Active ingredients: Bromocriptine
PARLODEL 5 mg hard capsules
PARLODEL 10 mg hard capsules
Parlodel package leaflets are available for pack sizes: - PARLODEL 5 mg hard capsules, PARLODEL 10 mg hard capsules
- PARLODEL 2.5 mg tablets
Indications Why is Parlodel used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Dopaminergic agonist.
THERAPEUTIC INDICATIONS
Idiopathic, arteriosclerotic, post-encephalitic Parkinson's disease.
PARLODEL is also indicated in patients whose therapeutic response to levodopa is fading, and in cases where the appearance of the "on-off" phenomenon limits the success of therapy with levodopa.
Contraindications When Parlodel should not be used
Hypersensitivity to the active substance, to any of the excipients (see "Composition") or to other ergot alkaloids.
Bromocriptine is contraindicated in patients with uncontrolled hypertension, hypertensive disorders of pregnancy (including eclampsia, pre-eclampsia or pregnancy-induced hypertension), postpartum and postpartum hypertension.
Bromocriptine is contraindicated for use in the suppression of lactation, or other non-life threatening indications, in patients with a history of coronary artery disease or other serious cardiovascular conditions, or symptoms / history of severe psychiatric disorders. of treatment with PARLODEL for a long time in patients who have or have had fibrotic (scar tissue) reactions affecting the heart.
Precautions for use What you need to know before taking Parlodel
The high doses of PARLODEL required for the treatment of Parkinson's disease, i.e. 10-20 mg / day or more, should not be used in other indications.
The treatment must be carried out under medical supervision.
If women with conditions not related to hyperprolactinemia are treated with PARLODEL, the drug should be administered at the lowest effective dose, necessary to relieve symptoms, in order to avoid the possibility of lowering the prolactin levels below normal, with a consequent alteration of the luteal function. Such patients should have plasma prolactin and post-ovulatory progesterone determinations at regular intervals if treatment continues for more than 6 months.
Some reports of gastrointestinal bleeding and gastric ulcer have been reported. In case of occurrence, the administration of PARLODEL should be discontinued. Patients with a history of peptic ulcer or current peptic ulcer should preferably receive alternative treatment. If PARLODEL is to be necessarily used in parkinsonian patients with acromegaly, they should be advised to promptly report any gastrointestinal reactions.
Since hypotensive reactions may occasionally arise, especially during the first days of treatment, leading to a decrease in alertness, particular care must be taken when driving vehicles or using machines (see also "Special warnings - Effects on the ability to drive or drive vehicles. on "use of machines") .. For the same reason, in outpatients it is advisable to monitor blood pressure values during the first days of treatment.
Bromocriptine has been associated with somnolence and episodes of sudden sleep onset, particularly in patients with Parkinson's disease.
Sudden sleep attacks have been reported very rarely during daily activity, in some cases without awareness and no warning signs. Patients taking bromocriptine should be informed of these events and advised to use caution while driving or operating machinery. . Patients who have experienced episodes of somnolence and / or a sudden episode of sleep should refrain from driving and using machines (see also "Special warnings - Effects on ability to drive or" use machines "). In addition, a reduction in dosage or discontinuation of therapy may be considered.
Pleural and pericardial effusions, as well as pleural and pulmonary fibrosis and constrictive pericarditis have occasionally been reported among patients treated with bromocriptine, particularly long-term and at high doses. Patients with pleuropulmonary disorders of an undetermined nature should be carefully examined and a "discontinuation of PARLODEL treatment should be considered.
Retroperitoneal fibrosis has been reported in some patients treated long-term and at high doses with PARLODEL. In order to ensure the recognition of retroperitoneal fibrosis in an initial reversible stage, in this type of patients it is recommended to monitor the typical symptoms of this pathology (eg: back pain, edema of the lower limbs, alterations in renal function). The use of PARLODEL should be discontinued if fibrotic changes of the retroperitoneum are diagnosed or suspected.
In subjects with galactorrhea, prolactin-dependent amenorrhea, menstrual disorders or acromegaly, treatment with PARLODEL can eliminate pre-existing infertility. Women, therefore, who could thus become fertile, but who do not wish to become pregnant should adopt a method of mechanical contraception. Before starting treatment with PARLODEL, the cause of infertility must be defined.
Pregnancy should be avoided if a diagnosis of pituitary adenoma is made. A marked enlargement of the sella turcica or a visual field defect requires surgical and / or radiotherapy treatment in the first instance. PARLODEL is only indicated if these measures have failed. In the absence of pituitary adenoma and if the patient is anxious to conceive, PARLODEL should be suspended as soon as possible after conception (early diagnosis of pregnancy with immunological test), since the knowledge on the possible effects of the drug on the evolution of pregnancy and on the fetus In cases of confirmed pregnancy, as a precautionary measure, the possible negative effects of a pituitary pathological event associated with pregnancy should be investigated regularly, for example by investigating the visual field.
