NIFELAT RETARD 20MG TABLET

Indications

• Hypertension
• Angina pectoris (prophylaxis)

Dosage

Children: Not licensed for use in children.

Adults: Initially 5 mg three times a day, which may be adjusted according to response, with a typical maintenance dose of 10-20 mg three times a day. For modified-release formulations, the initial dose is often 20 mg twice daily.

Mechanism of action

Nifedipine blocks voltage-gated L-type calcium channels in vascular smooth muscle and myocardial cells. This action prevents calcium ions from entering the cells during depolarization, reducing peripheral arterial resistance and dilating coronary arteries. This results in lowered blood pressure and increased oxygen delivery to the heart, alleviating angina symptoms. The mechanism by which nifedipine inhibits calcium influx is not completely understood, but it is believed to involve interference with ion-control gating mechanisms of the calcium channels.

Pharmacodynamics

Nifedipine is an inhibitor of L-type voltage-gated calcium channels, which reduces blood pressure and increases oxygen supply to the heart. The immediate-release formulations require dosing three times daily due to their shorter duration of action. The typical daily dose ranges from 10 to 120 mg, with careful monitoring for excessive hypotension and potential angina exacerbation.

Pharmacokinetics

Nifedipine is rapidly absorbed following oral administration, with peak plasma concentrations typically occurring within 30 minutes to 2 hours for immediate-release forms. Its bioavailability is affected by first-pass metabolism, and it is extensively metabolized in the liver. The half-life of nifedipine varies, but it generally ranges from 2 to 5 hours. The drug is primarily excreted as metabolites in the urine, with only a small fraction excreted unchanged.

Contra-indications

• Cardiogenic shock
• Aortic stenosis
• Severe maternal hypotension
• Fatal fetal hypoxia in pregnancy

Adverse effects

• Constipation
• Malaise
• Oedema
• Allergic reactions
• Angioedema
• Hypotension
• Reflex tachycardia

Interactions

• Grapefruit juice (severe increase in exposure)
• Rifampicin (severe decrease in exposure)
• Enzalutamide (moderate decrease in exposure)
• Dronedarone (moderate increase in exposure)
• Antifungal azoles (moderate increase in exposure)
• Miconazole (moderate increase in exposure)
• Cobicistat (moderate increase in exposure)
• Crizotinib (moderate increase in exposure)
• Dabrafenib (moderate decrease in exposure)
• Idelalisib (moderate increase in exposure)

Precautions

• Monitor blood pressure and heart rate regularly
• Use with caution in patients with significant left ventricular dysfunction
• Avoid excessive decrease in blood pressure
• Consider initial low doses in patients with renal impairment

Pregnancy

May inhibit labour; not to be used in multiple pregnancies unless no other acceptable alternative.

Breast-feeding

Manufacturer advises to avoid; present in breast milk.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Immediate-release capsules
• Modified-release formulations
• Oral suspension
• Solution for infusion

Indications

• Bacterial infections
• Infections caused by susceptible organisms
• Prophylaxis in certain surgical procedures

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations based on age, weight, and condition.

Adults: Refer to the BNF for specific dosages based on the condition being treated, severity of infection, and patient factors.

Mechanism of action

Release exerts its effects by inhibiting bacterial cell wall synthesis, leading to cell lysis and death. This mechanism is primarily mediated through the disruption of peptidoglycan cross-linking, which is essential for maintaining the structural integrity of bacterial cell walls.

Pharmacodynamics

The pharmacodynamics of Release involves its bactericidal action against a wide range of gram-positive and some gram-negative bacteria. The drug displays a time-dependent killing effect, meaning that its efficacy is related to the duration of exposure rather than the peak concentration achieved. Resistance to Release can develop through various mechanisms, including alterations in target sites or enzymatic degradation.

Pharmacokinetics

Release is absorbed and distributed throughout the body following administration. Peak plasma concentrations are typically achieved within a few hours. The drug is metabolized primarily in the liver, with metabolites excreted via the kidneys. The half-life of Release can vary depending on individual patient factors, including age, liver function, and concurrent medications.

