VERQUVO 2.5 MG

Indications

• Chronic heart failure with reduced ejection fraction
• Patients stabilised after a recent decompensation event requiring intravenous therapy

Dosage

Adults: Initial dose of 2.5 mg once daily, which may be increased to 5 mg once daily after 2 weeks if tolerated. Further increases can be made to a maximum of 10 mg once daily based on clinical response.

Mechanism of action

Vericiguat directly stimulates soluble guanylate cyclase (sGC) by binding to a specific site on its beta-subunit. This action increases the production of intracellular cGMP, independent of nitric oxide (NO). The rise in cGMP levels promotes vascular smooth muscle relaxation and vasodilation, addressing the vascular dysfunction associated with heart failure.

Pharmacodynamics

The direct stimulation of cGMP production by vericiguat leads to relaxation of vascular smooth muscle, resulting in vasodilation. The drug has a relatively long half-life of approximately 30 hours, allowing for once-daily dosing. However, studies have indicated potential embryo-fetal toxicity, highlighting the importance of excluding pregnancy prior to initiation of therapy and the necessity of effective contraception during and after treatment.

Pharmacokinetics

Vericiguat exhibits a half-life of around 30 hours, which supports its once-daily administration. The pharmacokinetics of vericiguat suggest that it is absorbed well following oral administration, although specific details regarding its metabolism and excretion are not provided in the available literature.

Contra-indications

• Hypotension (do not initiate if systolic blood pressure less than 100 mmHg)

Adverse effects

• Hypotension
• Headache
• Dizziness
• Nausea
• Vomiting
• Angioedema

Interactions

• Other antihypertensives may enhance hypotensive effects
• Caution with concomitant use of nitrates or PDE5 inhibitors

Precautions

• Caution in patients with autonomic dysfunction
• History of angioedema associated with ACE inhibitors
• Consider a starting dose of 24/26 mg if systolic blood pressure is less than 110 mmHg

Pregnancy

Animal reproduction studies have shown potential for embryo-fetal toxicity, including defects in major vessel and heart formation. Pregnancy should be excluded prior to starting therapy, and effective contraception is advised during treatment and for one month after discontinuation.

Breast-feeding

There are no available data on the excretion of vericiguat in human milk, and caution should be exercised.

Storage

Store at room temperature, protect from moisture and light.

Formulations

• Tablets: 2 mg, 5 mg, and 10 mg

Mechanism of action

Heart failure (HF) involves, amongst other morphologic and physiologic changes, the impaired synthesis of nitric oxide (NO) and decreased activity of soluble guanylate cyclase (sGC). Functioning normally, NO binds to sGC and stimulates the synthesis of intracellular cyclic guanosine monophosphate (cGMP), a second messenger involved in the maintenance of vascular tone, as well as cardiac contractility and remodeling. Defects in this pathway are thought to contribute to the myocardial and vascular dysfunction associated with heart failure and are therefore a desirable target in its treatment. Vericiguat directly stimulates sGC by binding to a target site on its beta-subunit, bypassing the need for NO-mediated activation, and in doing so causes an increase in the production of intracellular cGMP that results in vascular smooth muscle relaxation and vasodilation.

Pharmacodynamics

By directly stimulating the increased production of intracellular cyclic guanosine monophosphate (cGMP), vericiguat causes the relaxation of vascular smooth muscle and vasodilation. Vericiguat has a relatively long half-life (~30h) that allows for once-daily dosing. Animal reproduction studies have demonstrated the potential for embryo-fetal toxicity when vericiguat is administered to pregnant females - defects in major vessel and heart formation, as well as spontaneous abortions/resorptions, were observed when vericiguat was administered to pregnant rabbits during organogenesis. The possibility of pregnancy should be excluded prior to beginning therapy with vericiguat, and adequate contraception should be used throughout therapy and for one month following cessation of treatment.