenes), but also metoclopramide and domperidone may reduce its activity. The following drugs may increase prolactin secretion and possibly may antagonise Parlodel in a dose dependent manner: phenothiazines, butyrophenones, metoclopramide, methyldopa, reserpine, tricyclic antidepressants, pimozide, oestrogens, TRF. Other drugs may inhibit prolactin release from the pituitary and may be synergistic with Parlodel: levodopa, clonidine, pargyline, iproniazid.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

In patients being treated with Parlodel for hyperprolactinaemic conditions, fertility is commonly restored. The return of ovulation post-partum also may be hastened. Thus women who do not wish to conceive should take contraceptive measures in order to prevent an unintended pregnancy.
In women wishing to conceive, the cause of sterility and a search for pituitary adenoma should be made before starting Parlodel (bromocriptine) treatment. Pregnancy must be avoided if a significant or expanding pituitary adenoma is diagnosed. However, if pregnancy occurs in the presence of a pituitary adenoma and Parlodel treatment has stopped, close supervision throughout pregnancy is essential. In patients who show symptoms of a pronounced enlargement of a prolactinoma (e.g. headache or visual field deterioration), Parlodel treatment may be reinstituted. In other cases, surgery may be considered appropriate.
In the absence of a significant or expanding pituitary adenoma, and if the patient wishes to conceive, Parlodel should be stopped as soon as possible after conception.
(Category A)
Over 2,400 women are recorded as having taken bromocriptine during part of pregnancy. The reported incidence of congenital malformations and spontaneous abortions within this group of pregnancies did not exceed that generally reported in the population at large.
Postnatal development was studied in more than 900 children exposed to bromocriptine in utero. One hundred and five of these children were exposed throughout pregnancy. No specific pattern of abnormal postnatal development could be recognised.
In patients wishing to conceive, however, Parlodel, like all drugs, should be discontinued when pregnancy is confirmed, unless there is a medical reason for continuing therapy.
If pregnancy occurs in the presence of a pituitary adenoma and Parlodel treatment has been stopped, close supervision throughout pregnancy is essential. In patients who show symptoms of a pronounced enlargement of a prolactinoma, e.g. headache or visual field deterioration, Parlodel treatment may be re-instituted or surgery may be appropriate.

Established pregnancy.

In cases of established pregnancy - as a precautionary measure - possible untoward effects of pituitary enlargement associated with pregnancy should be sought regularly, for instance, by checking the visual fields.
 Since Parlodel prevents lactation, Parlodel should not be administered to mothers who wish to breast-feed.

Physiological lactation.

In rare cases, serious adverse reactions have been reported in postpartum women treated with Parlodel for the inhibition of lactation, including seizures, stroke, myocardial infarction, hypertension and psychiatric disorders. Seizures were not necessarily accompanied by the development of hypertension. An unremitting and often progressively severe headache, sometimes accompanied by visual disturbance (blurred vision and transient cortical blindness), often preceded by hours to days the occurrence of seizure and/or stroke. Most patients had shown no evidence of toxaemia during the pregnancy.
Although the relationship of these adverse reactions to Parlodel administration is not certain, periodic monitoring of blood pressure is advisable in post-partum women receiving Parlodel for the inhibition of lactation as well as in patients treated for any other condition.
The use of Parlodel is contraindicated in patients with uncontrolled hypertension, coronary artery disease, toxaemia of pregnancy or symptoms and/or a history of serious psychiatric disorders.
Particular attention should be paid to patients who have recently received or are on concomitant therapy with other drugs that can alter the blood pressure, e.g. vasoconstrictors such as sympathomimetics or ergot alkaloids, including ergometrine. The concomitant use of these medications in the puerperium is not recommended.
Parlodel therapy for the inhibition of lactation should not be initiated until the vital signs have been stabilised and no sooner than four hours after delivery, as Parlodel is known to produce hypotension, and rarely hypertension, in some patients. Because the development of hypertension may be delayed, the blood pressure should be monitored periodically during the first weeks of therapy. If hypertension, severe, progressive or unremitting headache (with or without visual disturbance), or evidence of CNS toxicity develops, drug therapy should be discontinued and the patient should be evaluated promptly.

