Drugs List

Therapeutic Indications

Uses

Hyperprolactinaemia
Lactation - inhibition of
Lactation - suppression of

Inhibition of lactation.

Suppression of established lactation.

Treatment of symptoms associated with hyperprolactinaemia, including amenorrhoea, oligomenorrhoea, anovulation and galactorrhoea. It is indicated in patients with prolactin-secreting pituitary adenomas (micro- and macroprolactinomas), idiopathic hyperprolactinaemia, or empty sella syndrome with associated hyperprolactinaemia.

Contraindications

Children under 16 years
History of fibrotic disorder
History of puerperal psychosis
Acute porphyria
Breastfeeding
Cardiac valvulopathy
Eclampsia
Galactosaemia
History of pericardial disorder
History of pulmonary fibrosis
Pre-eclampsia
Pregnancy
Pregnancy-induced hypertension
Retroperitoneal fibrosis
Uncontrolled hypertension

Precautions and Warnings

Cardiovascular disorder
Gastrointestinal haemorrhage
Glucose-galactose malabsorption syndrome
History of psychiatric disorder
Lactose intolerance
Peptic ulcer
Raynaud's syndrome
Renal impairment
Severe hepatic impairment

Advise ability to drive/operate machinery may be affected by side effects
Advise patient that sudden onset sleep episodes may affect ability to drive
In pituitary tumours, treat the underlying condition
Contains lactose
Baseline assessment of inflammatory markers/ESR advised
Baseline assessment of lung function advised
Consider chest x-ray prior to initiating therapy
Evaluate pituitary function before initiating long term therapy
Evaluate renal function before and during treatment
Exclude pregnancy prior to initiation of treatment
Perform echocardiography before commencing therapy
Discontinue if signs of gastro-intestinal bleeding occur
Ensure negative monthly pregnancy tests throughout treatment
Monitor for signs of fibrotic changes - discontinue if they occur
Monitor for signs of pulmonary toxicity on long term therapy
Monitor for signs of retroperitoneal fibrosis - discontinue if they occur
Monitor patients for impulse control disorders
Monitor patients for signs and symptoms of cardiac failure
Monitor serum prolactin during long-term use
Patient should have regular physical and gynaecological examinations
Perform ECHO after 3-6 months of starting drug, then every 6-12 months
Pregnancy:Monitor blood pressure in 1st days of treatment in the puerperium
Advise patient that postural hypotension may occur
Dopamine agonists have been associated with pathological gambling
Patient should be made aware of possible adverse effects on mood/behaviour
Discontinue if valvular regurgitation, restriction or thickening occurs
Pregnancy confirmed: Discontinue this medication
Reduce dose or discontinue if sudden onset of sleep during daily activities
Female: Contraception required during and for 1 month after treatment
Breastfeeding: Do not breastfeed if lactation suppression fails

Hyperprolactinaemic disorders

Before treatment
All patients must undergo a cardiovascular evaluation, including echocardiogram to assess the potential presence of asymptomatic valvular disease. Also perform baseline investigations of erythrocyte sedimentation rate or other inflammatory markers, lung function/chest X-ray, serum creatinine and renal function prior to initiation of therapy. If fibrotic valvular disease is detected, the patient should not be treated with cabergoline.

Patients with hyperprolactinaemia should undergo a complete pituitary evaluation to exclude patients with pituitary tumours before commencing treatment.

During Treatment
Fibrotic and serosal inflammatory disorders have occurred after prolonged use with ergot-derivatives such as cabergoline. Valvulopathy has been associated with cumulative doses, therefore patients should be treated with the lowest effective dose.

During long-term treatment, monitor for fibrotic disorders to prevent progressive fibrosis. The following symptoms should be monitored: dyspnoea, shortness of breath, persistent cough or chest pain; renal insufficiency or ureteral/abdominal vascular obstruction, lower limb oedema, abdominal masses or tenderness that may indicated retroperitoneal fibrosis; cases of valvular and pericardial fibrosis that may manifest as cardiac failure. Cabergoline should be discontinued if an ECHO reveals new or worsened valvular regurgitation, valvular restriction or valve leaflet thickening.