Treatment in women should be under medical supervision including hormone dosage and gynecological examination. As good medical practice dictates, all women receiving PARLODEL continuously for more than 6 months should have regular gynecological checks at annual intervals if the woman is pre-menopausal, every 6 months if she is in menopause (cervical cytology and, if possible, endometrial).
Caution is required when PARLODEL is administered in high doses to Parkinsonian patients with a history of psychotic disorders, severe cardiovascular disease, peptic ulcer or gastrointestinal bleeding.
Use in postpartum women
Periodic monitoring of blood pressure is advisable in postpartum women treated with PARLODEL for any condition. In the event of hypertension, severe, progressive or incessant headache (with or without visual disturbance) or central nervous system toxicity, administration of PARLODEL should be discontinued and the patient promptly investigated.
Particular caution is required in patients who have recently been treated or are on concomitant therapy with drugs that can alter blood pressure, e.g. vasoconstrictors such as sympathomimetics or ergot alkaloids, including ergometrine or methylergometrine, and their concomitant use in the non-puerperium period. recommended.
Use in patients with impaired hepatic function
In patients with impaired hepatic function the rate of elimination may be delayed and plasma levels may increase requiring dosage adjustment.
Tell your doctor if you or someone in your family, or caregiver, notices that urges or desires are developing to behave in ways that are unusual for you and you cannot resist the urge or temptation to perform certain activities that could harm yourself or others. These are called impulse control disorders and can include behaviors such as gambling addiction, overeating, uncontrollable shopping or overspending, abnormal, exaggerated sex drive or increased thoughts sexual or feelings. Your doctor may find it necessary to change or discontinue your dose.
Interactions Which drugs or foods may change the effect of Parlodel
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
The possibility of interaction between bromocriptine and psychoactive or hypotensive drugs cannot be excluded.
Particular caution should be taken in patients being treated with ergot alkaloids or drugs that act on blood pressure in relation to a possible potential effect.
Bromocriptine is simultaneously a substrate and an inhibitor of cytochrome P3A4. Therefore, caution should be exercised when administering drugs that are strong inhibitors and / or substrates of this enzyme (azoline antifungals, HIV protease inhibitors).
Concomitant use of erythromycin, iosamycin or other macrolide antibiotics may increase the plasma levels of bromocriptine.
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 can reduce its activity.
Tolerability to treatment may be reduced by concomitant administration of alcohol.
Warnings It is important to know that:
Gambling, increased libido and hypersexuality have been reported in patients treated with dopamine agonists for Parkinson's disease including PARLODEL.
Pregnancy
Ask your doctor or pharmacist for advice if you have recently taken any other medicines, even those without a prescription.
In patients wishing to conceive, PARLODEL, like all other drugs, should be discontinued when pregnancy has been confirmed, unless there is a medical rationale for continuing therapy. No increased incidence of miscarriages was observed following discontinuation of PARLODEL therapy at this stage. Clinical experience indicates that PARLODEL, administered during pregnancy, does not adversely affect its course and outcome.
Feeding time
Since PARLODEL inhibits lactation, it should not be taken by mothers who wish to breastfeed.
Women of childbearing age
Treatment with PARLODEL can restore fertility. Women of childbearing age who do not wish to conceive should therefore be advised to practice a viable method of contraception.
Effects on ability to drive or use machines.
PARLODEL affects the ability to drive or use machines. Since, especially during the first days of treatment, hypotensive reactions may occasionally arise which lead to a reduction in alertness, particular attention must be paid when driving vehicles or using machinery.
Patients on bromocriptine treatment who experience episodes of drowsiness and / or sudden sleep attacks should be advised to refrain from driving or engaging in any activity in which impaired attention could expose themselves or others to the risk of serious harm or death. (eg using machines) until these recurrent episodes and sleepiness have resolved (see also "Precautions for use").
Information about some of the ingredients of PARLODEL
PARLODEL contains lactose. If your doctor has diagnosed you with "intolerance to some sugars, contact your doctor before taking this medicine.
Dosage and method of use How to use Parlodel: Dosage
The following dosing criteria apply only to the treatment of Parkinson's disease.
An antiparkinsonian effect is already observed at daily doses of 10-15 mg. The optimal dose range is usually higher (20 mg / day or more). The maximum daily dose is 30 mg / day. If PARLODEL is administered in combination with levodopa, with or without decarboxylase inhibitor, they may be sufficient. even lower doses The optimal dose should be reached with a slow and gradual increase in dosage.
An indicative dosage schedule can be the following: administer 2.5 mg twice a day for one week. Thereafter, the dose increase should not exceed 5 mg every 2-3 days.