4.7 Effects on Ability to Drive and Use Machines

Since, especially during the first days of treatment, hypotensive reactions may occur and result in decreased alertness, particular care should be exercised when driving a vehicle or operating machinery (see Section 4.4 Special Warnings and Precautions for Use, Hypotension).
Bromocriptine has been associated with somnolence and/or episodes of sudden sleep onset, particularly in patients with Parkinson's disease. Sudden onset of sleep during daily activities, in some cases without awareness or warning signs, has been reported very rarely. Patients must be informed of this and advised not to drive, operate machines, or engage in activities where impaired alertness may put themselves or others at risk of serious injury or death until such recurrent episodes and somnolence have resolved (see Section 4.4 Special Warnings and Precautions for Use, CNS effects). Furthermore, a reduction of dosage and termination of therapy may be considered.

4.8 Adverse Effects (Undesirable Effects)

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.
The following adverse drug reactions with Parlodel have been derived from multiple sources including clinical trial and post-marketing experience via spontaneous case reports and literature cases (Table 1) are listed by MedDRA system organ class. Within each system organ class, the adverse drug reactions are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each adverse drug reaction is based on the following convention (CIOMS III): very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, < 1/1,000) very rare (< 1/10,000) and unknown.
During the first days of treatment, patients commonly experience nausea, dizziness or headache and, less frequently, nasal congestion, fatigue or vomiting, not usually sufficiently serious to require treatment to be discontinued. Bromocriptine frequently causes a reduction in blood pressure, manifested as postural hypotension (very rarely leading to syncope).
The spectrum and incidence of side effects occurring in Parkinson's patients differs somewhat from that found in patients being treated for endocrinological indications. It should be noted that, to date, clinical experience of bromocriptine in Parkinson's disease has generally followed or been associated with other therapy. Hallucinations, confusion and behavioural disturbances have been reported commonly in patients receiving doses above 15 mg/day. Delusions, psychotic episodes (including paranoia) and delirium are less frequent. Psychotic episodes have also occurred at 2.5 to 5.0 mg daily. Dyskinesias or abnormal involuntary movements and "on-off" effect have been reported in patients treated for Parkinson's disease but, to date, there is no adequate experience of patients who have been treated only with Parlodel. Pleuro-pulmonary changes (pleural and pericardial effusions, pleural and pulmonary fibrosis), constrictive pericarditis and retroperitoneal fibrosis have occurred in patients on long-term therapy (see Section 4.4 Special Warnings and Precautions for Use).
In several acromegalic patients treated with high doses, fatal gastric haemorrhage has been reported (see Section 4.4 Special Warnings and Precautions for Use).
Episodes of reversible pallor of the fingers and toes induced by cold have occasionally been reported during prolonged treatment, particularly in patients previously exhibiting Raynaud's phenomenon.
The use of Parlodel for the inhibition of physiological lactation post-partum has been associated with the rare occurrence of hypertension, myocardial infarction, seizures, stroke and psychiatric disorders (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use).
Less frequently, ataxia, depression, anorexia, dyskinesia, erythromelalgia, metallic taste, decreased alcohol tolerance, diplopia, eye discomfort, cardiac arrhythmias, epigastric pain, oedema, urticaria and other rashes, and a burning sensation in the breast have also been reported. These side effects are usually dose dependent and can in most cases be controlled by a reduction in dosage.
Bromocriptine has been associated very rarely with excessive daytime somnolence and sudden sleep onset episodes (see Section 4.4 Special Warnings and Precautions for Use, CNS effects).

