Semaglutide / Cyanocobalamin Injection

Semaglutide

Semaglutide is a synthetic glucagon-like peptide-1 receptor agonist (GLP-1 RA) that belongs to a class of antidiabetic agents called incretin mimetics. Incretins are endogenous compounds, including glucagon-like peptide-1 (GLP-1), that improve glycemic control once released into the circulation via the gut.

Cyanocobalamin

Cyanocobalamin is a vitamin of the B-complex family, commonly known as cobalamin (corrinoids). It is a synthetic or man-made form of vitamin B12 that is available as both a prescription and over-the-counter (OTC) medication. Cobalamins exist in several other chemical forms, including hydroxocobalamin, methylcobalamin, and adenosylcobalamin. It contains a cyano (cyanide) group in its structure, which makes it more stable than other forms of vitamin B12 as the cyanide stabilizes the molecule from deterioration.

The chemical structure of cyanocobalamin contains the rare mineral cobalt (4.34%), which binds the cyano group and is located in the center of a corrin ring. Compared to other forms of vitamin B12, it is easier to crystallize and more air-stable. Cyanocobalamin is usually obtained as a dark red, amorphous, or crystalline powder, orthorhombic needles, or red crystals. The anhydrous form of the compound is highly hygroscopic. It may absorb up to 12% of water if exposed to air. Cyanocobalamin is sparingly soluble in alcohol and water (1 in 80 of water), but insoluble in chloroform, acetone, and ether. The coenzymes of this vitamin are highly unstable in light.

Cyanocobalamin is available in several dosage forms including tablets, nasal spray, and injection.

The lack of vitamin B12 may result from any of the following conditions:

Malabsorption - impaired absorption of vitamin B12

Diphyllobothrium latum and related species (the fish tapeworm) infestation - these parasites compete with vitamin B12 for intestinal absorption; this leads to malabsorption of the vitamin

Malignancy of the pancreas or bowel

Folic acid deficiency

Semaglutide

Semaglutide is an incretin mimetic; specifically, semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist with 94% sequence homology to human GLP-1. Semaglutide binds and activates the GLP-1 receptor. GLP-1 is an important gut-derived glucose-lowering hormone. GLP-1 enhances insulin secretion; it increases glucose-dependent insulin synthesis and in vivo secretion of insulin from pancreatic beta cells in the presence of elevated glucose.

In addition to increases in insulin secretion and synthesis, GLP-1 suppresses glucagon secretion, slows gastric emptying, reduces food intake, and promotes beta-cell proliferation. The principal mechanism of protraction resulting in the long half-life of semaglutide is albumin binding, which results in decreased renal clearance and protection from metabolic degradation; semaglutide is stabilized against degradation by the DPP-4 enzyme.

Semaglutide reduces blood glucose through a mechanism where it stimulates insulin secretion and lowers glucagon secretion, both in a glucose-dependent manner. Therefore, when blood glucose is high, insulin secretion is stimulated and glucagon secretion is inhibited. The mechanism of blood glucose lowering also involves a minor delay in gastric emptying in the early postprandial phase.

Cyanocobalamin

Cyanocobalamin is a vital compound for cell division and growth, hematopoiesis, and nucleoprotein and myelin synthesis. This vitamin also has an important role in protein synthesis, neural metabolism, DNA and RNA production, as well as fat and carbohydrate metabolism.

Cyanocobalamin binds itself to plasma proteins in the systemic circulation. It attaches with specific cobalamin binding proteins, called transcobalamin I and II, to enter into the tissues. In cells, this vitamin functions as a cofactor for two vital enzymatic reactions: (1) methionine synthase, i.e. the regeneration of methionine from homocysteine, and (2) methylmalonyl-CoA mutase, i.e. the isomerization of methylmalonyl-CoA to succinyl-CoA. Both these methylation reactions are vital for growth and cell reproduction.

Methionine, a sulfur-containing, essential amino acid, is a precursor of S-adenosylmethionine, a cofactor for one-carbon metabolism and the final methyl donor for the methylation of DNA, RNA, proteins, and phospholipids. On the other hand, the methylmalonyl-CoA mutase helps to metabolize odd-chain fatty acids and branch-chain amino acids. SH groups activate many enzyme systems involved in protein synthesis as well as fat and carbohydrate metabolism.