Levodopa dose reductions should be made gradually until the optimal therapeutic effect is achieved: in some cases the treatment with levodopa can be completely suspended. For the gradual increase in dosage, PARLODEL 2.5 mg tablets are also available.
The drug should always be taken with meals.
Overdose What to do if you have taken too much Parlodel
Symptoms of overdose may include nausea, vomiting, dizziness, hypotension, postural hypotension, tachycardia, lethargy, somnolence, lethargy and hallucinations.
In case of accidental ingestion / intake of an excessive dose of PARLODEL, notify your doctor immediately or go to the nearest hospital.
If you have any questions about the use of PARLODEL, ask your doctor or pharmacist.
Side Effects What are the side effects of Parlodel
Like all medicines, PARLODEL can cause side effects although not everybody gets them.
Undesirable effects are listed according to frequency using the following convention: very common (≥ 1/10); common (≥ 1/100, <1/10); uncommon (≥ 1/1000, <1/100); rare (≥ 1 / 10,000, <1/1000); very rare (<1 / 10,000), including isolated cases:
Psychiatric disorders
Uncommon: Confusion, psychomotor agitation, hallucinations
Rare: Psychotic disorders; insomnia
Very rare: Increased libido, hypersexuality and gambling addiction
Nervous system disorders
Common: Headache, lethargy, dizzinessUncommon: Dyskinesia
Rare: Somnolence, paraesthesia
Very rare: Excessive sleepiness during the day, sudden sleep
Eye disorders
Rare: Visual disturbances, blurred vision
Ear and labyrinth disorders
Rare: Tinnitus
Cardiac disorders:
Rare: Pericardial effusion, constrictive pericarditis, tachycardia, bradycardia, arrhythmia
Very rare: Cardiac valvulopathy (including reflux) and related disorders (pleural and pericardial effusions)
Vascular pathologies
Uncommon: Hypotension, orthostatic hypotension (very rarely up to syncope)
Very rare: Reversible paleness of the fingers and toes caused by cold (mainly in patients with a history of Raynaud's phenomenon)
Respiratory, thoracic and mediastinal disorders
Common: Nasal congestion
Rare: Pleural effusions, pleural fibrosis, pleurisy, pulmonary fibrosis, dyspnoea
Gastrointestinal disorders
Common: Nausea, constipation, vomiting
Uncommon: Dry mouth
Rare: Diarrhea, abdominal pain, retroperitoneal fibrosis, gastrointestinal ulcer, gastrointestinal haemorrhage
Skin and subcutaneous tissue disorders
Uncommon: Allergic skin reactions, hair loss
Musculoskeletal and connective tissue disorders
Uncommon Leg cramps
General Disorders and Administration Site Site Conditions
Uncommon: Fatigue
Rare: Peripheral edema
Very rare: Neuroleptic Malignant Syndrome-like syndrome due to abrupt discontinuation of PARLODEL
Patients treated with dopamine agonists for Parkinson's disease including PARLODEL, especially at high doses, have reported the onset of gambling, increased libido and hypersexuality, generally reversible with reduction or discontinuation of treatment. These reports have been received very rarely with PARLODEL.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
If any or any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please inform your doctor or pharmacist.
The following side effects may occur:
Inability to resist the urge to take actions that could be harmful, which may include:
- strong urge to gamble excessively, despite serious personal or family consequences
- altered or increased sexual interest and behavior that causes you or others significant concern, such as increased sexual desire, uncontrollable shopping or overspending
- compulsive eating (eating large amounts of food in a short period of time) or bulimia (eating more food than normal and more than is needed to satisfy your hunger)
Tell your doctor if any of these behaviors occur so he can decide what to do to manage or reduce symptoms.
Expiry and Retention
Expiry: see the expiry date indicated on the package
The expiry date refers to the product in intact packaging, correctly stored.
CAUTION: DO NOT USE THE MEDICINAL PRODUCT AFTER THE EXPIRY DATE INDICATED ON THE PACKAGE.
storage
Do not store above 25 ° C.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
KEEP THE MEDICINAL PRODUCT OUT OF THE REACH AND SIGHT OF CHILDREN.
Composition and pharmaceutical form
COMPOSITION
PARLODEL 5 mg hard capsules
One capsule contains:
Active principle
bromocriptine mesylate 5.735 mg (equivalent to 5 mg of bromocriptine base.)
Excipients: Anhydrous colloidal silica, magnesium stearate, maleic acid, corn starch, lactose.
Constituents of the shell: Titanium dioxide, indigo carmine, gelatin.
PARLODEL 10 mg hard capsules
One capsule contains:
Active principle
bromocriptine mesylate 11,470 mg (equivalent to 10 mg of bromocriptine base).
