Sevelamer Carbonate - Dosage, Indications, Contraindications, and Administration

Overview

Sevelamer carbonate is a pharmaceutical phosphate amine created as an alternative to sevelamer hydrochloride. It is a polymeric structure with an anion exchange resin, and it is chemically known as poly(allylamine-co-N, N Diallyl-1,3 diamino-2-hydroxyproline). The drug is insoluble in water but is hygroscopic. Sevelamer carbonate is a film-coated tablet for oral administration and is used to treat hyperphosphatemia in CKD (chronic kidney disorders) patients on peritoneal dialysis. The drug was approved by Food and Drugs Administration on 30th October 1998 and is manufactured by Winthrop US, a Sanofi company.

Uses of Sevelamer Carbonate

Sevelamer carbonate is indicated for oral administration to control hyperphosphatemia or high serum phosphorous levels in children (six years and above) and adults suffering from chronic kidney disorders (CKD) on dialysis.

Dosage and Administration

Starting Dose:

The recommended dose for Sevelamer carbonate is 2.4 or 4.8 grams daily, over three meals per day, depending on a person's clinical needs and serum phosphorus levels.

Warnings and Precautions

• Intestinal Obstruction and Ileus: Cases managed with Sevelamer carbonate (tablets/capsules) have experienced intestinal obstruction and ileus or subileus. Constipation may also occur; therefore, a person should be carefully monitored while giving the treatment with Sevelamer carbonate. Careful evaluation should be done for patients developing severe constipation and other gastrointestinal disorders or symptoms.

• Hypercalcemia or Hypocalcemia: Sevelamer carbonate does not contain calcium. However, patients may develop hypocalcemia or hypercalcemia and should be monitored regularly for calcium levels. Supplement of elemental calcium can be prescribed if needed.

• Peritonitis: Dialysis patients are more prone to certain infections, and peritonitis due to peritoneal dialysis is one of the major complications in such patients. Therefore, symptoms in patients receiving peritoneal dialysis should be carefully managed with proper aseptic technique.

• Metabolic Acidosis: Patients with chronic kidney disorder (CKD) are more prone to develop metabolic acidosis. Therefore, monitoring serum bicarbonate levels is recommended.

• Folate Deficiency and Fat-soluble Vitamins: Sevelamer carbonate can bind to fat-soluble vitamins in the food. However, sometimes due to the severity of the condition and lack of dietary intake, low levels of fat-soluble vitamins A, D, E, and K can occur in CKD patients. Therefore, a patient managed with Sevelamer carbonate, not taking supplemental vitamins, should be carefully monitored. It is recommended that CKD patients not on dialysis should be given vitamin D supplements along with Sevelamer carbonate. For peritoneal dialysis patients, folic acid and fat-soluble vitamins are recommended.

• Hypothyroidism: CKD patients co-administered with Levothyroxine and Sevelamer carbonate should be monitored closely.

• Swallowing and Choking Difficulties: Many patients may have comorbid conditions, esophageal abnormalities, and swallowing difficulties. Such patients should be carefully monitored for swallowing difficulty and can be given powdered Sevelamer carbonate.

• Inflammatory Gastrointestinal Disorders: Sevelamer carbonate has also caused severe complications associated with gastrointestinal tract disorders. These include inflammatory disorders such as perforations, necrosis, hemorrhage ulcerations, colitis, etc. Therefore, patients developing severe gastrointestinal symptoms with Sevelamer carbonate should be carefully monitored.

• Hyperparathyroidism: This condition cannot be treated with Sevelamer carbonate. However, patients can manage secondary hyperthyroidism with Sevelamer carbonate and other therapeutic approaches, such as calcium supplements.

• Excipient Drugs: Lactose monohydrate is present in Sevelamer carbonate; therefore, it is not recommended in patients with hereditary problems such as glucose-galactose malabsorption or galactose intolerance.

Use in Specific Populations

• Pediatric Use: Sevelamer carbonate is not recommended in children below the age of six years or having a body surface area (BSA) below 0.7 square meters. The efficacy and safety of the drug are recommended only in children above six years and having more than 0.7 square meters BSA. Also, oral suspension of Sevelamer carbonate is available for this population instead of tablets.

• Geriatric Use: No specific-geriatric problems that may limit its use in this population is documented. However, various complications can occur in CKD patients during treatment with Sevelamer carbonate. Therefore, precautions must be taken carefully.

For Patients:

What Is Hyperphosphatemia?

Hyperphosphatemia condition arises when there is too much phosphate in the blood. This may occur due to various conditions such as hypoparathyroidism, advanced chronic kidney disease, and respiratory and metabolic acidosis. Hyperphosphatemia does not cause symptoms but can lead to hypocalcemia (removal of calcium from blood and bones) and cause various symptoms. Hyperphosphatemia can be managed with dietary changes, medications, and dialysis.