4.9 Overdose

There have been isolated reports of children who accidentally ingested Parlodel. Vomiting, somnolence and fever were reported as adverse events. Patients recovered either spontaneously within a few hours or after appropriate management.
Several reports have been made to the company of acute overdosage with Parlodel which, however, were mainly within the therapeutic range. There were no life threatening reactions. Symptoms reported could have resulted from overstimulation of dopaminergic receptors. The observed symptoms of overdosage include nausea, vomiting, dizziness, drowsiness, lethargy, somnolence, tachycardia, hypotension and postural hypotension. In addition, psychotic reactions and hallucinations may also occur.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Parlodel has a pharmacological spectrum unlike that of most classical ergot compounds, having no uterotonic and little vasoconstrictor activity. Its principal effects derive from dopaminergic receptor stimulant activity. It inhibits prolactin secretion and the effect can be demonstrated after single or repeated oral administration of the drug. Moreover, the effect is relatively specific in that doses necessary to produce inhibition of prolactin secretion do not interfere with release of gonadotrophins or thyrotrophin. However, Parlodel elevates growth hormone for a few hours after each dose in normal or diabetic persons. This may not be reflected by an elevation of basal levels during chronic administration. However, it may suppress the elevated growth hormone levels of acromegalic patients.
Parlodel has been shown to arrest the growth or to reduce the size of prolactin-secreting pituitary adenomas (prolactinomas).
Pharmacological investigations in rodent brains show that, in addition to its effects at the hypothalamic-pituitary axis, Parlodel exerts CNS activity primarily via post-synaptic dopamine receptor activation in the corpus striatum. Parlodel can, therefore, be used in Parkinson's disease.

Clinical trials.

Hyperprolactinaemia.

Prolactin secretion is controlled by the hypothalamic tuberoinfundibular dopaminergic neurone system, which releases either dopamine or a prolactin inhibiting factor (PIF) into the hypothalamohypophyseal portal system to suppress the secretion of prolactin by the pituitary. Parlodel has been shown to mimic this action of dopamine on the pituitary prolactin cells and to act also at the hypothalamic level.
Prolactin is the crucial hormone for the preparation of the mammary gland for lactation and for the initiation and maintenance of milk secretion. During pregnancy and after childbirth (through suckling stimuli) prolactin levels are elevated. Reduction of circulating prolactin levels will thus prevent or suppress lactation. In some conditions, the secretion of prolactin may become elevated in situations unconnected with pregnancy and childbirth. Such nonphysiological hyperprolactinaemia may mimic the postpartum situation by inducing amenorrhoea and/or lactation (galactorrhoea). In healthy women, prolactin does not seem to be involved in the normal cycle of gonadotrophin secretion and ovarian functions but, in conditions favouring prolactin secretion, the regular cyclic gonadotrophin and gonadal steroid secretion become attenuated and are eventually suppressed. Bromocriptine, through its dopaminergic activity, returns prolactin levels towards normal and either enhances the release of gonadotrophic hormones or restores the sensitivity of the ovary to gonadotrophic stimulation.
Hence, galactorrhoea and amenorrhoea are interrupted and menses return.
Apparent regression in tumour size has been documented in a number of patients with prolactin-secreting adenomas.

Acromegaly.

In about 50% of acromegalic patients, Parlodel reduced the elevated growth hormone level to half of pretreatment levels or below. In acromegaly, Parlodel has a beneficial effect on clinical symptoms, such as headaches, sweating, acral features, ring and shoe size, hypertension and glucose tolerance, although this may not be clearly correlated with a change in growth hormone levels. Overall, about 50% of patients have shown clinical improvement to Parlodel. Of the remaining patients, many have a significant fall in growth hormone levels not associated with improvements in clinical symptoms.
There are no data on the effect of bromocriptine on tumour size in acromegaly or on the functional capacity of the tumour. There is some evidence that the acromegalic process resumes on cessation of therapy.

Parkinson's disease.

This disorder is characterised by progressive deficiency in dopamine synthesis in the substantia nigra. Parlodel produces its therapeutic effect by directly acting on dopamine receptors in the corpus striatum, mimicking an increased supply of endogenous dopamine. In clinical studies, Parlodel has been as effective as levodopa alone or in combination with decarboxylase inhibitors. Combination with levodopa may allow a reduction in the dosage of either compound. Bromocriptine is useful in patients with a deteriorating response to levodopa or suffering from the "on-off" phenomena. Parlodel may be given alone in mild, early cases or in combination with anticholinergic drugs and/or other antiparkinson drugs. However, data are not yet sufficient to evaluate the role of Parlodel in treating early parkinsonism.

