Generic Dostinex, Cabergoline Tablet Patient Information Sheet
For the use of a Gynaecologist or a Hospital or a Laboratory only.
Prescribing Information
Cabergoline Tablets
CABGOLIN
Dosage Form:
Tablet
Composition:
Each uncoated tablet of Cabgolin 0.25 contains:
Cabergoline 0.25 mg
Each uncoated tablet of Cabgolin 0.5 contains:
Cabergoline 0.5 mg
Clinical Pharmacology:
Cabergoline is a long-acting dopamine receptor agonist with a high affinity tor D2, receptors. Receptor-binding studies indicate thai cabergoline has low affinity fordopamine D1„ (alpha)1, and (alpha)2,-adrenergic and 5-HT, and 5-HT2, serotonin receptors.
Mechanism ot Action
The secretion of prolactin by the anterior pituitary is mainly under hypothalamic inhibitory control, likely exerted through release of dopamine by tuberoinfundibular neurons. Results of in vitro studies demonstrate that cabergoline exerts a direct inhibitory effect on the secretion of prolactin by pituitary lactotrophs. Cabergoline decreased serum prolactin levels as demonstrated in reserpinised rats.
Pharmacokinetics:
Following single oral doses of 0.5 mg to 1.5 mg given to 12 healthy adult volunteers, mean peak plasma levels of 30 to 70 picograms (pg)/mL_ of cabergoline were observed within 2 to 3 hours. Over the 0.5 to 7 mg dose range, cabergoline plasma levels appeared to be dose-proportional in 12 healthy adult volunteers and nine adult parkinsonian patients A repeat-dose study in 12 healthy volunteers suggests that steady-state levels following a once-weekly dosing schedule are expected to be twofold to threefold higher than after a single dose. The absolute bioavailability of cabergoline is unknown. A significant fraction of the administered dose undergoes a first-pass effect. The elimination half-life of cabergoline estimated from urinary data of 12 healthy subjects ranged between 63 to 69 hours The prolonged prolactin-lowering effect ot cabergoline may be related to its slow elimination and long half-life.
The drug is extensively distributed throughout the body. Cabergoline is moderately bound (40% to 42%) to plasma proteins in a concentration-independent manner. Concomitant dosing of highly protein-bound drugs is unlikely to affect its disposition.
In both animals and humans, cabergoline is extensively metabolized, predominately via hydrolysis of the acylurea bond or the urea moiety. Cytochrome P-450 mediated metabolism appears to be minimal. Cabergoline does not cause enzyme induction and/or inhibition in the rat. Hydrolysis ol the acylurea or urea moiety abolishes the prolactin-lowering effect of cabergoline and major metabolites identified thus far do not contribute to the therapeutic effect.
After oral dosing of radioactive cabergoline to live healthy volunteers, approximately 22% and 60% of the dose was excreted within 20 days in the urine and faeces, respectively. Less than 4% of the dose was excreted unchanged in the urine. Nonrenal and renal clearances for cabergoline are about 3.2 L/min and 0.08 L/min, respectively. Urinary excretion in hyperprolactinemic patients was similar.
The pharmacokinetics of cabergoline was not altered in patients with mild to moderate to severe renal insufficiency, however, patients with severe hepatic insufficiency show a marked increase in the mean Cmax and AUC and thus require cauton.
Indications:
• Hyperprolactinemia.
• Inhibition and suppression of lactation.
Contra-indications:
• Uncontrolled hypertension or known hypersensitivity to ergot derivatives.
• Toxaemia of pregnancy.
• Women with a history of puerperal psychosis.
Warnings and Precautions:
Cabergoline in general should not be used in patients with pregnancy-induced hypertension, for example, preeclampsia and eclampsia, unless the potential benefit is judged to outweigh the possible risk.
Caution is advised when administering cabergoline to patients with hepatic impairment since it is extensively metabolised by the liver.
