Sucralfate - Uses, Dosage, and Adverse Reactions

Introduction:

Sucralfate is a short-term medication that directly works on the stomach lining and treats duodenal ulcers or stomach ulcers. The most significant advantage of Sucralfate is that it adheres to the ulcer site and prevents the recurrence of ulcers. However, an important point to be noted is that the drug does not prevent ulcers from occurring. Instead, it can help manage an active ulcer. Sucralfate's topical mechanism of action is that it forms a protective barrier, demonstrates anti-peptic effects, increases bicarbonate production, and promotes tissue growth, repair, and regeneration. In addition, Sucralfate is a safe medication because it does not get absorbed into the gastrointestinal system. Hence, the risk of side effects is minimal.

Developmental History and Approval Timeline of Sucralfate:

• Sucralfate, currently accepted globally as a non-systemic drug that prevents stomach ulcers, was introduced in Japan in 1968 as an ulcer-protecting agent.

• The drug was approved for medical use in the United States (US) in 1981.

• In 2019, Sucralfate was one of the most commonly prescribed drugs in the US.

• Finally, Sucralfate oral suspension was approved by the US FDA (Food and Drug Administration) on 16 December 1993 to manage active gastroduodenal ulcers.

How Does Sucralfate Works to Treat Peptic Ulcers?

Sucralfate is considered highly effective against gastric and duodenal ulcers as it binds to gastric and duodenal ulcers. In addition, it adheres to gastric erosions synthesized by ethanol and other anti-inflammatory drugs. The mechanism of action of Sucralfate is based on the fact that the drug gets attached to the defective mucosa and forms polyvalent bridges between the negatively charged ions of Sucralfate and positively charged ions of the proteins present within the mucosal lesions. In addition, the drug buffers acid absorbs bile salts, and blocks the action of pepsin.

Safety and Effectiveness of Sucralfate:

A placebo-controlled trial and Cimetidine and Ranitidine controlled studies were done to evaluate the safety and efficacy of Sucralfate in patients with gastric and duodenal ulcers. These trials have confirmed the efficacy of Sucralfate 1 gram (four times daily) in gastric and duodenal ulcers. The healing rates of the patients taking Sucralfate were in the range of 60 to 83 % after four weeks of treatment. However, the duodenal ulcer relapse rates are lower than those with Cimetidine therapy. Studies also report that Sucralfate and Cimetidine are equally effective in maintenance therapy. Sucralfate 1 gram taken in the morning can be tolerated well and effectively prevent gastric ulcer relapse. The trial results were miraculous because only two percent of patients presented with constipation.

For Patients:

What Are Gastric Ulcers?

Gastric ulcers or peptic ulcers are sores that form on the stomach lining. Although they mainly affect the stomach and small intestine, they can occur in any part of the gastrointestinal tract. Normally the stomach has a thick layer of mucus that protects it from the digestive juices. However, gastric ulcers arise when this layer is damaged. As a result, the digestive juice directly comes in contact with the stomach surface resulting in ulcers. Therefore, the ulcers must be cured at the earliest because they can become severe if left untreated for prolonged periods. The other causes of gastric ulcers can be Helicobacter pylori infection, prolonged use of nonsteroidal anti-inflammatory drugs like Ibuprofen, spicy foods, and stress.

What Are the Signs and Symptoms of Gastric Ulcers?

Sometimes the patient remains asymptomatic for prolonged periods due to ulcers. However, the signs and symptoms of gastric ulcers are listed below:

• Pain or burning sensation in the upper or middle part of the stomach.

• Nausea.

• Vomiting.

• Bloating.

• Heartburn.

• Persistent pain that might subside after taking antacids.

• Weight loss.

What Should the Patient Inform the Doctor Before Taking Sucralfate Tablets or Oral Suspension?

Before taking Sucralfate, the patient must inform the healthcare provider if he or she is:

• Allergic to Sucralfate or any of its ingredients. The patient can consult his doctor to know about the ingredients of Sucralfate tablets and oral suspension.

• Taking or has taken any over-the-counter drugs, prescription medicines, and herbal supplements. The patient must specifically mention if he is taking the following medications:

  • Anticoagulants or blood thinners.

  • Ciprofloxacin.

  • Digoxin.

  • Ketoconazole.

  • Levofloxacin.

  • Cimetidine.

  • Ranitidine.

  • Sparfloxacin.

  • Theophylline.

  • Tetracycline.

  • Nalidixic acid.

All the medications mentioned above must be taken two hours before taking Sucralfate. After that, the doctor might change the dosage of drugs and monitor the patients for adverse reactions.

