5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Calcium channel blockers, Dihydropyridine derivatives, ATC code: C08CA09.

Mechanism of Action:

MOTENS 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, MOTENS 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 MOTENS.

Following the oral administration of 4 mg lacidipine 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.

5.2 Pharmacokinetic properties
Absorption:

MOTENS 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.

Metabolism:

The drug is eliminated primarily by hepatic metabolism (involving cytochrome P450 CYP3A4). There is no evidence that MOTENS causes either induction or inhibition of hepatic enzymes.

The principal metabolites possess little, if any, pharmacodynamic activity.

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 MOTENS ranges from between 13 and 19 hours at steady state.

5.3 Preclinical safety data
In acute toxicity studies, MOTENS has shown a wide safety margin.

In repeated dose toxicological studies, findings in animals, related to the safety profile of MOTENS in man, were reversible and reflected the pharmacodynamic effect of MOTENS.

No data of clinical relevance have been gained from in vivo and in vitro studies on reproduction toxicity, genetic toxicity or oncogenicity.

6. Pharmaceutical particulars
6.1 List of excipients
Tablet core:

Lactose (monohydrate)

Lactose (spray-dried)

Povidone K30

Magnesium stearate

Film coating:

Titanium Dioxide (E 171)

PEG 400

Polysorbate 80

Methylhydroxypropylcellulose

6.2 Incompatibilities
Not applicable.

6.3 Shelf life
2 years

6.4 Special precautions for storage
Do not store above 30 °C.

MOTENS is light sensitive. MOTENS tablets should, therefore, be stored in the original container and should not be removed from their foil pack until required for administration.

6.5 Nature and contents of container
Double foil blister pack or child-resistant foil blister pack.

Cartons containing 7, 14 and 28 tablets packed in blister strips.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling
No special