Excipients: Anhydrous colloidal silica, magnesium stearate, maleic acid, corn starch, lactose.
Constituents of the shell: Titanium dioxide, gelatin.
PHARMACEUTICAL FORM and CONTENT
Capsules for oral use.
"5 mg hard capsules" - Box of 30 capsules
"10 mg hard capsules" - Box of 20 capsules.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
PARLODEL 2.5 MG TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains:
Active principle:
bromocriptine mesylate 2.87 mg, equivalent to 2.5 mg of bromocriptine base.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Tablets.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Galactorrhea with or without amenorrhea: idiopathic (Argonz del Castillo);
tumor (Forbes Albright); from drugs (psychotropics, contraceptives).
Prevention or suppression of postpartum physiological lactation only when clinically indicated (such as in the case of intrapartum loss, neonatal death, HIV infection, of the mother).
Bromocriptine is not recommended for routine lactation suppression or for the relief of painful symptoms and postpartum engorgement which can be adequately treated with non-pharmacological interventions (such as stable breast support, ice applications) and / or common analgesics.
Prolactin-dependent amenorrhea without galactorrhea.
Hyperprolactinemic infertility.
Dysfunctions of the menstrual cycle (short luteal phase).
Male hypogonadism prolactin-dependent.
Acromegaly: the first instance treatment of this condition is surgical or radiotherapy; Parlodel is a useful adjuvant to such treatments or, in particular cases, it can be used independently of them.
Parkinson's disease, idiopathic and arteriosclerotic: Parlodel is particularly useful in patients who show a decreasing therapeutic response to L-DOPA and in cases where the levodopatherapy is affected by the appearance of "on-off" phenomena. The combination with L-dopa achieves an increase in antiparkinsonian effects, which allows a reduced dosage of both drugs. Parlodel can be given alone in initial or mild cases of Parkinson's disease and can also be associated with anticholinergics and / or to other antiparkinsonian drugs.
04.2 Posology and method of administration
The drug should always be taken at mealtimes.
Galactorrhea and / or prolactin-dependent amenorrhea, hyperprolactinemic infertility:
half a tablet 3 times a day; if this dosage proves insufficient, gradually increase to 1 tablet 2-3 times a day, with meals. Continue the treatment until the complete disappearance of the mammary secretion and, if amenorrhea coexists, until the menstrual cycle returns to normal. If necessary, treatment can be continued for several menstrual cycles to avoid relapse.
Dysfunctions of the menstrual cycle (short luteal phase):
half a tablet 3 times a day, then gradually increasing to 1 tablet 2 times a day, with meals, until a normal luteal phase is restored.
Male hypogonadism : half a tablet 3 times a day, gradually increasing to 1 tablet 3 times a day, for 2-3 months.
Acromegaly : start with 1 tablet per day; gradually increase the dosage within 1-2 weeks, up to 4-8 tablets, in relation to individual demand, clinical response and tolerance. The daily dosage should be divided into 4 equal single doses.
Parkinson's disease : the antiparkinsonian effects can be obtained with low doses, from 10 to 15 mg per day. However, the therapeutically effective dose when Parlodel is given alone is usually higher. The maximum daily dose is 30 mg / day. If Parlodel is given in combination with L-dopa, with or without a dopa-decarboxylase inhibitor, lower doses may suffice. The recommended starting dose is 2.5 mg twice a day (with meals) for one week. Dosage increases should be small and regular, normally no more than 5 mg each
2-3 days at the initial stage of treatment; subsequently, further increases in dosage can be made gradually, of no more than 10 mg at a time, in relation to the therapeutic response and tolerance. Any reduction in L-DOPA dosage should be gradual, until the optimum effect is achieved; in some cases, L-DOPA can be totally suppressed.
04.3 Contraindications
Hypersensitivity to the active substance, to any of the excipients (see sections 2 and 6.1) or to other ergot alkaloids.
Bromocriptine is contraindicated in patients with uncontrolled hypertension, hypertensive disorders of pregnancy (including eclampsia, pre-eclampsia or pregnancy-induced hypertension), postpartum and postpartum hypertension.
Bromocriptine is contraindicated for use in the suppression of lactation, or other non-life threatening indications, in patients with a history of coronary artery disease or other serious cardiovascular conditions, or symptoms / history of severe psychiatric disorders.
For long-term treatment: evidence of cardiac valvulopathy determined on echocardiogram performed before treatment.
04.4 Special warnings and appropriate precautions for use
If women with conditions not related to hyperprolactinaemia are treated with Parlodel, the drug should be administered at the lowest effective dose, necessary to relieve symptoms, in order to avoid the possibility of lowering the prolactin levels below normal, with a consequent alteration. of the luteal function.