Semaglutide

Semaglutide should not be used in individuals with known hypersensitivity to the drug. Reactions such as angioedema, anaphylaxis, or other serious allergic responses may occur and require immediate medical attention and discontinuation of treatment.

This medication is also not appropriate for individuals with a personal or family history of certain thyroid conditions, including thyroid C-cell tumors or syndromes such as multiple endocrine neoplasia type 2. Patients should be aware of symptoms like a lump in the neck, difficulty swallowing or breathing, or persistent hoarseness.

Semaglutide is not indicated for use in type 1 diabetes.

Patients beginning semaglutide treatment should monitor for signs of low blood sugar, especially when used in combination with medications like insulin or sulfonylureas. Adjustments to these medications may be necessary. Warning signs of hypoglycemia can sometimes be subtle, particularly in long-standing diabetes or among elderly individuals. Preparedness with a source of fast-acting glucose is recommended.

Pancreatitis has been reported with the use of this drug class. Patients should be attentive to symptoms like severe, persistent abdominal pain and seek medical care promptly if these occur.

Semaglutide may affect gallbladder function. Symptoms such as abdominal pain, fever, or nausea may require evaluation for gallbladder disease. Rapid weight loss can increase the likelihood of gallstones.
Changes in vision should be reported promptly, especially for patients with a history of diabetic retinopathy, as semaglutide may impact the progression of this condition.

Patients with reduced kidney function should use semaglutide cautiously. Dehydration from side effects like nausea or vomiting can worsen kidney function, and supportive care may be required.
Those with a history of depression or suicidal thoughts should be monitored closely during treatment. Mood changes or concerning behavior should be reported immediately.

Semaglutide is not recommended during pregnancy or breastfeeding. It should be discontinued at least two months prior to a planned pregnancy. An alternative form of diabetes or weight management should be considered during these periods.

Use in older adults should be approached with care, particularly due to increased sensitivity to hypoglycemia. Treatment plans may require adjustment to prevent complications.

Cyanocobalamin

Cyanocobalamin should not be used in individuals with known allergies to cobalt or vitamin B12. Hypersensitivity reactions, including severe allergic responses, may occur.

Caution is advised when administering cyanocobalamin to individuals with early Leber’s disease, severe anemia, or kidney dysfunction. Premature infants and neonates should not receive formulations containing certain preservatives.

Before starting treatment, a full assessment of vitamin B12 status, iron, folate, and blood counts is important. These parameters should be monitored throughout treatment to ensure proper response and prevent complications such as hypokalemia or abnormal platelet counts.

Patients with vitamin B12 deficiency may have an increased risk of certain gastrointestinal conditions. Ongoing monitoring and evaluation are essential to guide effective treatment.

Various factors can reduce the effectiveness of cyanocobalamin therapy, including older age, certain infections, medical conditions, or interactions with other medications. These should be considered when managing therapy and monitoring patient response.

Semaglutide

Semaglutide may cause low blood sugar, particularly when used in combination with insulin or sulfonylureas. The risk of hypoglycemia increases with these combinations and should be carefully monitored. Symptoms of low blood sugar can include shakiness, sweating, confusion, and dizziness. Severe episodes may require assistance from another person.

Gastrointestinal side effects are the most commonly reported with semaglutide. These include nausea, vomiting, diarrhea, abdominal discomfort, constipation, decreased appetite, indigestion, gas, and bloating. These effects are more likely to occur during dose escalation and are a common reason for discontinuing treatment. Rarely, inflammation of the appendix has also been reported.

Semaglutide may be associated with gallbladder issues, such as gallstones or gallbladder inflammation. These events can occur during weight loss, particularly if the weight loss is rapid. Signs include abdominal pain, nausea, or digestive disturbances.

Fatigue, headache, dizziness, and taste disturbances have been observed with semaglutide use. Some patients may experience discomfort or irritation at the injection site.