Clinical diagnostic monitoring for development of valvular disease or fibrotic disorders, is essential. Following treatment initiation, the first echocardiogram must occur within 3-6 months; thereafter the frequency of ECHO monitoring should be determined by appropriate individual clinical assessment, but must occur at least every 6-12 months.

Pathological gambling, increased libido, hypersexuality, compulsive spending, binge eating and other symptoms of impulse control disorder have been reported in patients treated with cabergoline. A reduction in dose or termination of therapy maybe considered.

Monitor women who become pregnant to detect sign of pituitary enlargement as pre-existing tumours may expand during gestation.

Pregnancy and Lactation

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Limited data regarding the use of cabergoline during human pregnancy at the lower doses used for hyperprolactinaemia gave no indication of an increased risk of birth defects in over 350 pregnancies that occurred during treatment (Schaefer, 2007). Manufacturers also reports data from 256 pregnancies, 17 pregnancies showed incidence of abortion and congenital abnormality. Musculoskeletal malformations were the most common neonatal abnormality, followed by cardio-pulmonary abnormalities.

If pregnancy is confirmed during therapy, then cabergoline should be discontinued to minimise foetal exposure. However, Briggs (2011) states that there is no evidence that exposure to cabergoline during pregnancy is harmful. Schaefer (2007) concludes that continuing treatment is not grounds for termination or invasive diagnostic procedure.

Cabergoline crosses the placenta in rats, although it is unknown whether this is also true for humans. Animal studies have shown no embryo or foetal toxicity (Briggs, 2011)

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Cabergoline suppresses lactation through its inhibition of prolactin release from the anterior pituitary gland. Therefore, it is not recommended for any woman wishing to breastfeed.

It is not known whether cabergoline is excreted in human breast milk although in rats, cabergoline and/or its metabolites have been present in milk. The manufacturer advises that in cases of failed inhibition or suppression of lactation, breastfeeding should not take place as the risk to humans is unknown. Schaefer (2007), however, concludes that as long as milk is being produced, breastfeeding may continue, even when cabergoline is being given. Hale (2010) also agrees that in cases where lactation is retained, breastfeeding may occur providing the infant is monitored for ergot side effects.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Abnormal fibrotic reactions
Abnormal liver function tests
Abnormal vision
Aggression
Allergic skin reactions
Alopecia
Angina
Asthenia
Binge eating
Breast pain
Cardiac valvulopathy
Chest pain
Compulsive disorders
Confusion
Constipation
Cramp
Creatine phosphokinase increased
Decrease in blood pressure
Decrease in haemoglobin
Delusions
Depression
Dizziness
Dyskinesia
Dyspepsia
Dyspnoea
Epigastric pain
Epistaxis
Erythromelalgia
Facial flushing
Fainting
Fatigue
Gastritis
Hallucinations
Headache
Hemianopia
Hepatic impairment
Hot flushes
Hypersensitivity reactions
Hypersexuality
Hypotension
Increased libido
Leg cramps
Muscle weakness
Nausea
Oedema
Orthostatic hypotension
Palpitations
Paraesthesia
Pathological gambling
Pericardial effusion
Pericarditis
Peripheral oedema
Pleural effusion
Pleuritis
Pruritus
Pulmonary fibrosis
Rash
Respiratory disorders
Respiratory failure
Retroperitoneal fibrosis
Sleep disturbances
Somnolence
Sudden sleep onset episodes
Syncope
Vasospasm
Vertigo
Vomiting

Presentation

Tablets containing 500 micrograms of cabergoline

Drugs List

Therapeutic Indications

Uses

Hyperprolactinaemia
Lactation - inhibition of
Lactation - suppression of

Inhibition of lactation.

Suppression of established lactation.

Treatment of symptoms associated with hyperprolactinaemia, including amenorrhoea, oligomenorrhoea, anovulation and galactorrhoea. It is indicated in patients with prolactin-secreting pituitary adenomas (micro- and macroprolactinomas), idiopathic hyperprolactinaemia, or empty sella syndrome with associated hyperprolactinaemia.

Dosage

The drug should only be prescribed by a specialist.

