Generic Name: Cabergoline
Brand Names: Various around the world
What is Cabergoline;
Cabergoline is a dopamine agonist medication primarily used to treat hyperprolactinemia, a condition characterised by elevated levels of prolactin in the blood. Cabergoline side effects will be extensively analysed later in the text. Some popular brand names containing cabergoline include Dostinex, Cabaser, Caberlin, and Bergolac. Cabergoline was first synthesized in 1981 by scientists at the Italian pharmaceutical company Farmitalia Carlo Erba. It was approved for medical use in the United States in 1996. In this article, we will analyze information from studies published in “Expert Opinion on Pharmacotherapy” by A Colao, G Lombardi, and L Annunziato, as well as “Clinical Pharmacokinetics” by P Del Dotto and U Bonuccelli.
The main purpose of the dopamine agonist medication cabergoline is to treat hyperprolactinemia, a disorder marked by high blood levels of prolactin. To increase effectiveness and reduce adverse effects, cabergoline was created as a substitute for bromocriptine, another dopamine agonist. Acromegaly, fibrosing dysplasia, and Parkinson’s disease have all been treated off-label with cabergoline. Numerous academic research and medical publications have thoroughly examined the pharmacological activity and therapeutic uses of cabergoline.
Chemical Structure and Mechanism of Action
Cabergoline is a semi-synthetic derivative of ergotamine with the molecular formula C26H37N5O2. Its chemical structure consists of an ergoline backbone substituted at position 8b with N-ethyl-N-methyl carbamide. According to Colao et al. (2000), this structural alteration improves cabergoline’s selectivity and binding affinity for dopamine D2 receptors, particularly in the pituitary.
The direct activation of dopamine D2 receptors in the pituitary gland’s lactotropic cells is the primary mode of action of cabergoline. Prolactin is not released when these receptors are activated, which lowers blood levels of the hormone. Because of its extended half-life and high receptor binding, cabergoline provides a longer duration of action that permits sparse dosage regimens (Del Dotto & Bonuccelli, 2003).
Cabeazoline activates postsynaptic dopamine D2 receptors in the brain’s basal ganglia in addition to its impact on the pituitary gland. Its improvement of the motor symptoms linked to dopaminergic insufficiency underlies its therapeutic benefits in Parkinson’s disease. Furthermore, a possible contributing factor to the unfavourable impact profile of cabergoline is its low affinity for serotonin 5-HT2B and 5-HT2C receptors (Colao et al., 2000).
Uses
Although cabergoline has several medical uses, treating hyperprolactinemia is the most common one. An endocrine condition called hyperprolactinemia is defined by high blood levels of prolactin. It can cause galactorrhea, infertility, monthly irregularities, and sexual dysfunction, among other symptoms. Many individuals get symptom relief and normal levels of prolactin production as a result of cabergoline’s efficient inhibition of pituitary gland secretion (Colao).
Cabergoline is used not just to treat hyperprolactinemia but also Parkinson’s disease. Cabergoline functions as a dopamine agonist, stimulating dopamine receptors in the brain to alleviate bradykinesia, stiffness, and tremors, which are motor symptoms of the condition. In the early stages of Parkinson’s disease, cabergoline can be taken alone; in the later stages, it can be used as supplementary therapy in conjunction with levodopa (Del Dotto & Bonuccelli, 2003).
Acromegaly is a rare endocrine condition that is treated with cabergoline due to excessive growth hormone production. Certain people with acromegaly may have a decrease in growth hormone and insulin-like growth factor-1 (IGF-1) levels when using cabergoline in conjunction with other therapies such somatostatin analogues or in patients with milder forms of the condition.
Furthermore, cabergoline has been studied as a possible therapy for fibrous dysplasia, a rare bone disorder where fibrous tissue replaces normal bone. Cabergoline has been demonstrated to lessen bone pain and enhance bone deterioration in certain cases of hyperprolactinemia associated with fibrotic dysplasia.
Despite having many therapeutic uses, cabergoline should only be taken sparingly and under a doctor’s supervision. It is important to consider each patient’s unique side effect profile and take appropriate precautions. The suitability of cabergoline therapy in a given clinical scenario must be determined by carefully weighing the advantages and disadvantages of the treatment.
Cabergoline Side Effects
Common Cabergoline Side Effects
Like any medications, cabergoline can have adverse effects, although most patients handle it well most of the time. The most typical cabergoline adverse effects are headache, tiredness, nausea, and indigestion. When therapy is continued, these often moderate and temporary adverse effects go away. Additionally, orthostatic hypotension—a sharp decrease in blood pressure upon standing—may transpire, especially during the onset of therapy or following a dosage increase (Colao et al., 2000).