Cabergoline should be given with caution to patients with cardiovascular disease. Raynaud's syndrome, renal insufficiency, peptic ulcer, Gl bleeding or in those with a history of serious psychiatric disorder.
Symptomatic hypotension can occur and care should be exercised when administering cabergoline with other drugs known to lower blood pressure.
Although a slight fall in blood pressure is generally noted during the puerperium independent of drug therapy, periodic monitoring of the blood pressure (in puerperium or otherwise) during the first few doses of cabergoline administration is recommended.
Since hyperprolactinemia with amenorrhoea/galactorrhoea and infertility may be associated with pituitary tumours, a complete evaluation of the pituitary is indicated before starting treatment with cabergoline. It restores ovulation and fertility in women with hyperprolactinemic hypogonadism. Since pregnancy might occur prior to reinitiation of menses, a pregnancy test is recommended atleast every four weeks during the amenorrhoeic period and once menses are reinitiated; every time a menstrual period is delayed by more than three days. Women not seeking pregnancy should use non hormonal method of contraception during treatment and after cabergoline withdrawal until recurrence of anovulation. Should pregnancy occur during treatment, cabergoline should be discontinued. As a precautionary measure women who become pregnant should be monitored to detect signs of pituitary expansion since expansion of pre-existing pituitary tumors may occur during gestation.
While there is no information on the excretion ot cabergoline in maternal milk in the humans; puerperal women should be advised not to breast feed the child (in case of failed lactation inhibition/suppression by cabergoline).
Regular gyaenocological assessment, including cervical and endometrial cytology is recommended lor patients using cabergoline tor long periods of time.
Pregnancy & Lactation
Cabergoline is reported to cross the placental barrier in rats but it is unknown whether this also occurs in humans. Animal studies have not demonstrated any teratogenic effect. The use of cabergoline does not appear to be associated with an increased risk ot abortion, premature delivery, multiple pregnancy or congenital abnormalities.
Because the clinical experience is limited and the drug has a long half-life, it is recommended that women seeking pregnancy should discontinue cabergoline one month before intended conception as a precautionary measure. This will prevent foetal exposure to the drug and will not interfere with the possibility ot conception since ovulatory cycles persist in some cases for six months after withdrawal. If conception occurs during therapy, treatment should be discontinued immediately to limit foetal exposure to the drug. Before cabergoline administration, pregnancy should be excluded and after treatment, pregnancy should be prevented for atleast one month.
The prolactin-lowering action of cabergoline suggests that it will interfere with lactation and no information is available on the excretion of the drug in maternal milk. Therefore, cabergoline should not be given to women postpartum who are breastfeeding or who intend to breast feed.
Drug Interactions:
Cabergoline should not be administered concurrently with D2-antagonists such as phenothiazines, butyrophenones thioxanthines or metoclopramide.
Just like the other ergot alkaloids, cabergoline should not be used with macrolide antibiotics (e.g., erythromycin) since the systemic bioavailability and adverse effects could increase.
Although there is no conclusive evidence of an interaction between other ergot alkaloids and cabergoline; the concomitant use of these medications especially during long term treatment is not recommended.
The effects of alcohol on overall tolerability of cabergoline are unknown.
Side effects:
Most adverse effects reported with cabergoline were mild to moderate in severity. The most commonly reported adverse effects were: nausea, constipation, abdominal pain, dyspepsia, vomiting, headache, dizziness, paraesthesia, vertigo, asthenia, fatigue, hot flushes, somnolence, depression, nervousness, postural hypotension, breast pain, dysmenorrhoea. abnormal vision. Rarely palpitations, epistaxis, asymptomatic decrease in blood pressure, transient hemianopsia, epigastric pain, digital vasospasm and leg cramps have been reported.
