Rybelsus 4 — Semaglutide 4 mg Tablets, 30 Tablets

Rybelsus 4 mg is supplied as oval, white to light yellow film-coated tablets for oral administration.

Qualitative and Quantitative Composition per Tablet:

• • Active Ingredient: Semaglutide — 4 mg.
• • Excipients: Salcaprozate sodium (SNAC) — 300 mg, microcrystalline cellulose, povidone K90, magnesium stearate.

Packaging Configuration: 4 mg tablets are packaged in aluminum/aluminum blisters containing 10 tablets per strip. The trade carton contains 30 tablets (3 blisters of 10 tablets), providing a 30-day initial dose titration pack. The carton carries official Novo Nordisk branding, batch details, and prescribing guidelines.

Pharmacodynamics:
Semaglutide is a human GLP-1 receptor agonist with 94% sequence homology to native human GLP-1. It selectively binds to and activates the GLP-1 receptor. Semaglutide reduces blood glucose levels by stimulating insulin secretion and lowering glucagon secretion in a glucose-dependent manner. Additionally, semaglutide delays early postprandial gastric emptying and reduces body weight by decreasing calorie intake through reduced appetite.

Pharmacokinetics:

• • Absorption: Semaglutide absorption occurs predominantly in the stomach via co-formulation with SNAC. Maximum plasma concentration ($C_{max}$) is reached 1–2 hours post-dose. Absolute oral bioavailability is approximately 1%.
• • Distribution: Extensively bound to plasma proteins (>99%). Apparent volume of distribution is approximately 8 liters.
• • Metabolism: Extensively metabolized through proteolytic cleavage of the peptide backbone and beta-oxidation of the fatty acid side chain.
• • Elimination: Terminal elimination half-life ($T_{1/2}$) is approximately 1 week, supporting once-daily oral dosing. Excreted in urine and feces as metabolites.

Rybelsus 4 mg is indicated for the treatment of adults with type 2 diabetes mellitus:

• • Monotherapy: To improve glycemic control when metformin is considered inappropriate due to intolerance or contraindications.
• • Combination Therapy: In combination with other glucose-lowering medicinal products (metformin, sulfonylureas, SGLT2 inhibitors, insulin) when current treatment does not provide adequate glycemic control.

Treatment with Rybelsus 4 mg should be prescribed and monitored by a qualified healthcare professional.

Strict Dosing Administration Rules:

• • Take the tablet on an empty stomach upon waking.
• • Swallow the tablet whole with a sip of plain water (no more than 120 mL / 4 fl oz).
• • Do not chew, crush, or split the tablet.
• • Wait at least 30 minutes before eating, drinking, or taking any other oral medications. Failure to wait reduces semaglutide absorption.

Dosage Regimen and Titration Schedule:

• • Starting Dose: 4 mg once daily for 4 weeks. The 4 mg dose is intended for treatment initiation and is not effective for long-term glycemic control.
• • Dose Escalation: After 4 weeks on 4 mg, escalate the dose to 7 mg once daily.
• • Further Titration: If additional glycemic control is required after at least 4 weeks on 7 mg, the dose may be increased to the maximum maintenance dose of 14 mg once daily.

Missed Dose: If a dose is missed, skip the missed dose and take the next dose the following morning on an empty stomach.

Administration of Rybelsus 4 mg is contraindicated in:

• • Hypersensitivity: Hypersensitivity to semaglutide or any excipients in the formulation.
• • Medullary Thyroid Carcinoma: Personal or family history of medullary thyroid carcinoma (MTC).
• • MEN 2 Syndrome: Patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
• • Type 1 Diabetes: Not indicated for type 1 diabetes mellitus or treatment of diabetic ketoacidosis.
• • Pregnancy and Lactation: Contraindicated during pregnancy and breastfeeding. Discontinue at least 2 months prior to a planned pregnancy.
• • Pediatric Population: Safety and efficacy in patients under 18 years have not been established.

Rybelsus delays gastric emptying, which may impact the absorption rate of concomitantly administered oral medications.

Key Drug Interactions:

• • Thyroid Hormones (Levothyroxine): Exposure to levothyroxine is increased when co-administered. Monitoring of thyroid parameters is recommended.
• • Sulfonylureas and Insulin: Co-administration increases the risk of hypoglycemia. Dose reduction of sulfonylurea or insulin may be required.
• • Oral Contraceptives: No clinically relevant effect on oral contraceptive exposure observed.

Pregnancy:
Data regarding the use of semaglutide in pregnant women are limited. Rybelsus is contraindicated during pregnancy. Due to the long half-life of semaglutide, Rybelsus must be discontinued at least 2 months before planning a pregnancy.

Lactation:
It is unknown whether semaglutide is excreted in human milk. Breastfeeding is contraindicated during treatment with Rybelsus.

Treatment with Rybelsus 4 mg may cause adverse reactions, most commonly involving the gastrointestinal system.

Adverse Reactions:

• • Gastrointestinal (Very Common): Nausea, diarrhea, vomiting, abdominal pain, decreased appetite, constipation, dyspepsia, gastritis. Symptoms occur mainly during dose titration and decrease over time.
• • Hypoglycemia: Common when used in combination with sulfonylureas or insulin.
• • Acute Pancreatitis: If pancreatitis is suspected (severe persistent abdominal pain radiating to the back), discontinue Rybelsus immediately.
• • Diabetic Retinopathy Complications: Observed in patients with pre-existing diabetic retinopathy during rapid improvement in blood glucose control.
• • Hepatobiliary Disorders: Cholelithiasis (gallstones).

Symptoms:
Overdose with semaglutide may result in severe nausea, vomiting, and diarrhea, leading to dehydration.

Treatment:
No specific antidote exists. Supportive clinical management should be instituted considering the prolonged half-life of semaglutide (approximately 1 week).

Storage Requirements for Rybelsus 4 mg:

• 🌡️ Temperature: Store below 30°C.
• ☀️ Moisture & Light Protection: Store in original blister package to protect from moisture and light. Keep tablets in blister until time of administration.
• 👶 Safety: Keep out of reach of children.
• ⏳ Shelf Life: 24 months from manufacturing date. Rx Only.

To verify the authenticity of original Rybelsus 4 mg manufactured by Novo Nordisk, check the following packaging details:

• ✅ Novo Nordisk Logo: Distinctive corporate Apis bull logo printed on the front and side panel of the carton.
• ✅ Dosage Color Identification: 4 mg dose strength features a red/red-orange block accent on a white box with a yellow-orange side panel design.
• ✅ Typography: Product name "RYBELSUS" in bold dark blue font with registered trademark symbol ®.
• ✅ Batch Identification: Printed Lot Number, Manufacturing Date, and Expiration Date on the package side end flap.