Such patients should have plasma prolactin and post-ovulatory progesterone determinations at regular intervals if treatment continues for more than 6 months.
Some reports of gastrointestinal bleeding and gastric ulcer have been reported. If this occurs, administration of Parlodel should be discontinued. Patients with a history of peptic ulcer or current peptic ulcer should preferably receive alternative treatment. If Parlodel is to be necessarily used in such patients, they should be advised to promptly report any gastrointestinal reactions.
Since, especially during the first days of treatment, hypotensive reactions may occasionally arise which lead to a reduction in alertness, particular attention must be paid when driving vehicles or using machinery. For the same reason, in outpatients it is advisable to check blood pressure values during the first days of treatment. If undesirable effects persist, the dose should be appropriately reduced.
Bromocriptine has been associated with somnolence and episodes of sudden sleep attacks, particularly in patients with Parkinson's disease.
Gambling, increased libido and hypersexuality have been reported in patients treated with dopamine agonists for Parkinson's disease including Parlodel.
Sudden sleep attacks have been reported very rarely during daily activity, in some cases without awareness and no warning signs. Patients taking bromocriptine should be informed of these events and advised to use caution while driving or operating machinery. . Patients who have experienced episodes of somnolence and / or an episode of sudden sleep should refrain from driving and operating machinery (see also section 4.7). In addition, a reduction in dosage or discontinuation of therapy may be considered.
Pleural and pericardial effusions, as well as pleural and pulmonary fibrosis and constrictive pericarditis have occasionally been reported among patients treated with bromocriptine, particularly long-term and at high doses. Patients with pleuropulmonary disorders of an undetermined nature should be carefully examined and 'discontinuation of Parlodel treatment should be considered.
Retroperitoneal fibrosis has been reported in some patients treated long-term and at high doses with Parlodel. In order to ensure the recognition of retroperitoneal fibrosis in an initial reversible stage, in this type of patients it is recommended to monitor the typical symptoms of this pathology (eg: back pain, edema of the lower limbs, functional alterations fibrotic alterations of the retroperitoneum .
In individuals with galactorrhea, prolactin-dependent amenorrhea, menstrual disturbances or acromegaly, treatment with Parlodel can eliminate pre-existing infertility. Therefore, women who could thus become fertile but who do not wish to become pregnant should adopt a method of mechanical contraception. Before starting treatment with Parlodel, the cause of infertility must be established.
Pregnancy should be avoided if a diagnosis of pituitary adenoma is made.
A marked enlargement of the sella turcica or a visual field defect requires surgical and / or radiotherapy treatment in the first instance. Parlodel is only indicated if these measures have failed. In the absence of pituitary adenoma and if the patient is anxious to conceive, Parlodel should be suspended as soon as possible after conception (early diagnosis of pregnancy with immunological test), since the knowledge on the possible effects of the drug on the evolution of pregnancy and on the fetus are still incomplete In cases of confirmed pregnancy, as a precautionary measure, the possible negative effects of a pituitary pathological event associated with pregnancy should be investigated regularly, for example by investigating the visual field.
Treatment in women should be under medical supervision including hormone dosage and gynecological examination. As good medical practice dictates, all women receiving Parlodel continuously for more than 6 months should have regular gynecological checks at annual intervals if the woman is pre-menopausal, every 6 months if she is in menopause (cervical cytology and, if possible, endometrial).
Use in postpartum women
In rare cases, serious adverse events, including hypertension, myocardial infarction, seizures, stroke or psychiatric disorders, have been reported in postpartum women treated with bromocriptine for lactation inhibition. In some patients the development of seizures, dizziness , syncope or stroke was preceded by severe headache and / or transient visual disturbances. Blood pressure should be carefully monitored, particularly during the first days of therapy. In case of hypertension, suspected chest pain, severe headache, progressive or incessant (with or without visual disturbances), or evidence of central nervous system toxicity, administration of bromocriptine should be discontinued and the patient promptly examined.
Particular caution is required in patients who have recently been treated or are on concomitant therapy with drugs that can alter blood pressure, for example vasoconstrictors such as sympathomimetics or ergot alkaloids, including ergometrine or methylergometrine.
Although there is no "conclusive evidence of a" interaction between Parlodel and these drugs, their concomitant use in the postnatal period is not recommended.
Use in parkinsonian patients
Caution is required when Parlodel is administered in high doses to parkinsonian patients with a history of psychotic disorders, severe cardiovascular disease, peptic ulcer or gastrointestinal bleeding.
Use in patients with impaired hepatic function
In patients with impaired hepatic function, the rate of elimination may be delayed and plasma levels may increase, requiring dosage adjustment.
Others
There is little evidence of Parlodel's efficacy in the treatment of premenstrual symptoms and benign breast disorders. The use of Parlodel in patients with these conditions is therefore not recommended.