What Is Sevelamer Carbonate?

Sevelamer carbonate is a pharmaceutical drug used to treat hyperphosphatemia in patients on dialysis due to chronic kidney disease (CKD). Phosphate gets eliminated through dialysis, but it cannot remove enough to maintain the balance. Low blood phosphate levels help reduce the risk of cardiac diseases and keep bones strong. Therefore, Sevelamer carbonate helps to hold onto phosphate in the diet so it can be eliminated from the body.

How To Use Sevelamer Carbonate?

Sevelamer carbonate can be taken directly through the mouth as prescribed by the doctor or thrice a day with a meal. The medicine should not be crushed or chewed and should be swallowed. The dosage is per the patient's medical condition and phosphate levels in the body. In children, the dosage is decided according to the body size.

If the drug is used in powdered form, check the manufacturing directions on the package for mixing with water or food. Use appropriate water to mix the dose and stir well before drinking to avoid the dose sticking to the bottom of the container. If the dose is recommended to be taken with food, do not add it to heated food. Be careful to take the dose three times a day or as prescribed by the doctor.

What Special Precautions Should Be Taken?

• Allergies: The patient should inform the doctor about their allergies to any medication before taking Sevelamer carbonate. The drug contains few ingredients that can cause inflammatory and allergic reactions. Therefore, doctors should be informed before the treatment starts.

• Medical History: Inform the doctor about a person's medical condition, such as:

• Dysphagia (swallowing problems).

• Stomach and intestinal problems like constipation, colitis, and blockage.

• Low blood phosphorous levels.

• Drug History: Inform the doctor about any non-prescription drugs, prescription drugs, and herbal products that a person is taking.

Pregnancy and Breastfeeding

Sevelamer carbonate should be prescribed in pregnancy only when its need is indicated. The drug's associated risks and benefits should be discussed with the doctor before taking this medication. In addition, the contraindication for this drug during breastfeeding is still unknown; therefore, consult the doctor before taking Sevelamer carbonate.

Side Effects of Sevelamer Carbonate

Sevelamer carbonate tablets or capsules can cause various side effects. Therefore, a person should consult the doctor if they experience the following symptoms:

• Diarrhea.

• Nausea.

• Vomiting.

• Stomach upset.

• Cough.

• Constipation.

• Gas.

The side effects can also be very severe sometimes and need immediate medical attention. These include:

• Severe constipation.

• Problems with bowel movement.

• Stomach or intestinal bleeding and ulcers, including abdominal pain, bloody stool, vomiting, and dizziness.

• Breathing difficulties.

• Chest pain.

• Swelling, redness, and pain in lower legs.

Severe allergic reactions are uncommon with Sevelamer carbonate, but if a person experiences rash, itching, or any other allergic reaction, consult the doctor immediately.

Storage and Disposal

Sevelamer carbonate is stored away from moisture and light at room temperature. Store the drug away from children and discard it safely when it is no longer needed or expires.

What Should Be Done in Case of a Drug Overdose and Missed a Dose?

In case of overdose from Sevelamer carbonate,contact the poison control helpline immediately.

If a person misses out on a dose, skip it unless they eat something. Also, skip the missed dose to avoid a double dose if it is time for the next dose. Instead, take doses at regular intervals.

For Doctors:

Indications

• Sevelamer carbonate is recommended in adult patients receiving peritoneal dialysis or hemodialysis to control hyperphosphatemia.

• Sevelamer carbonate is also recommended in adult patients suffering from CKD (chronic kidney disorder) who are not receiving dialysis to treat hyperphosphatemia.

Pharmacology

Mechanism of Action:

Sevelamer carbonate is a non-absorbed phosphate-binding cross-linked polymer free of calcium and metal. It is separated by one carbon from the polymer backbone and contains multiple amines. Sevelamer carbonate interacts through hydrogen and ionic binding with the phosphate molecules. Therefore, it lowers the phosphate levels in the serum by binding to the phosphate in the GI (gastrointestinal tract) and decreasing its absorption.

Pharmacodynamics:

In addition to lowering the concentration of serum phosphate levels in the body, Sevelamer carbonate may also interfere with the absorption of fat by binding to the bile acids and thus causes a reduction in the absorption of various fat-soluble vitamins such as A, D, and K. Clinical trials have shown the decline of total and the mean LDL cholesterol levels up to 15 to 31 percent. However, no effects were seen on albumin, HDL cholesterol, and triglycerides.

Pharmacokinetics:

The absorption study conducted in healthy volunteers has suggested and confirmed that Sevelamer carbonate is not absorbed in the gastrointestinal tract. Also, no evidence of the accumulation of the drug has been found so far in a one-year clinical trial. However, the absorption and accumulation of Sevelamer carbonate cannot be excluded, which may occur from long-term chronic treatment with the drug.