The other adverse effects reported were dry mouth, diarrhoea, flatulence, throat irritation, toothache, syncope, influenza like symptoms, malaise, periorbital oedema, peripheral oedema, anorexia, anxiety, insomnia, impaired concentration, dependent oedema, acne, pruritis. pain, arthralgia, rhinitis, weight loss, weight gain and increased libido.
Overdosage:
Overdosage might be expected to produce symptoms due to overstimulation of dopamine receptors. These might include nausea, vomiting, gastric complaints, nasal congestion, hypotension, confusion/psychosis and hallucinations. In case of overdose, general measures should be taken to remove any unabsorbed drug and supportive therapy to maintain blood pressure and other vital signs may be instituted. Also if need be, dopamine antagonist drugs may be administered.
Dosage and Administration:
Cabergoline should preferably be taken with food for all therapeutic indications.
Hyperprolactinemia:
Cabergoline is indicated tor the treatment oft hyperprolactinemia that may be associated with amenorrhoea, oligomenorrhoea, anovulation and galactorrhoea. It is also indicated in patients with prolactin secreting pituitary adenomas (micro and macro prolactinomas), idiopathic hyperprolactinemia or empty sella syndrome with associated hyperprolactinemia.
The recommended dosage for initiation of therapy is 0.5 mg per week given as a single dose or in two divided doses i.e., 0.25 mg twice a week (e.g., on Monday and Thursday) The weekly dose should be increased gradually, preferably by adding 0.5 mg per week at monthly intervals until an optimal therapeutic response is achieved. The therapeutic dosage is usually 1 mg per week and ranges from 0.25 mg to 2 mg per week. Doses of up to 4.5 mg per week have been used in hyperprolactinemic patients.
The weekly dose may be given as a single administration or in two or more divided doses per week according to the patients tolerability. Division of the weekly dose into multiple administrations is especially advised when doses higher than 1 mg per week are to be given, since the tolerability of doses greater than 1 mg as a single weekly dose has been evaluated only in a few number of patients.
Monitoring of serum prolactin levels at monthly interval is recommended till normoprolactinemia or maximum therapeutic response is achieved. This helps to determine the lowest dose that produces maximum therapeutic response.
If the patient does not respond adequately and no additional benefit is observed with higher doses, the lowest dose that achieved maximal response should be used and other therapeutic approaches considered.
After a normal serum prolactin level has been maintained for 6 months, cabergoline may be discontinued, with periodic monitonng of the serum prolactin level to determine whether or when treatment with cabergoline should be reinstituted. The durability of efficacy beyond 24 months of therapy with cabergoline has not been established.
Inhibition/supression of physiological lactation:
Cabergoline is indicated for the inhibition of physiological lactation soon after delivery and for suppression of already established lactation. (1) It is indicated for use after parturition when the mother elects not to breast feed or when breastfeeding is contraindicated due to medical reasons related to the mother or the neonate. (2) After stillbirth or abortion.
For inhibition of lactation cabergoline should be administered dunng the first day postpartum. The recommended therapeutic dose is 1 mg given as a single dose.
For suppression of established lactation the recommended therapeutic dose regimen is 0 25 mg every 12 hours for two days (total dose of 1 mg). This dosage regimen has shown to be better tolerated than the single dose regimen in women electing to suppress lactation; having a lower incidence of adverse events, in particular, hypotensive symptoms.
Elderly: As a consequence of the indications for which cabergoline is proposed, the experience in elderly is very limited. But the available data do not indicate a special risk
Pediatric use. The safety and efficacy has not been established in subjects below the age of 16 years.
Incompatibilities:
None known.
Storage & Handling:
Store in a cool, dry place, protected from light. Keep out of reach of children.
Expiry Date:
Refer product label for expiry date. Do not use after expiry date.
Presentation:
Cabgolin 0.25/ Cabgolin 0.5 are available in strips of 2 tablets.
For further details, please write to:
sun pharmaceutical industries.
Acme Plaza. Andhen-Kurfa Road. Andheti (East). Mumbai-400 059.
|