Indications

• Chronic pain management
• Hypertension
• Type 2 diabetes
• Cardiovascular disorders
• Seizure disorders

Dosage

Children: Refer to specific medication guidelines, as dosing varies widely based on the drug and condition being treated.

Adults: Refer to specific medication guidelines, as dosing varies widely based on the drug and condition being treated.

Mechanism of action

Slow-release formulations typically employ polymeric matrices or coating technologies that control the rate of drug release. The mechanisms can include diffusion, erosion, or osmosis, allowing for a sustained release of medication into the systemic circulation. This leads to prolonged therapeutic effects while minimizing peak-trough fluctuations associated with immediate-release formulations.

Pharmacodynamics

The pharmacodynamics of slow-release medications depend on the specific drug being used. Generally, they aim to maintain a steady-state concentration of the drug in the plasma, which enhances efficacy and minimizes side effects. This is particularly important for drugs with narrow therapeutic indices or those that require consistent plasma levels for optimal therapeutic effect.

Pharmacokinetics

The pharmacokinetics of slow-release medications vary based on the drug's properties and the delivery system. Typically, these formulations demonstrate altered absorption rates, leading to a slower peak concentration in the bloodstream. The half-life of the drug may not change; however, the time to reach peak concentration is extended, and the overall exposure (AUC) may increase. Metabolism and excretion rates remain similar to those of immediate-release forms but may influence dosing intervals.

Pregnancy

Consult healthcare provider before use as safety during pregnancy has not been established.

Breast-feeding

Consult healthcare provider before use as it is unknown if this drug is excreted in human milk.

Storage

Store in a cool, dry place away from direct sunlight.

Mechanism of action

Nifedipine blocks voltage gated L-type calcium channels in vascular smooth muscle and myocardial cells. This blockage prevents the entry of calcium ions into cells during depolarization, reducing peripheral arterial vascular resistance and dilating coronary arteries. These actions reduce blood pressure and increase the supply of oxygen to the heart, alleviating angina. The principal physiologic action of nifedipine is to inhibit the transmembrane influx of extracellular calcium ions across the membranes of myocardial cells and vascular smooth muscle cells, without changing serum calcium concentrations. Calcium plays important roles in the excitation-contraction coupling processes of the heart and vascular smooth muscle cells and in the electrical discharge of the specialized conduction cells of the heart. The membranes of these cells contain numerous channels that carry a slow inward current and that are selective for calcium. Activation of these slow calcium channels contributes to the plateau phase (phase 2) of the action potential of cardiac and vascular smooth muscle cells. The exact mechanism whereby nifedipine inhibits calcium ion influx across the slow calcium channels is not known, but the drug is thought to inhibit ion-control gating mechanisms of the channel, deform the slow channel, and/or interfere with release of calcium from the sarcoplasmic reticulum. By inhibiting calcium influx, nifedipine inhibits the contractile processes of cardiac and vascular smooth muscle, thereby dilating the main coronary and systemic arteries. Nifedipine is a peripheral arterial vasodilator which acts directly on vascular smooth muscle. The binding of nifedipine to voltage-dependent and possibly receptor-operated channels in vascular smooth muscle results in an inhibition of calcium influx through these channels. Stores of intracellular calcium in vascular smooth muscle are limited and thus dependent upon the influx of extracellular calcium for contraction to occur. The reduction in calcium influx by nifedipine causes arterial vasodilation and decreased peripheral vascular resistance which results in reduced arterial blood pressure.

Pharmacodynamics

Nifedipine is an inhibitor of L-type voltage gated calcium channels that reduces blood pressure and increases oxygen supply to the heart. Immediate release nifedipine's duration of action requires dosing 3 times daily. Nifedipine dosing is generally 10-120mg daily. Patients should be counselled regarding the risk of excessive hypotension, angina, and myocardial infarction.