5.2 Pharmacokinetic Properties

Absorption.

In rats, rabbits, monkeys and man, Parlodel has been shown to be rapidly absorbed after oral administration. In man, the absorption half-life from the oral tablet formulation determined by radioimmunoassay is approximately 0.3 hours. About 7% of the dose reaches the systemic circulation unchanged. This is due to a high hepatic extraction rate and first pass metabolism. The studies were done on fasting subjects. There are no studies on the effect of food on bioavailability, but clinical experience suggests that absorption is satisfactory when bromocriptine is taken in the recommended way (i.e. with meals).

Distribution.

Two hours after oral administration of 3H-bromocriptine in the rat, radioactivity was found in all organs, with highest values in the liver, stomach and intestine. Plasma protein binding amounts to 96%.

Metabolism.

In man, the substance is extensively metabolised by the liver. Only traces of the unchanged compound were found in urine, with 2 major metabolites. Unchanged drug represents about 10-15% of peak levels of radioactivity in plasma, measured after single doses of labelled drug. It is not known whether the metabolites are pharmacologically active in man. However the two main urinary metabolites, 2-bromolysergic acid and 2-bromoisolysergic acid have negligible pharmacological activity in animals.

Excretion.

The active parent drug and the metabolites are excreted primarily via the liver into the bile; only 6% is eliminated via the kidney. After single oral doses, the mean elimination half-life from plasma varies from 2 to 8 hours for the parent drug and 50 to 73 hours for the metabolites.
On repeated dosing, bromocriptine accumulates to the extent that plasma concentrations may be about twice those observed after single doses. Although there are no data on the accumulation of metabolites, their much longer half-life indicates that steady-state plasma concentrations, which are about ten times greater than those observed after single doses, should be reached in approximately 10 days.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

A lifetime rat study revealed that some animals developed uterine tumours and endometrial carcinoma, thought to be due to a state of induced oestrogen dominance. However, clinical experience in women with a variety of hyperprolactinaemic and other conditions, treated with bromocriptine for months and in some cases for years, failed to demonstrate abnormal trends in hormonal levels or in endometrial cytology.

6 Pharmaceutical Particulars

6.1 List of Excipients

Tablets.

Magnesium stearate, colloidal anhydrous silica, maize starch, disodium edetate, maleic acid, and lactose monohydrate.

Capsules.

Magnesium stearate, colloidal anhydrous silica, maize starch, maleic acid, lactose monohydrate, gelatin and titanium dioxide. The 5 mg capsules also contain shellac, iron oxide red, and indigo carmine.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Tablets: Store below 25°C. Protect from light.
Capsules*: Store below 25°C. Protect from light; Protect from moisture.
* Not all presentations are available.

6.5 Nature and Contents of Container

Oral tablets.

Parlodel bromocriptine 2.5 mg (as mesilate) tablet in PVC/PVDC/Al blister pack; 30's, 60's.
Parlodel bromocriptine 2.5 mg (as mesilate) tablet in HDPE bottle; 60's.

Oral capsules.

Parlodel bromocriptine 5 mg (as mesilate) capsule in coloured Type III glass bottle; 60's.
Parlodel bromocriptine 10 mg (as mesilate) capsule in coloured Type III glass bottle; 100's.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking it to your local pharmacy.

6.7 Physicochemical Properties

Bromocriptine mesilate is a peptide ergot alkaloid, poorly soluble in water (< 0.1% at 20 to 25°C).
Freely soluble in methanol. Solubility in ethanol (70% v/v) is 75%.

Chemical structure.


Chemical names: ergotaman-3',6',18-trione, 2-bromo-12'-hydroxy-2'-(1-methylethyl)-5'-(2-methylpropyl)-, (5'α)-;
2-bromoergocryptine monomethanesulphonate;
2-bromo-α-ergocryptine mesilate.
Chemical formula: C32H40BrN5O5CH4O3S.
Molecular weight: 750.7 (mesilate salt); 654.5 (free base).

CAS number.

22260-51-1.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes