Symptoms
There have been no recorded cases of Monopin tablets overdosage. The expected symptoms could comprise prolonged peripheral vasodilation associated with hypotension and tachycardia. Bradycardia or prolonged AV conduction could occur.
Therapy
There is no specific antidote. Standard general measures for monitoring cardiac function and appropriate supportive and therapeutic measures should be used.
Monopin tablets are contraindicated in patients with known hypersensitivity to any ingredient of the preparation.
Monopin should only be used with great care in patients with a previous allergic reaction to another dihydropyridine because there is a theoretical risk of cross-reactivity.
As with other calcium antagonists, Monopin should be discontinued in patients who develop cardiogenic shock and unstable angina. In addition, dihydropyridines have been shown to reduce coronary arterial blood-flow in patients with aortic stenosis and in such patients Monopin is contraindicated.
Monopin should not be used during or within one month of a myocardial infarction.
) the use of the product is contraindicated.Not applicable.
Monopin tablets are generally well tolerated.
Some individuals may experience minor side effects which are related to its known pharmacological action of peripheral vasodilation. Such effects, indicated by a hash #, are usually transient and usually disappear with continued administration of Monopin at the same dosage.
Data from large clinical studies (internal and published) were used to determine the frequency adverse effects.
Adverse effects have been ranked under headings of frequency using the following convention:
| very common: common: uncommon: rare: very rare: not known: | >1/10 > 1/100, <1/10 > 1/1000, <1/100 > 1/10000, <1/1000 <1/10000 cannot be estimated from the available data |
In each group adverse effects are presented with decreasing severity.
| Pysichiatric disorders | |
| Very rare: | depression |
| Nervous system disorders | |
| Common: | #headache, #dizziness |
| Very rare: | tremor |
| Cardiac disorders | |
| Common: | #palpitations, tachycardia |
| Uncommon: | syncope, hypotension |
As with other dihydropyridines aggravation of underlying angina pectoris has been reported in a small number of individuals, especially at the start of treatment. This is more likely to happen in patients with symptomatic ischaemic heart disease. Monopin should be discontinued under medical supervision in patients who develop unstable angina. Vascular disorders | |
| Common: | #flushing (especially of face) |
| Uncommon: | hypotension |
| Gastrointestinal disorders | |
| Common: | abdominal discomfort, nausea |
| Uncommon: | gingival hyperplasia |
| Skin and subcutaneous tissue disorders | |
| Common: | rash, erythema, pruritus |
| Rare: | angioedema, urticaria |
| Musculoskeletal and connective tissue disorders | |
| Rare: | muscle cramps |
| Renal and urinary disorders | |
| Common: | polyuria |
| General disorders and administration site conditions | |
| Common: | asthenia, #oedema |
| Investigations | |
| Common: | blood alkaline phosphatase increased |
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme: www.mhra.gov.uk/yellowcard.
In acute toxicity studies, Monopin has shown a wide safety margin.
In repeated dose toxicological studies, findings in animals, related to the safety profile of Monopin in man, were reversible and reflected the pharmacodynamic effect of Lacydipine.
No data of clinical relevance have been gained from in vivo and in vitro studies on reproduction toxicity, genetic toxicity or oncogenicity.
Monopin is indicated for the treatment of hypertension either alone or in combination with other antihypertensive agents, including ß-adrenoceptor antagonists, diuretics, and ACE-inhibitors.
Pharmacotherapeutic group: Calcium channel blockers, dihydropyridine derivatives
ATC code: C08CA09
Mechanism of action
Monopin is a specific and potent calcium antagonist with a predominant selectivity for calcium channels in the vascular smooth muscle.
Pharmacodynamic effects
Its main action is to dilate peripheral arterioles, reducing peripheral vascular resistance and lowering blood pressure.
In a study of ten patients with a renal transplant, Monopin has been shown to prevent an acute decrease in renal plasma flow and glomerular filtration rate about six hours after administering oral cyclosporin. During the trough phase of cyclosporin treatment, there was no difference in renal plasma flow and glomerular filtration rate between patients with or without Monopin.
Following the oral administration of 4 mg Monopin to volunteer subjects, a minimal prolongation of QTc interval has been observed (mean QTcF increase between 3.44 and 9.60 ms in young and elderly volunteers). This was not associated with any adverse clinical effects or cardiac arrhythmias on monitoring.
Absorption
Monopin is a highly lipophilic compound; it is rapidly absorbed from the gastrointestinal tract following oral dosing.
Absolute bioavailability averages about 10% due to extensive first-pass metabolism in the liver.
Peak plasma concentrations are reached between 30 and 150 minutes.
Biotransformation
The principal four metabolites possess little, if any, pharmacodynamic activity.
The drug is eliminated primarily by hepatic metabolism (involving cytochrome P450 CYP3A4). There is no evidence that Monopin causes either induction or inhibition of hepatic enzymes.
Elimination
Approximately 70% of the administered dose is eliminated as metabolites in the faeces and the remainder as metabolites in the urine.
The average terminal half-life of Monopin ranges from between 13 and 19 hours at steady state.
In specialised studies Monopin has been shown not to affect the spontaneous function of the SA node or to cause prolonged conduction within the AV node. However, the theoretical potential for a calcium antagonist to affect the activity of the SA and AV nodes should be noted, and therefore Monopin should be used with caution in patients with pre-existing abnormalities in the activity of the SA and AV nodes.
As has been reported with other dihydropyridine calcium channel antagonists, Monopin should be used with caution in patients with congenital or documented acquired QT prolongation. Monopin should also be used with caution in patients treated concomitantly with medications known to prolong the QT interval such as class I and III antiarrhythmics, tricyclic antidepressants, some antipsychotics, antibiotics (e.g. erythromycin) and some antihistamines (e.g. terfenadine).
As with other calcium antagonists, Monopin should be used with caution in patients with poor cardiac reserve.
There is no evidence that Monopin is useful for secondary prevention of myocardial infarction.
The efficacy and safety of Monopin in the treatment of malignant hypertension has not been established.
Monopin should be used with caution in patients with impaired liver function because antihypertensive effect may be increased.
There is no evidence that Monopin impairs glucose tolerance or alters diabetic control.
Excipients
This product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Monopin tablets may cause dizziness. Patients should be warned not to drive or operate machinery if they experience dizziness or related symptoms.
Posology
Adults
The treatment of hypertension should be adapted to the severity of the condition, and according to the individual response.
The recommended initial dose is 2 mg once daily. The dose may be increased to 4 mg (and then, if necessary, to 6 mg) after adequate time has been allowed for the full pharmacological effect to occur. In practice, this should not be less than 3 to 4 weeks. Daily doses above 6 mg have not been shown to be significantly more effective. Monopin tablets should be taken at the same time each day, preferably in the morning. Treatment with Monopin may be continued indefinitely.
Patients with hepatic impairment
Monopin is metabolised primarily by the liver and therefore in patients with hepatic impairment, the bioavailability of Monopin may be increased and the hypotensive effect enhanced. These patients should be carefully monitored, and in severe cases, a dose reduction may be necessary.
Patients with kidney disease
As Monopin is not cleared by the kidneys, the dose does not require modification in patients with kidney disease.
Paediatric population
The safety and efficacy of Monopin in children and adolescents aged below 18 have not been estabilished. No data are available.
Method of administration
For oral administration
The tablets should not be removed from their foil pack until required for administration.
No special requirements for disposal.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