Other typical side effects of cabergoline include malaise, weakness, and pains in the muscles, which are flu-like symptoms. Some individuals may also have peripheral oedema, or swelling in the extremities. Additionally documented are gastrointestinal disorders such dry mouth, constipation, and stomach discomfort. Usually, these adverse effects are tolerable and don’t necessitate stopping the medication.
Rare but Possible Cabergoline Side Effects
A few less frequent but nonetheless potential adverse effects of cabergoline include sleeplessness, disorientation, and mental health conditions like anxiety, sadness, and hallucinations. Those who are older or have a history of mental health issues are especially susceptible to these adverse effects. Rarely, excessive libido, compulsive gambling, and other impulse control issues can be brought on by cabergoline (Del Dotto & Bonuccelli, 2003).
There have also been reports of skin problems, including urticaria, itching, and rash, in certain cabergoline recipients. Haematological diseases including leukopenia and thrombocytopenia have been seen in rare instances. Extended usage of high-dose cabergoline has been linked to reports of fibrotic responses, such as retroperitoneal, pericardial, and pulmonary fibrosis.
Serious Cabergoline Side Effects
Although abrupt onset of sleep is one of the rare serious adverse effects of cabergoline, it can happen, especially in Parkinson’s disease patients. If this occurs while performing tasks like operating machines or driving, it might be harmful. Rare instances of heart rhythm problems, such as atrial fibrillation, have also been documented. In the event that symptoms like palpitations, fainting, or chest discomfort materialise, prompt medical attention is necessary.
Rarely, liver disease has been linked to the usage of dopamine agonists like cabergoline. Inform the doctor straight away if you experience any symptoms, including dark urine, itching, yellowing of the skin or eyes, or discomfort in the upper right abdomen. In the event that liver damage is suspected, cabergoline should be stopped.
Patients should contact their physician right away if they have any worrying or long-lasting adverse effects while using cabergoline since there is a chance of significant side effects. Monitoring on a regular basis by a medical expert is necessary to determine tolerability and identify issues early on.
Warnings
Cabergoline usage has to be cautious in particular patient populations and circumstances. Given that the safety of the medicine in these groups has not been completely proven, women who are pregnant or nursing should refrain from using cabergoline. According to Tang et al. (2012), cabergoline has been associated in animal experiments with a higher incidence of congenital abnormalities and miscarriage. It also has the potential to impede breastfeeding because of its inhibitory action on prolactin.
Cabergoline usage should be exercised with caution in patients who already have cardiac disease, such as pericarditis or valvular disease. Patients using dopamine agonists have reported worsening or problems from these disorders. Additionally, individuals with severe renal or hepatic impairment should utilise cabergoline with caution as the drug’s pharmacokinetics and metabolism may be impacted in these populations (Del Dotto & Bonuccelli, 2003).
When using cabergoline, patients with a history of mental illnesses including psychosis, mania, or severe depression should be properly watched. In susceptible patients, dopamine agonists have been connected to the development or exacerbation of mental symptoms. It could be necessary to decrease the dosage or stop taking cabergoline if concerning mental changes start to appear.
Cabergoline should not be abruptly stopped or have its dosage suddenly reduced as this might result in dopaminergic agonist withdrawal syndrome. The symptoms of this condition include weariness, worry, sadness, and widespread discomfort. If medication cannot be stopped, a gradual dosage decrease under physician supervision is advised.
It is important for patients and medical professionals to understand the risks and safety measures related to using cabergoline. To maximise the safety and effectiveness of treatment with this powerful pharmacological agent, careful patient selection, routine monitoring, and customised dosage modification are necessary.
Precautions
Patients who have a history of retroperitoneal fibrotic disease, pericardial fibrosis, or pulmonary fibrosis should use cabergoline with caution since it has been shown to aggravate these illnesses (Colao et al., 2000). Because cabergoline may hasten the course of pre-existing valvular heart disease, patients should have frequent echocardiograms while receiving therapy.
Dopamine agonist withdrawal syndrome, which manifests as apathy, exhaustion, despair, restlessness, and widespread discomfort, may arise from abruptly stopping cabergoline (Del Dotto & Bonuccelli, 2003). If stopping the medication is necessary, a gradual dosage reduction under physician supervision is advised.
When driving or using equipment, the fast onset of sleep and sleepiness caused by caffeine might be risky. Patients should be made aware of this danger and instructed not to partake in these activities if they feel too sleepy.
Contraindications
Patients who have a history of known hypersensitivity to cabergoline or any of the drug’s excipients should not use cabergoline. Cabergoline should not be used by anybody who has a history of psychotic illnesses or severe mental illness as it may exacerbate these problems.