Adults

Patients with Renal Impairment

Patients with Hepatic Impairment

Contraindications

Children under 16 years
History of fibrotic disorder
History of puerperal psychosis
Acute porphyria
Breastfeeding
Cardiac valvulopathy
Eclampsia
Galactosaemia
History of pericardial disorder
History of pulmonary fibrosis
Pre-eclampsia
Pregnancy
Pregnancy-induced hypertension
Retroperitoneal fibrosis
Uncontrolled hypertension

Precautions and Warnings

Cardiovascular disorder
Gastrointestinal haemorrhage
Glucose-galactose malabsorption syndrome
History of psychiatric disorder
Lactose intolerance
Peptic ulcer
Raynaud's syndrome
Renal impairment
Severe hepatic impairment

Advise ability to drive/operate machinery may be affected by side effects
Advise patient that sudden onset sleep episodes may affect ability to drive
In pituitary tumours, treat the underlying condition
Contains lactose
Baseline assessment of inflammatory markers/ESR advised
Baseline assessment of lung function advised
Consider chest x-ray prior to initiating therapy
Evaluate pituitary function before initiating long term therapy
Evaluate renal function before and during treatment
Exclude pregnancy prior to initiation of treatment
Perform echocardiography before commencing therapy
Discontinue if signs of gastro-intestinal bleeding occur
Ensure negative monthly pregnancy tests throughout treatment
Monitor for signs of fibrotic changes - discontinue if they occur
Monitor for signs of pulmonary toxicity on long term therapy
Monitor for signs of retroperitoneal fibrosis - discontinue if they occur
Monitor patients for impulse control disorders
Monitor patients for signs and symptoms of cardiac failure
Monitor serum prolactin during long-term use
Patient should have regular physical and gynaecological examinations
Perform ECHO after 3-6 months of starting drug, then every 6-12 months
Pregnancy:Monitor blood pressure in 1st days of treatment in the puerperium
Advise patient that postural hypotension may occur
Dopamine agonists have been associated with pathological gambling
Patient should be made aware of possible adverse effects on mood/behaviour
Discontinue if valvular regurgitation, restriction or thickening occurs
Pregnancy confirmed: Discontinue this medication
Reduce dose or discontinue if sudden onset of sleep during daily activities
Female: Contraception required during and for 1 month after treatment
Breastfeeding: Do not breastfeed if lactation suppression fails

Hyperprolactinaemic disorders

Before treatment
All patients must undergo a cardiovascular evaluation, including echocardiogram to assess the potential presence of asymptomatic valvular disease. Also perform baseline investigations of erythrocyte sedimentation rate or other inflammatory markers, lung function/chest X-ray, serum creatinine and renal function prior to initiation of therapy. If fibrotic valvular disease is detected, the patient should not be treated with cabergoline.

Patients with hyperprolactinaemia should undergo a complete pituitary evaluation to exclude patients with pituitary tumours before commencing treatment.

During Treatment
Fibrotic and serosal inflammatory disorders have occurred after prolonged use with ergot-derivatives such as cabergoline. Valvulopathy has been associated with cumulative doses, therefore patients should be treated with the lowest effective dose.

During long-term treatment, monitor for fibrotic disorders to prevent progressive fibrosis. The following symptoms should be monitored: dyspnoea, shortness of breath, persistent cough or chest pain; renal insufficiency or ureteral/abdominal vascular obstruction, lower limb oedema, abdominal masses or tenderness that may indicated retroperitoneal fibrosis; cases of valvular and pericardial fibrosis that may manifest as cardiac failure. Cabergoline should be discontinued if an ECHO reveals new or worsened valvular regurgitation, valvular restriction or valve leaflet thickening.

Clinical diagnostic monitoring for development of valvular disease or fibrotic disorders, is essential. Following treatment initiation, the first echocardiogram must occur within 3-6 months; thereafter the frequency of ECHO monitoring should be determined by appropriate individual clinical assessment, but must occur at least every 6-12 months.

Pathological gambling, increased libido, hypersexuality, compulsive spending, binge eating and other symptoms of impulse control disorder have been reported in patients treated with cabergoline. A reduction in dose or termination of therapy maybe considered.

Monitor women who become pregnant to detect sign of pituitary enlargement as pre-existing tumours may expand during gestation.