Information about some of the ingredients of Parlodel
The tablets contain lactose therefore patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption should avoid taking this medicine.
Impulse control disorders
Patients should be monitored regularly for the development of impulse control disorders. Patients and carers should be aware that behavioral symptoms of impulse control disorder, including pathological gambling, increased libido, hypersexuality, compulsive shopping or overspending, bulimia and binge eating, can occur in treated patients. with dopamine agonists, including Parlodel Dose reduction / gradual withdrawal until discontinuation should be considered if such symptoms develop.
04.5 Interactions with other medicinal products and other forms of interaction
The possibility of interactions between bromocriptine and psychoactive or hypotensive drugs cannot be excluded.
Particular caution should be taken in patients being treated with ergot alkaloids or drugs that act on blood pressure in relation to a possible potentiating effect.
Bromocriptine is concomitantly a substrate and an inhibitor of cytochrome P3A4 (see section 5.2). Therefore, caution should be exercised when administering drugs that are strong inhibitors and / or substrates of this enzyme (azoline antifungals, HIV protease inhibitors).
Concomitant use of erythromycin, iosamycin, or other macrolide antibiotics may increase plasma levels of bromocriptine. In acromegalic patients, concomitant treatment with bromocriptine and octreotide resulted in increased plasma levels of bromocriptine. 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 can reduce its activity.
Tolerability to treatment can be reduced by the simultaneous intake of alcohol.
04.6 Pregnancy and lactation
Pregnancy
In patients wishing to conceive, Parlodel, like all other drugs, should be discontinued when pregnancy has been confirmed, unless there is a medical rationale for continuing therapy. No increased incidence of miscarriages has been observed following discontinuation of Parlodel therapy at this stage. Clinical experience indicates that Parlodel, administered during pregnancy, does not adversely affect its course and outcome.
Feeding time
As Parlodel inhibits lactation, it should not be taken by mothers who wish to breastfeed.
Women of childbearing age
Treatment with Parlodel can restore fertility. Women of childbearing age who do not wish to conceive should therefore be advised to practice a viable method of contraception.
04.7 Effects on ability to drive and use machines
Parlodel impairs the ability to drive or use machines. As, especially during the first days of treatment they can arise
occasionally hypotensive reactions that lead to a reduction in alertness, particular attention must be paid when driving vehicles or using machinery.
Patients treated with bromocriptine who experience episodes of drowsiness and / or sudden sleep attacks should be advised to refrain from driving or engaging in any activity in which impaired attention could expose themselves or others to the risk of serious harm or death. (eg using machines) until these recurrent episodes and somnolence have resolved (see 4.4).
04.8 Undesirable effects
Undesirable effects are listed according to frequency using the following convention: Very common (≥ 1/10); common (≥ 1/100,
Psychiatric disorders
Uncommon: Confusion, psychomotor agitation, hallucinations
Rare: Psychotic disorders, Insomnia
Very rare: Increased libido, hypersexuality and gambling addiction
Nervous system disorders
Common: Headache, lethargy, dizziness
Uncommon: Dyskinesia
Rare: Somnolence, Paresthesia
Very rare: Excessive sleepiness during the day, sudden sleep
Eye disorders
Rare: Visual disturbances, blurred vision
Ear and labyrinth disorders
Rare: Tinnitus
Cardiac disorders:
Rare: Pericardial effusion, constrictive pericarditis, tachycardia, bradycardia, arrhythmia
Very rare: Cardiac valvulopathy (including reflux) and related disorders (pleural and pericardial effusions)
Vascular pathologies
Uncommon: Hypotension, orthostatic hypotension (very rarely up to syncope)
Very rare: reversible paleness of the fingers and toes caused by cold (especially in patients with a history of Raynaud's phenomenon)
Respiratory, thoracic and mediastinal disorders
Common: Nasal congestion
Rare: Pleural effusions, pleural fibrosis, pleurisy, pulmonary fibrosis, dyspnoea
Gastrointestinal disorders
Common: Nausea, constipation, vomiting
Uncommon: Dry mouth
Rare: Diarrhea, abdominal pain, retroperitoneal fibrosis, gastrointestinal ulcer, gastrointestinal haemorrhage
Skin and subcutaneous tissue disorders
Uncommon: Allergic skin reactions, hair loss
Musculoskeletal and connective tissue disorders
Uncommon Leg cramps
General Disorders and Administration Site Site Conditions
Uncommon: Fatigability
Rare: Peripheral edema
Very rare: Neuroleptic Malignant Syndrome type syndrome due to abrupt discontinuation of Parlodel
Pathological gambling, increased libido, hypersexuality, compulsive shopping or overspending, bulimia and binge eating may occur in patients treated with dopamine agonists, including Parlodel (see section 4.4 Special warnings and precautions for use).
04.9 Overdose
Signs and symptoms
Symptoms of overdose may include nausea, vomiting, dizziness, hypotension, postural hypotension, tachycardia, lethargy, somnolence, lethargy and hallucinations.
Treatment
In the event of an overdose, administration of activated charcoal is recommended and, in the case of very recent oral intake, gastric lavage may be considered.
Treatment of acute intoxication is symptomatic. Metoclopramide can be used in the treatment of vomiting or hallucinations.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Prolactin inhibitors - Code
ATC: G02CB01.
Parlodel inhibits the secretion of the pre-pituitary hormone prolactin without affecting the normal levels of the other pituitary hormones. However Parlodel is able to reduce the elevated GH levels in patients with acromegaly: these effects are due to the stimulation of dopaminergic receptors.
In the puerperium, prolactin is needed to initiate and maintain lactation. In other conditions, increased prolactin secretion leads to pathological lactation (galactorrhea) and / or disorders of ovulation and menstruation. As a specific inhibitor of prolactin secretion, bromocriptine can be used to prevent or suppress physiological lactation , as well as to treat prolactin-induced disease states.
In "amenorrhea and / or in the absence of ovulation" (with or without galactorrhea) Parlodel can be used to restore menstruation and ovulation.
Specific measures for the suppression of lactation, such as the restriction of fluid administration, are not necessary during therapy with bromocriptine. Furthermore, Parlodel does not disturb the puerperal involution of the uterus and does not increase the risk of thromboembolism.
Bromocriptine has been found to stop the growth or reduce the mass of prolactin-dependent pituitary adenoma (prolactinoma).
Prolactin can also play a role in the pathogenesis of various cases of male hypogonadism: with Parlodel, a restoration of normal gonadal function and sexual potency is obtained by regulating the prolactin rate.
In acromegalic patients, in addition to reducing plasma levels of growth hormone (GH) and prolactin, Parlodel has a beneficial effect on the clinical picture and on glucose tolerance.
Bromocriptine improves clinical symptoms of polycystic ovarian syndrome by restoring normal levels of LH secretion.
In patients with benign breast disease, bromocriptine reduces the mass and number of cysts and / or lumps in the breast and relieves the breast pain often associated with this condition so as to normalize the progesterone / estrogen imbalance at its base. At the same time, bromocriptine reduces prolactin secretion in patients with high levels.
Due to its dopaminergic activity, Parlodel in doses usually higher than those required in endocrinological indications, is effective in the treatment of Parkinson's disease, characterized by a specific nigrostriatal dopamine deficiency. Under these conditions, the stimulation of dopamine receptors can restore the neurochemical balance in the striatum.
Parlodel improves clinical symptoms related to tremors, rigidity, bradykinesia and other parkinsonian symptoms in all phases of the disease. Therapeutic efficacy usually lasts for several years (in this regard, good results have been reported in patients treated for up to 8 years). Parlodel can be administered alone or - in the early as well as advanced stages of the disease - in combination with other antiparkinsonian drugs. The combination with levodopa produces an increase of the antiparkinsonian effects often making it possible to reduce the dosage of levodopa. Parlodel is particularly beneficial to patients on levodopa treatment for whom the therapeutic response is progressively reducing or who show complications such as abnormal involuntary movements (choreo-athetoid dyskinesia and / or painful dystonia), end-of-dose deterioration or "on- off ".
Parlodel improves the depressive symptoms often observed in Parkinsonians. This is due to its inherent antidepressant properties as demonstrated in controlled studies in non-Parkinsonian patients with endogenous or psychogenic depression.
05.2 "Pharmacokinetic properties
Absorption
After oral administration, PARLODEL is well absorbed. In healthy volunteers the absorption half-life is 0.2-0.5 hours and plasma levels of bromocriptine peak within 1-3 hours. An oral dose of 5 mg of bromocriptine produces a Cmax of 0.465 ng / mL. Prolactin-lowering effects occur within 1-2 hours of intake, reach the maximum (eg reduction of plasma prolactin by more than 80%) within
5-10 hours and remain close to the maximum for 8-12 hours.
Biotransformation
Bromocriptine undergoes "extensive first pass biotransformation in the liver, mirrored by a complex profile of metabolites and the almost complete absence of unchanged drug in urine and faeces. It exhibits a high affinity for cytochrome P3A and hydroxylations to" proline ring of the cyclopeptide molecule represent the major metabolic pathway. Inhibitors and / or potent substrates of cytochrome P3A4 may therefore inhibit the clearance of bromocriptine and cause its levels to increase. Bromocriptine is also a potent cytochrome P3A4 inhibitor with a calculated IC50 value of 1.69 mcM. In any case, given the low therapeutic concentrations of free bromocriptine in patients, a significant alteration of the metabolism of a second drug whose clearance is mediated by cytochrome P3A4 is not to be expected.
Elimination
Elimination of the drug from plasma is biphasic with a terminal half-life of approximately 15 hours (range 8-20 hours). Elimination of unchanged drug and its metabolites occurs almost completely through the liver, with only 6% eliminated through the kidney.
Plasma protein binding is approximately 96%.
Special patients
In patients with impaired hepatic function, the rate of elimination may be delayed and plasma levels may increase, requiring dosage adjustment.
05.3 Preclinical safety data
Acute toxicity
Acute toxicity studies using micronized bromocriptine revealed oral LD50 values equal to 2620 mg / kg in mice, greater than 1000 mg / kg in rabbits and greater than 2000 mg / kg in rats. The LD 50 values after i.v. were: mouse 190 mg / kg, rat 72 mg / kg and rabbit 12.5 mg / kg. Signs of toxicity were motor arousal, sometimes cramps, dyspnea and coma. High sensitivity in rabbits is characteristic of ergot derivatives in general.
Mutagenesis
Bromocriptine was found to have no potential genotoxic activity in studies on mutagenic effects in Salmonella typhimurium with and without metabolic activation, of clastogenic potential in the bone marrow in vitro (micronucleus test in mice, metaphasic chromosome tests in Chinese hamster).
Carcinogenesis
In a 100-week study in rats, bromocriptine was administered in feed at doses of 1.8, 9.9, or 44.5 mg / kg per day, equivalent to 25-100 times the human therapeutic dose for human inhibition of prolactin. Treatment caused a dose-dependent decrease in the incidence of tumors in all treated groups. This was reflected in a general decrease in the incidence of breast tumors in females and adrenal gland tumors in males. Both effects were probably related to the inhibitory action of prolactin by bromocriptine. In contrast, bromocriptine at medium high doses increased the incidence of uterine tumors. In a one-year study in the rat it was found that the effects on the uterus are the result of a prolonged estrogenic effect caused by the effect of inhibition of prolactin given by bromocriptine, particularly accentuated in the hypofunctioning endocrine system of elderly female rats. In the same study, in fact, it was shown that bromocriptine had inhibited the increase in plasma progesterone levels, associated with a state of pseudo-pregnancy, normally found in elderly female rats; estradiol levels were unchanged. after 53 weeks, there were no unexpected hyperplastic and metaplastic uterine lesions, which could progress to neoplasms when the duration of treatment was prolonged up to 100 weeks.
This finding is not relevant for women given the fundamental differences in the aging process of reproductive functions. In elderly female rats, unlike women, the ovarian response was maintained, both in support of pseudo-pregnancy on continuous prolactin stimulation, if hyperprolactinemia was suppressed by bromocriptine, and in support of estrogen dominance resulting in squamous metaplasia. of the genital tract. There is no evidence that these rat-specific pharmacodynamic effects are of any clinical significance in humans.
The loss of the direct stimulating effect on the uterus by bromocriptine was further highlighted in a 104-week study in ovariectomized female rats. A dose of 10 mg / kg per day administered in the feed did not induce changes in uterine or pre-neoplastic tumors. The absence of carcinogenic potential was confirmed in mice receiving bromocriptine in feed at doses up to 50 mg / kg per day. This revealed no difference in the incidence of any type of tumor between the treated animals and the control group.
Reproductive toxicity
No embryotoxic or teratogenic potential of bromocriptine was detected in rats, rabbits or monkeys.
In male animals, bromocriptine produced no effects on germ cells, fertility and offspring development. In female animals, fertility, prenatal development and offspring were not adversely affected after oral treatment with bromocriptine.
A high dose of 30 mg / kg administered to rats during the last period of pregnancy until delivery reduced the survival and weight gain of the newborns. The latter has been attributed to reduced lactation as a result of the inhibition of prolactin by bromocriptine. On the other hand, the postnatal development of F1 animals was impaired regardless of administration during the early or late stages of pregnancy. When administered to female stumptailed monkeys for one or more cycles and for consecutive pregnancies, doses of 0 , 15 mg / kg of bromocriptine twice daily had no effect on fertility or fetal development of the newborn.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Colloidal anhydrous silica, magnesium stearate, maleic acid, sodium edetate (dihydrate), corn starch, lactose.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
Store the product at a temperature not exceeding 25 ° C and protected from light.
06.5 Nature of the immediate packaging and contents of the package
Opaque PVC / PVDC / ALU blister. Box containing 30 tablets.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
Meda Pharma S.p.A., Viale Brenta 18, 20139 Milan
08.0 MARKETING AUTHORIZATION NUMBER
A.I.C. n. 023781014
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
27.11.1978/01.06.2005