Ingredients:

Active Ingredients:

Sevelamer carbonate is a polymeric amine that can bind with phosphate and is used for oral administration as an active ingredient. The table form contains 800 mg of Sevelamer carbonate on an anhydrous basis, whereas the powdered form contains 0.8 g to 2.4 g of Sevelamer carbonate.

Inactive Ingredients:

Inactive ingredients in tablet form are Diacetylated monoglycerides, hypromellose, microcrystalline cellulose, zinc stearate, and sodium chloride. In addition, the imprints of the tablet contain black ink of iron oxide. Inactive ingredients in powdered form are artificial and natural citrus flavors, sodium chloride, propylene glycol alginate, ferric oxide (yellow), and sucralose.

Warning and Precautions:

The safety and efficacy of Sevelamer carbonate in adult patients with chronic kidney disorder (CKD), not on dialysis, and having serum phosphate levels < 1.78mmol/liter has not been established. Therefore, Sevelamer carbonate is not recommended in such patients. The safety and efficacy of Sevelamer carbonate are also not established in the following medical conditions:

• Active inflammatory bowel disease.

• Dysphagia.

• Gastrointestinal tract surgery.

• Swallowing disorders.

• Severe gastrointestinal disorders include irregular bowel movement, gastroparesis, and retention of gastric content.

Therefore, treatment with Sevelamer carbonate should be carefully monitored and re-evaluated in patients suffering from these conditions.

Dosage and Forms

• Tablets: 800 g.

• Powder: 0.8 g and 2.4 g packet.

Administration of the Drug

Sevelamer carbonate is for oral use. The starting dose is 0.8 or 1.6 g orally daily with three meals.

• For serum phosphorous levels- 1.78 to 2.42 mmol/l

2.4 g per day over three meals.

• Serum phosphorous levels- >2.42 mmol/l.

4.8 g per day over three meals.

Consideration for Administration

Titration and Maintenance

Serum phosphorus levels are monitored regularly. The recommended dose of Sevelamer carbonate is titrated by 0.8 grams three times per day. The increment is done every two to four weeks to achieve the accepted serum phosphorus levels. Therefore, the daily dose of Sevelamer carbonate should be approximately 6 grams per day along with the prescribed diet.

The treatment with Sevelamer carbonate is based on the patients' requirement to control serum phosphate levels. The daily dose of Sevelamer carbonate should be approximately 6 grams per day.

Contraindications

Sevelamer carbonate is contraindicated in the following conditions:

• Bowel obstruction.

• Hypophosphatemia (low phosphate levels in the body can be further decreased by Sevelamer carbonate).

• Hypersensitivity to the active ingredient.

Adverse Effects

The adverse effects caused by Sevelamer carbonate are of mild to moderate intensity and were found to cause adverse effects in the gastrointestinal system. The adverse effects included:

• Nausea.

• Vomiting.

• Diarrhea.

• Constipation.

• Abdominal pain.

• Upper abdominal pain.

• Hypersensitivity.

• Intestinal obstruction.

• Gastrointestinal necrosis and hemorrhage.

• Skin rash.

• Pruritus.

• Intestinal ulceration and perforation.

Drug Interactions

Sevelamer carbonate interacts with the following drugs:

• Ciprofloxacin: Sevelamer carbonate decreases almost 50 % of the bioavailability of Ciprofloxacin when co-administered. Therefore, sevelamer carbonate should be taken along with Ciprofloxacin.

• Levothyroxine: Monitoring is recommended in patients for TSH (thyroid stimulating hormone) if they take Levothyroxine and Sevelamer carbonate. Rare cases of hypothyroidism have been reported with the co-administration of Levothyroxine and Sevelamer carbonate.

• Proton-pump Inhibitors: Sevelamer carbonate taken along with proton-pump inhibitors may cause an increase in phosphate levels. Therefore, the drug should be cautiously prescribed with proton-pump inhibitors, and the patient should be carefully monitored for phosphate serum levels.

• Digoxin, Warfarin, Enalapril, and Metoprolol: The interaction of Sevelamer carbonate does not affect the bioavailability of drugs such as Digoxin, Warfarin, Enalapril, and Metoprolol.

• Anti-seizure and Anti-arrhythmic: These drugs are used to treat seizures and arrhythmia but were excluded from clinical trials, but the reduction in absorption could not be eliminated. Anti-arrhythmic should be taken at least three hours after or one hour before Sevelamer carbonate. Blood monitoring is recommended after that.

Toxicity

No clinical data reveal any specific toxicity or hazard, such as genotoxicity or repeated dose toxicity with Sevelamer carbonate in humans. Therefore, the risk of systemic toxicity caused by Sevelamer carbonate is very low.