Relaxin-2 (Serelaxin), explained simply

Relaxin-2 attaches to RXFP1/RXFP2 receptors (its docking sites) on the lining of blood vessels and widens them, which predictably lowers resistance to blood flow and blood pressure. ^{6Source 6A randomized, double-blind, placebo-controlled, multicentre study to assess haemodynamic effects of serelaxin in patients with acute heart failurePonikowski P, Mitrovic V, Ruda M, et al. · 20147Source 7Relaxin family peptides and their receptorsBathgate RAD, Halls ML, van der Westhuizen ET, Callander GE, Kocan M, Summers RJ · 201311Source 11RELAX-AHF-2: Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF — study results (NCT01870778)Novartis Pharmaceuticals / ClinicalTrials.gov · 2019} This depends on the dose and is strongest in the first 24 hours of IV infusion, with systolic blood pressure typically dropping 10-20 mmHg.

What to do Establish baseline blood pressure before infusion. Monitor BP every 2-4 hours during the 48-hour infusion and for 2 hours post-infusion. Position patient semi-recumbent or upright to promote venous return. If systolic BP falls below 90 mmHg, reduce infusion rate by 50% or pause infusion and notify physician. Ensure adequate hydration. Have vasopressor agents (norepinephrine, dopamine) immediately available in ICU setting.

The heart speeds up to make up for wider blood vessels and lower resistance to blood flow. ^{2Source 2Relaxin and the Cardiovascular System: from Basic Science to Clinical PracticeMartins RC, et al. · 20207Source 7Relaxin family peptides and their receptorsBathgate RAD, Halls ML, van der Westhuizen ET, Callander GE, Kocan M, Summers RJ · 201311Source 11RELAX-AHF-2: Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF — study results (NCT01870778)Novartis Pharmaceuticals / ClinicalTrials.gov · 2019} Heart rate typically rises 5-15 bpm as the body's pressure sensors react normally, though some patients have a reflex rate above 100 bpm.

What to do Monitor heart rate continuously during the infusion. Record baseline and post-infusion rates. A fast heart rate typically settles as blood pressure stabilizes. If heart rate goes above 120 bpm or the patient reports palpitations, notify the physician, as this may mean a rhythm problem or poorly controlled pain. Keep the patient hydrated and avoid sudden position changes.

Relaxin widens blood vessels in the brain, and with other blood pressure changes this can trigger or worsen headaches. ^{8Source 8Maternal vasodilation in pregnancy: the emerging role of relaxinConrad KP · 201111Source 11RELAX-AHF-2: Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF — study results (NCT01870778)Novartis Pharmaceuticals / ClinicalTrials.gov · 2019} Occurs in approximately 5-10% of infusion recipients, typically mild to moderate.

What to do Administer acetaminophen (500-1000mg) or NSAIDs if not contraindicated for AHF patients. Ensure dark, quiet environment. Apply cool compresses to temples. Assess BP—hypotension-induced headaches resolve when BP normalizes. Maintain hydration. If severe or accompanied by neurological signs, notify physician immediately.

Nausea can result from acute hemodynamic changes, IV administration discomfort, or medication interactions. ^{11Source 11RELAX-AHF-2: Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF — study results (NCT01870778)Novartis Pharmaceuticals / ClinicalTrials.gov · 2019} Generally mild and transient, occurring during initial hours of infusion.

What to do Premedicate with ondansetron (4-8mg IV) or metoclopramide (10mg IV) if nausea anticipated. Avoid food 1-2 hours before and during infusion. Maintain NPO status per institutional protocol. Monitor hydration status. Most nausea resolves within first 12 hours. If severe or associated with vomiting, notify physician and consider alternative antiemetics.

Dizziness or lightheadedness results from acute blood pressure reduction and changes in cerebral perfusion. ^{11Source 11RELAX-AHF-2: Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF — study results (NCT01870778)Novartis Pharmaceuticals / ClinicalTrials.gov · 2019} Risk increases with rapid infusion rate or inadequate hydration. More common in elderly or volume-depleted patients.

What to do Maintain semi-recumbent position to enhance cerebral perfusion. Move slowly when changing positions. Ensure adequate hydration per heart failure protocol. Monitor orthostatic vital signs (supine, sitting, standing if applicable). Reduce infusion rate if dizziness severe. Assess for concurrent medication effects (narcotics, sedatives). Notify physician if accompanied by syncope risk.

Relaxin makes blood vessel walls leakier, and salt and fluid build up in acute heart failure. Together these can cause or worsen swelling, especially in low-lying areas (ankles, or the lower back in bed-bound patients). It may also reflect better blood flow letting the kidneys handle fluid better.