In some individuals, the immune system may produce antibodies against semaglutide. In rare cases, these antibodies may interact with natural hormones in the body. The impact of these antibodies is unclear.

Changes in kidney function have been reported, especially in those who experience dehydration from gastrointestinal side effects. Monitoring of kidney function is recommended during treatment, particularly during dose adjustments.

Increases in pancreatic enzymes such as amylase and lipase have been observed. Pancreatitis has occurred in some patients. Symptoms include persistent and severe abdominal pain, which may radiate to the back and be accompanied by nausea or vomiting. Patients with a history of pancreatitis should use semaglutide with caution.

Allergic reactions, including serious ones such as anaphylaxis, angioedema, and skin reactions, have occurred with semaglutide use. Any signs of an allergic reaction should prompt immediate discontinuation and medical evaluation.

Semaglutide may cause an increase in resting heart rate. Patients should be advised to report symptoms like palpitations or a racing heart. In some cases, semaglutide may need to be discontinued.

Low blood pressure and fainting may occur, particularly in those also taking antihypertensive medications. This is often related to volume loss from gastrointestinal side effects.

In people with diabetes and pre-existing eye disease, rapid improvement in blood sugar control may temporarily worsen diabetic retinopathy. Patients with a history of diabetic eye disease should be observed for changes during treatment.

Semaglutide may carry a risk of thyroid-related tumors. Symptoms such as a lump in the neck, hoarseness, or trouble swallowing or breathing should be reported. Patients with a history of certain thyroid conditions should avoid using semaglutide.

Cyanocobalamin

Cyanocobalamin is generally well tolerated, even at high doses. However, some individuals may experience side effects following injection.

Rare but serious allergic reactions, including anaphylaxis, can occur.

Cardiovascular effects may include fluid buildup in the lungs, heart strain during early treatment, or rare vascular issues.

Blood-related effects may include an increase in red blood cells in certain conditions.

Digestive side effects may include mild diarrhea.

Skin reactions such as itching or rash may occur.

Some individuals may report a general sense of swelling or discomfort.

Semaglutide

Semaglutide should not be used during pregnancy for the treatment of obesity or weight management. Individuals of childbearing potential should use effective contraception during treatment and discontinue semaglutide immediately if pregnancy occurs.

Use should be avoided unless the expected benefits outweigh the potential risks to the fetus. Animal studies have shown that semaglutide can affect fetal development and pregnancy outcomes. Additionally, salcaprozate sodium (SNAC), an absorption enhancer in oral semaglutide tablets, has been shown to cross the placenta in animal studies and may accumulate in fetal tissues.

Cyanocobalamin

There is no adequate data from controlled human studies regarding the use of cyanocobalamin during pregnancy. However, the body’s demand for vitamin B12 increases during pregnancy, and this compound is considered necessary for healthy fetal development.

When deficiency is present, cyanocobalamin should be used if the anticipated benefit to the patient outweighs any potential risk to the fetus.

Semaglutide

Use injectable semaglutide with caution during breastfeeding. Oral semaglutide tablets are not recommended for use while nursing due to uncertainty about their safety in infants. The drug and its absorption enhancer may pass into breast milk and accumulate in the infant, particularly in newborns and young infants with underdeveloped metabolic pathways. Because of the potential for adverse effects in the breastfed child, oral formulations should be avoided during lactation.

If semaglutide is discontinued while breastfeeding and blood glucose is not adequately controlled with diet and exercise alone, alternative therapies such as insulin or other oral medications may be considered. When oral blood sugar-lowering medications are used during breastfeeding, the infant should be monitored for signs of low blood sugar, such as unusual drowsiness or irritability.

Cyanocobalamin

Cyanocobalamin passes into breast milk at levels that reflect maternal blood concentrations. It is considered compatible with breastfeeding when taken in standard amounts. No adverse effects have been observed with typical daily intake of vitamin B12 during lactation.

Upon receipt of medication, immediately store between 35°F to 46°F (2°C – 8°C). Keep all medicines out of the reach of children. Throw away any unused medicine within 29 days of puncture or the BUD, which ever comes first. Do not flush unused medications or pour down a sink or drain.