Cabergoline

Registered South African indications:

• Inhibition of lactation
• Hyperprolactinaemic disorders

Contraindications 

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to any ergot alkaloid
• History of pulmonary disorders
• History of pericardial disorders
• History of retroperitoneal fibrotic disorders  
• Toxaemia of pregnancy
• History of puerperal psychosis
• Cardiac valvulopathy determined by pre-treatment echocardiography (long-term treatment)
• Coadministration with antipsychotic agents

Cautions 

• Pregnancy
• Breastfeeding
• Renal impairment
• Severe hepatic impairment
• Pregnancy-induced hypertension, including preeclampsia or post-partum hypertension
• Severe cardiovascular disease
• Raynaud's syndrome
• Peptic ulcer
• Gastrointestinal bleeding
• History of mental disorders
• Parkinson's disease
• Fibrotic valvular disease (long-term treatment)
• Pre-existing pituitary tumours
• Prolonged usage of ergot derivatives with agonist activity at the serotonin 5HT receptor 2B
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: tab

Inhibition/ suppression of physiological lactation
- After parturition, when the mother elects not to breastfeed the infant or when breastfeeding is contraindicated due to medical reasons related to the mother or the new-born
- After stillbirth or abortion

• Oral (tab): 1mg, as a single dose

Administered on day one post-partum

Suppression of established lactation 

• Oral (tab): 0.25mg, 12hrly; Treatment duration: 2 days

This dosage regimen has been demonstrated to be better tolerated than the single dose regimen in women electing to suppress lactation having a lower incidence of adverse events, in particular of hypotensive symptoms

Hyperprolactinaemic disorders
- Including amenorrhoea, oligomenorrhoea, anovulation and galactorrhoea
- Prolactin-secreting pituitary adenomas (micro- and macroprolactinomas), idiopathic hyperprolactinaemia, or empty sella syndrome with associated hyperprolactinaemia

• Oral (tab): 0.5mg/week, in 1-2 divided doses; Titrate by 0.5mg/week at intervals of 1 month; Maintenance: 0.25-4.5mg/week, in 1-2 divided doses; Max: 3mg/24hrs

The weekly dose may be given as a single administration or divided into two or more doses per week according to patient tolerability

Division of the weekly dose into multiple administrations is advised when doses higher than 1mg per week are to be given since the tolerability of doses greater than 1mg taken as a single weekly dose has been evaluated only in a few patients

Patients should be evaluated during dose escalation to determine the lowest dosage that produces the therapeutic response

Monitoring of serum prolactin levels at monthly intervals is advised since, once the effective therapeutic dosage regimen has been reached, serum prolactin normalisation is usually observed within two to four weeks

After cabergoline withdrawal, recurrence of hyperprolactinaemia is usually observed. However, persistent suppression of prolactin levels has been observed for several months in some patients

It is recommended that cabergoline be preferably taken with meals

Not established for use in patients below 16 years

Pregnancy

• Caution
• There are no adequate and well-controlled studies from the use of cabergoline in pregnant women. Animal studies have not demonstrated teratogenic effects, but reduced fertility and embryo-toxicity were observed in association with pharmacodynamic activity. In a twelve year observational study on pregnancy outcomes following cabergoline therapy, information is available on 256 pregnancies. Seventeen of these 256 pregnancies (6.6%) eventuated in major congenital malformations or abortion
• Information is available on 23/258 infants who had a total of 27 neonatal abnormalities, both major and minor. Musculoskeletal malformations were the most common neonatal abnormality (10), followed by cardio-pulmonary abnormalities (5). There is no information on perinatal disorders or long-term development of infants exposed to intrauterine cabergoline. Based on recent published literature, the prevalence of major congenital malformations in the general population has been reported to be 6.9% or greater. Rates of congenital abnormality vary between different populations. It is not possible to accurately determine if there is an increased risk as no control group was included
• Cabergoline should only be used during pregnancy if clearly indicated and after an accurate benefit/ risk evaluation
• Due to the long half-life of the agent and limited data on in utero exposure, women planning to become pregnant should discontinue cabergoline one month before intended conception. If conception occurs during therapy, treatment should be discontinued as soon as pregnancy is confirmed to limit foetal exposure to the drug

Breastfeeding

• Caution; not recommended
• In rats, cabergoline and/or its metabolites are excreted in milk. No information is available on the excretion in breast milk in humans; however, mothers should be advised not to breastfeed in case of failed lactation inhibition/ suppression by cabergoline. Since it prevents lactation, cabergoline should not be administered to mothers with hyperprolactinemic disorders who wish to breastfeed their infants

Fertility

• In animal studies, reduced fertility was observed in association with pharmacodynamic activity. Cabergoline restores ovulation and fertility in women with hyperprolactinaemic hypogonadism

Renal Impairment

• Caution; no information available
  The safety and efficacy of cabergoline have not yet been established in patients with renal disease

Hepatic Impairment

• Mild to moderate (Child-Pugh Classes A & B): No dose adjustment recommended
• Severe (Child-Pugh Class C): Caution; dose adjustment recommended
  Suppression of established lactation: No dose adjustment is required; Use single dose protocol: 0.25mg once-off
  Hyperprolactinaemic disorders: 0.25mg, twice weekly; Maximum weekly dose: 0.5mg/week

Elderly

• No dose adjustment recommended
  Experience of use is limited in the elderly
  Start at lower end of dosage range

Porphyria Information

• Probably not porphyrinogenic (PNP)
  Nausea and vomiting, obstipation and dyspepsia are reported adverse effects of cabergoline that may potentially be porphyrinogenic if leading to a decrease in carbohydrate intake

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Dizziness
• Vertigo
• Confusion
• Somnolence
• Syncope
• Sudden sleep onset
• Tremor
• Depression
• Increased libido
• Aggression
• Delusions
• Hypersexuality
• Pathological gambling
• Compulsive spending or buying
• Binge and compulsive eating
• Psychotic disorder
• Hallucinations
• Paraesthesia
• Fainting
• Asthenia

Cardiovascular Disorders

• Valvulopathy, including regurgitation
• Pericarditis
• Pericardial effusion
• Palpitations
• Angina pectoris
• Hypotension (long-term treatment)
• Asymptomatic decreases in blood pressure (20mmHg systolic and 10mmHg diastolic)
• Postural hypotension  
• Digital vasospasm
• Oedema
• Peripheral oedema

Respiratory Disorders

• Dyspnoea
• Pleural effusion
• Fibrosis
• Epistaxis
• Pulmonary fibrosis
• Pleural fibrosis
• Respiratory failure
• Pleuritis
• Chest pain

Gastrointestinal Disorders

• Nausea and vomiting
• Dyspepsia
• Gastritis
• Gastrointestinal ulceration
• Abdominal pain
• Constipation
• Epigastric pain

Hepatobiliary Disorders

• Abnormal hepatic function tests

Genitourinary Disorders

• Breast pain

Musculoskeletal Disorders

• Leg cramps
• Increased blood creatinine phosphokinase

Skin and Subcutaneous Tissue Disorders

• Rash
• Alopecia
• Hot flushes

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reaction
• Decrease in haemoglobin values (amenorrhoeic women)

Sensory Disorders

• Visual impairment
• Transient hemianopsia

• Ergot alkaloids
• Dopamine antagonists
• Phenothiazines
• Butyrophenones
• Thioxanthenes
• Metoclopramide
• Macrolide antibiotics
• Erythromycin
• Agents known to lower blood pressure
• Antihypertensive agents
• Psychoactive medication

• Serum prolactin
• Blood pressure

None routine. Specific cases may require

• ECG
• Chest X-ray
• Erythrocyte sedimentation rate
• CT scan
• Lung function test
• Serum creatinine
• Pregnancy test

Additional observations

• Fibrotic disorders
• Cardiac auscultation
• Gynaecological assessment (cervical and endometrial cytology)

Cabergoline is a dopaminergic ergoline derivative endowed with a potent and long-lasting PRL-lowering activity. It acts by direct stimulation of the D-dopamine receptors on pituitary lactotrophs, thus inhibiting PRL secretion. In addition, cabergoline exerts a central dopaminergic effect via D receptor stimulation at oral doses higher than those effective in lowering serum PRL levels. The long lasting PRL-lowering effect of cabergoline is probably due to its long persistence in the target organ.

Tablet 0.5mg

• Arigoline (Actavis Pharma) (Discontinued: 06/12/2021)
• Dostinex (Pfizer) originator