What to do Weigh the patient daily, before and after the infusion. Check how bad the foot and ankle swelling is and where it sits. Raise the legs above heart level when resting. Use compression stockings if ordered. Keep up the water pills (diuretics) as set by cardiology. Check for skin infection or skin breakdown from long-standing swelling. Tell the physician if swelling gets worse despite appropriate diuretic treatment.

Serum creatinine may transiently rise during infusion due to reduced renal perfusion pressure from hypotension or intrinsic glomerular effects. ^{1Source 1End-organ protective effect of serelaxin in patients hospitalized for heart failure: Results of the biomarker substudy of Relaxin in Acute Heart Failure-2 (RELAX-AHF-2)Voors AA, et al. · 202511Source 11RELAX-AHF-2: Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF — study results (NCT01870778)Novartis Pharmaceuticals / ClinicalTrials.gov · 2019} Typically reversible post-infusion as hemodynamics normalize. Can reflect acute tubular necrosis risk in pre-existing renal disease.

What to do Draw baseline creatinine and BUN before infusion start. Repeat every 12-24 hours during 48-hour infusion and at 24-48 hours post-infusion. Calculate eGFR to assess glomerular filtration rate trend. If creatinine increases >0.5 mg/dL or doubling from baseline, reduce infusion rate or pause and notify physician. Ensure adequate hydration. Monitor urine output for oliguria. Hold ACE-I/ARB per institutional protocol during infusion.

Acute kidney injury risk and potential aldosterone suppression from improved renal hemodynamics can elevate serum potassium. ^{11Source 11RELAX-AHF-2: Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF — study results (NCT01870778)Novartis Pharmaceuticals / ClinicalTrials.gov · 2019} Risk increases in patients with baseline renal impairment (eGFR <30) or on ACE-I/ARB therapy.

What to do Draw baseline potassium before infusion. Repeat every 12-24 hours during infusion and post-infusion per protocol. If K+ exceeds 5.5 mEq/L, notify physician immediately. Restrict potassium intake during hospitalization. Hold potassium supplements and potassium-sparing agents. Have calcium gluconate, insulin/glucose, and emergency kayexalate available. Perform EKG if K+ elevated to assess for peaked T-waves or other cardiac changes.

Profound hypotension combined with positive chronotropic effects can precipitate vasovagal syncope or hypotensive episodes, particularly with sudden position changes or straining. ^{11Source 11RELAX-AHF-2: Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF — study results (NCT01870778)Novartis Pharmaceuticals / ClinicalTrials.gov · 2019} Risk highest in first 24 hours of infusion.

What to do Maintain patient on continuous cardiac telemetry. Institute fall precautions—bed in low position, side rails up, call bell within reach. Assist with all position changes and ambulation. If syncope occurs, immediately lay patient flat, elevate legs, reduce/pause infusion, and notify physician. Assess for injuries from fall. May require vasopressor support or infusion rate reduction. Hold patient in ICU setting post-syncope.

Acute hemodynamic changes, atrial dilation from HF, or catecholamine surges can trigger atrial fibrillation de novo or exacerbate pre-existing AF. ^{11Source 11RELAX-AHF-2: Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF — study results (NCT01870778)Novartis Pharmaceuticals / ClinicalTrials.gov · 2019} Occurs in 2-5% of infusion recipients, particularly those with structural heart disease or elevated filling pressures.

What to do Maintain continuous cardiac telemetry throughout infusion. Obtain baseline 12-lead EKG before infusion. If AF develops, notify physician immediately. Do not delay intervention. Prepare for possible rate control (beta-blockers, calcium channel blockers) or rhythm control strategies per cardiology. Ensure adequate anticoagulation if not already on anticoagulant. Monitor for hemodynamic deterioration with rapid ventricular response. Have emergency equipment available.

Continuous monitoring of blood pressure and circulation is essential, because relaxin-2 widens blood vessels and can lower blood pressure sharply. Catch low blood pressure early. ^{6Source 6A randomized, double-blind, placebo-controlled, multicentre study to assess haemodynamic effects of serelaxin in patients with acute heart failurePonikowski P, Mitrovic V, Ruda M, et al. · 2014} Arterial line (a catheter in an artery) or cuff monitoring every 1-4 hours shows the blood pressure trend and how well the infusion is tolerated.

What to do Establish continuous non-invasive BP monitoring (automatic cuff every 2-4 hours minimum) or invasive arterial line for closer monitoring. Position BP cuff at heart level for accuracy. Document systolic, diastolic, and mean arterial pressures. Plot trend on chart to visualize hemodynamic response. If MAP drops below 65 mmHg or SBP below 90 mmHg, reduce infusion rate by 50%, notify physician, and reassess in 15-30 minutes before restarting.

Acute kidney function assessment is critical because hypotension and intrinsic renal effects from relaxin can precipitate acute kidney injury. ^{11Source 11RELAX-AHF-2: Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF — study results (NCT01870778)Novartis Pharmaceuticals / ClinicalTrials.gov · 2019} Baseline renal function predicts risk—patients with eGFR <30 are at higher risk for worsening function.

What to do Draw baseline serum creatinine, BUN, and calculate eGFR before infusion. Repeat creatinine every 12-24 hours during 48-hour infusion. Monitor 24-hour urine creatinine and urine electrolytes per protocol. Assess urine output hourly (target >0.5 mL/kg/hr). If creatinine rises >0.5 mg/dL acutely, reduce infusion rate and ensure adequate hydration. Hold nephrotoxic agents. Consider contrast avoidance for any imaging during treatment window.

Acute shifts in serum electrolytes (sodium, potassium, magnesium) occur from hemodynamic changes, diuretic therapy, and altered renal handling. ^{10Source 10Safety and tolerability of serelaxin, a recombinant human relaxin-2 in development for the treatment of acute heart failure, in healthy Japanese volunteers and a comparison of pharmacokinetics and pharmacodynamics in healthy Japanese and Caucasian populationsDahlke M, Ng D, Yamaguchi M, et al. · 2015} Hyponatremia and hyperkalemia represent the primary electrolyte concerns during relaxin infusion.

What to do Draw baseline comprehensive metabolic panel (CMP) before infusion including Na+, K+, Mg2+, Cl-. Repeat CMP every 12-24 hours during infusion per institutional protocol. Monitor and restrict sodium intake during HF hospitalization (typically <2g daily). Supplement potassium only if serum K+ <3.5 mEq/L. Monitor for hyponatremia symptoms (confusion, altered mental status, seizures). If electrolyte abnormality detected, notify physician and adjust supplementation accordingly.

Continuous cardiac monitoring captures the heart rate response to hemodynamic changes and detects arrhythmias. ^{11Source 11RELAX-AHF-2: Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF — study results (NCT01870778)Novartis Pharmaceuticals / ClinicalTrials.gov · 2019} Telemetry surveillance is mandatory during 48-hour infusion given the potent hemodynamic effects of relaxin.

What to do Start continuous heart monitoring before the infusion begins. Track heart rate, rhythm, and the PR and QT intervals (timing measurements on the heart tracing). Get a baseline 12-lead EKG before the infusion. Watch for new rhythm problems, including atrial fibrillation (AF), extra beats (PACs, PVCs), or conduction problems. If a serious rhythm problem develops (sustained ventricular tachycardia, a heart rate under 50, or AF with a heart rate over 120), notify the physician immediately and be ready to intervene. Keep monitoring for 2+ hours after the infusion.

Diuresis or oliguria responses to relaxin infusion depend on baseline renal function and hemodynamics. Expected response is improved urine output (>1-1.5 L/24hr in most) as renal perfusion improves. ^{10Source 10Safety and tolerability of serelaxin, a recombinant human relaxin-2 in development for the treatment of acute heart failure, in healthy Japanese volunteers and a comparison of pharmacokinetics and pharmacodynamics in healthy Japanese and Caucasian populationsDahlke M, Ng D, Yamaguchi M, et al. · 201517Source 17Serelaxin as a potential treatment for renal dysfunction in cirrhosis: Preclinical evaluation and results of a randomized phase 2 trialSnowdon VK, Lachlan NJ, Hoy AM, et al. · 2017} Oliguria (<400-500 mL/24hr) signals acute kidney injury.

What to do Insert Foley catheter and monitor urine output hourly during infusion. Document color, clarity, and specific gravity. Target urine output >0.5 mL/kg/hr (approximately 30-40 mL/hr for average adult). If output <0.3 mL/kg/hr, assess fluid status, reduce infusion rate if hypotensive, and notify physician—may indicate acute kidney injury. Maintain accurate I/O records. Send urine for urinalysis and electrolytes if oliguria develops.

Rarely, relaxin may cause large blood pressure changes or heart complications, especially in people with existing heart conditions. ^{11Source 11RELAX-AHF-2: Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF — study results (NCT01870778)Novartis Pharmaceuticals / ClinicalTrials.gov · 2019} The most serious are cardiogenic shock (the heart cannot pump enough blood; systolic blood pressure under 90 mmHg that does not respond to fluids), fluid in the lungs that is not clearing and needs a breathing machine, or severe heart rhythm problems that need advanced life support.

What to do Cease infusion immediately if SBP falls below 90 mmHg unresponsive to rate reduction and fluid administration. Notify physician and cardiology emergently. Initiate vasopressor support (norepinephrine, dopamine, dobutamine) if cardiogenic shock develops. Have emergency intubation equipment and advanced cardiac life support (ACLS) protocols readily available. If chest pain, severe dyspnea, or syncope occurs, this is a medical emergency—call 911 if outside hospital. In hospital, follow code protocols and cardiology guidance immediately.