Pregnancy and Lactation

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Limited data regarding the use of cabergoline during human pregnancy at the lower doses used for hyperprolactinaemia gave no indication of an increased risk of birth defects in over 350 pregnancies that occurred during treatment (Schaefer, 2007). Manufacturers also reports data from 256 pregnancies, 17 pregnancies showed incidence of abortion and congenital abnormality. Musculoskeletal malformations were the most common neonatal abnormality, followed by cardio-pulmonary abnormalities.

If pregnancy is confirmed during therapy, then cabergoline should be discontinued to minimise foetal exposure. However, Briggs (2011) states that there is no evidence that exposure to cabergoline during pregnancy is harmful. Schaefer (2007) concludes that continuing treatment is not grounds for termination or invasive diagnostic procedure.

Cabergoline crosses the placenta in rats, although it is unknown whether this is also true for humans. Animal studies have shown no embryo or foetal toxicity (Briggs, 2011)

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Cabergoline suppresses lactation through its inhibition of prolactin release from the anterior pituitary gland. Therefore, it is not recommended for any woman wishing to breastfeed.

It is not known whether cabergoline is excreted in human breast milk although in rats, cabergoline and/or its metabolites have been present in milk. The manufacturer advises that in cases of failed inhibition or suppression of lactation, breastfeeding should not take place as the risk to humans is unknown. Schaefer (2007), however, concludes that as long as milk is being produced, breastfeeding may continue, even when cabergoline is being given. Hale (2010) also agrees that in cases where lactation is retained, breastfeeding may occur providing the infant is monitored for ergot side effects.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Counselling

Advise patients to take the tablets with or after food.

Advise patients that excessive daytime sleepiness or sudden onset of sleep and hypotensive reactions may occur and that they should exercise caution when driving or operating machinery. Patients who have been affected by excessive daytime sleepiness or sudden onset of sleep should be advised that they should not drive or operate machinery until the effects have stopped recurring.

Advise women to use non-hormonal methods of contraception during treatment and for 1 month thereafter.

Women who wish to become pregnant should conceive at least 1 month after cessation of treatment.

Women who do not wish to become pregnant should use non-hormonal methods of contraception during treatment and, following treatment, until the recurrence of anovulation (due to hyperprolactinaemic disorder).

Side Effects

Abdominal pain
Abnormal fibrotic reactions
Abnormal liver function tests
Abnormal vision
Aggression
Allergic skin reactions
Alopecia
Angina
Asthenia
Binge eating
Breast pain
Cardiac valvulopathy
Chest pain
Compulsive disorders
Confusion
Constipation
Cramp
Creatine phosphokinase increased
Decrease in blood pressure
Decrease in haemoglobin
Delusions
Depression
Dizziness
Dyskinesia
Dyspepsia
Dyspnoea
Epigastric pain
Epistaxis
Erythromelalgia
Facial flushing
Fainting
Fatigue
Gastritis
Hallucinations
Headache
Hemianopia
Hepatic impairment
Hot flushes
Hypersensitivity reactions
Hypersexuality
Hypotension
Increased libido
Leg cramps
Muscle weakness
Nausea
Oedema
Orthostatic hypotension
Palpitations
Paraesthesia
Pathological gambling
Pericardial effusion
Pericarditis
Peripheral oedema
Pleural effusion
Pleuritis
Pruritus
Pulmonary fibrosis
Rash
Respiratory disorders
Respiratory failure
Retroperitoneal fibrosis
Sleep disturbances
Somnolence
Sudden sleep onset episodes
Syncope
Vasospasm
Vertigo
Vomiting

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: July 2013

Reference Sources

British National Formulary, 65nd Edition (March - September 2013) Pharmaceutical Press, London.

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Dostinex tablets. Pfizer Ltd. Revised January 2013.

Summary of Product Characteristics: Cabaser 1mg tablets. Pfizer Ltd. Revised January 2013.

Summary of Product Characteristics: Cabaser 2mg tablets. Pfizer Ltd. Revised January 2013.

The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Cabergoline Last revised: January 24, 2013
Last accessed: July 16, 2013

Drug Safety Update: Volume 2 issue 3 October 2008.
https://www.mhra.gov.uk/Publications/Safetyguidance/DrugSafetyUpdate/CON028267
Last accessed: July 16, 2013

The drug database for acute porphyria
https://www.drugs-porphyria.org/monograph.php?id=2139
Cabergoline Last revised October 1, 2010
Last accessed: July 16, 2013