Because it can have major negative effects on the developing foetus or nursing child, cabergoline usage is not advised during pregnancy or lactation. Research on animals has connected cabergoline to congenital defects and an increased chance of miscarriage (Tang et al., 2012). Furthermore, because cabergoline suppresses prolactin, it prevents lactation. During therapy, women who are or may get pregnant should take an effective form of contraception.
Patients with uncontrolled hypertension should not use capetellone since it may induce abrupt decreases in blood pressure. Additionally, cabergoline should not be used by anybody with significant liver or renal failure since this may affect the drug’s clearance, increasing the possibility of adverse effects.
Interactions
Other medications and caffeine may interact, changing the pharmacokinetics or pharmacodynamics of each. Erythromycin, ketoconazole, and ritonavir are examples of medications that block the CYP3A4 enzyme and may raise blood levels of cabergoline, increasing the risk of negative effects (Colao et al., 2000). On the other hand, medications like phenytoin and rifampicin that activate CYP3A4 may lower the levels of cabergoline and lessen its efficacy.
Cabergoline should be used cautiously when combined with other dopamine agonists or medications that impact the dopaminergic system, such as levodopa. An increased risk of side effects, including nausea, vertigo, and orthostatic hypotension, may result from this combination (Del Dotto & Bonuccelli, 2003). It might be essential to carefully monitor and alter dosage in order to maximise safety and effectiveness.
Overdose
Serious adverse effects can result from a cabergoline overdose, primarily from excessive dopamine receptor activation. Nausea, vomiting, dizziness, hypotension, disorientation, and hallucinations are some of the symptoms of an overdose. A significant overdose of cabergoline may result in death, cardiac arrhythmias, and coma.
Supportive approaches for managing a cabergoline overdose include maintaining vital signs, protecting the airway, and giving intravenous fluids. If the overdose is identified early on, gastric lavage or the introduction of activated charcoal may be helpful. Metoclopramide is one antiemetic medication that can be used to lessen nausea and vomiting.
A specialised counteragent exists for overdosing on cabergoline. To counteract the consequences of dopamine receptor overstimulation, dopamine antagonists such domperidone or metoclopramide may be helpful (Tang et al., 2012). Severe overdose situations require close observation in an intensive care unit until the patient’s health stabilises.
In brief
Dopamine agonists like cabergoline are mainly used to treat Parkinson’s disease and hyperprolactinemia. It functions by enhancing dopamine D2 receptors, preventing pituitary gland prolactin release, and reducing Parkinson’s disease-related motor symptoms. It has also been used off-label to treat fibrosing dysplasia and acromegaly.
Frequent adverse effects of cabergoline include headache, nausea, exhaustion, and dizziness. Less often occurring but potentially dangerous side effects include fibrotic responses, valvular heart disease, and impulse control problems. Patients with a history of fibrotic illnesses or those with pre-existing cardiac or psychological issues should utilise cabergoline with caution.
Because of the potential for foetal damage and lactation inhibition, cabergoline should not be used during pregnancy or breastfeeding. It might interact with other medications that impact the dopaminergic system or the CYP3A4 enzyme, necessitating careful monitoring or dose adjustments. Overdosing on caffeine can have major negative effects and need emergency medical attention.
For the treatment of a number of illnesses, cabergoline is a pharmacological substance that is both effective and typically well-tolerated. However, in order to maximise therapeutic efficacy and reduce safety hazards, its administration necessitates careful patient selection, routine monitoring, and a customised strategy.
ATTENTION: It is of vital importance to never take any medication without the supervision and guidance of a specialised doctor. Consult the package insert of each prescribed medicinal product, as each pharmaceutical company accurately describes the specific specifications for the product, which may undergo regular updates. Note that the trade names mentioned in this article correspond to well-known medicinal products that contain the active substances under analysis. However, there may be variations depending on the composition of each drug. This article focuses on the active substance analysis rather than the drug’s trade name. The reference to trade names is made exclusively for the convenience of readers, who should carefully study the instruction leaflet for each commercial preparation they use. It is necessary to have close cooperation with your attending physician and your pharmacist. The self-administration of any medication carries serious health risks and should be strictly avoided.
Bibliography
- A Colao, G Lombardi, L Annunziato – Expert Opinion on Pharmacotherapy, 2000 – Taylor & Francis tandfonline
- P Del Dotto, U Bonuccelli – Clinical Pharmacokinetics, 2003 – Springer link.springer
- H Tang, T Hunter, Y Hu, SD Zhai – Cochrane Database of Systematic Reviews, 2012 cochranelibrary