• Take antacids. This is because they must be taken 30 minutes before taking Sucralfate.

• Diagnosed with diabetes, kidney disease, or other medical conditions that might interfere with swallowing and cause gag reflex or cough. The patient must inform the doctor if he has been diagnosed with gastrointestinal disorders or receiving enteral tube feedings.

• Pregnant or planning to conceive or breastfeeding in the long term. The doctor might modify the dose of the drug.

What Are Some of the Side Effects of Sucralfate Tablets and Oral Suspension?

Side effects are always associated with medications. However, some patients might not have them commonly. Some of the side effects of Sucralfate tablets and oral suspension are:

• Constipation.

• Backache.

• Dizziness or lightheadedness.

• Diarrhea.

• Headache.

• Hives.

• Skin rashes.

• Itching.

• Sleepiness.

• Stomach cramps.

• Indigestion.

Some of the rare side effects of Sucralfate tablets and oral suspension are listed below:

• Bluish discoloration of the lips and fingernails.

• Chest pain.

• Cough.

• Dry mouth.

• Dry skin.

• Flushing.

• Increased precipitation, hunger, and thirst.

• Nausea.

• Pale skin.

• Irregular breathing.

• Stomach ache.

• Chest tightness.

What Are the Medical Uses of Sucralfate?

Sucralfate is predominantly used to manage duodenal ulcers unrelated to nonsteroidal anti-inflammatory drugs (NSAIDs). The drug is widely used owing to its efficacy and safety. Sucralfate is commonly used for the following:

1. Active gastric or duodenal ulcers.

2. Maintenance therapy for ulcers that have already subsided.

3. It is used as a part of triple combination therapy with Lansoprazole and Cisapride to improve the symptoms and quality of life.

4. Stomatitis or aphthous ulcers due to chemotherapy or radiation therapy.

5. Sucralfate is the first line of therapy for gastroesophageal disorder (GERD) in pregnancy, along with lifestyle changes.

6. It is used in the prevention of stress-induced ulcers.

7. Prevents the formation of strictures and corrosive burns.

8. It is used to treat rectal bleeding due to radiation therapy.

9. Sucralfate suspension is used before surgeries related to the esophagus.

10. It can be used as a protection against ventilator pneumonia.

How Should the Patient Take the Drug?

Sucralfate is available in the form of tablets and oral solutions. If the patient is planning to consume the drug for stomach ulcers, the oral solution or the tablets are usually taken four times daily. However, if the patient plans to prevent the recurrence of ulcers, the tablets are usually taken twice daily. Sucralfate must always be taken on empty, meaning one or two hours before meals. Consume the drug at the same time daily. The patient must follow all the instructions on the prescription label carefully. One can also consult the doctor in case of confusion regarding the dosage instructions. Do not consume the drug excessively, and take only the prescribed amount.

For Doctors:

Sucralfate Tablets and Suspension:

Description:

Sucralfate tablets and suspension Sucralfate is an alpha-D-glucopyranoside, beta-D fructofuranosyl-, octakis-(hydrogen sulfate), and aluminum complex. The suspension is meant for oral suspension and contains 1 gram of Sucralfate per 10 mL.

Composition of Sucralfate Suspension - Colloidal silicon dioxide, water USP, microcrystalline cellulose, methylcellulose USP, purified glycerin USP, simethicone USP, and sorbitol solution USP, and methylparaben.

Composition of Sucralfate Tablets - D and C Red #30 Lake, FD&C Blue #1 Lake, microcrystalline, magnesium stearate, cellulose, and starch.

Indications and Usage:

• Sucralfate tablets and oral suspension are used as a short-term treatment (up to eight weeks) for active or recurring gastroduodenal ulcers. After taking the Sucralfate tablets or oral suspension, the healing occurs during the first or second week. However, the patient must continue taking the drug for four to eight weeks until the X-ray and other investigations have demonstrated complete healing.

• Sucralfate tablets can also be used as maintenance therapy for patients with duodenal ulcers after healing.

• Sucralfate also lowers the intensity and frequency of dyspeptic symptoms associated with NSAID therapy.

• The drug is also used to manage numerous epithelial wounds listed below:

  • Inflammatory dermatitis (inflammatory reaction of the skin).

  • Ulcers.

  • Mucositis (inflammation and soreness of the gut).

  • Burn wounds.

• Sucralfate also protects the intestinal tract from ulcers related to diversion colitis (a non-specific disorder that mainly affects the rectum and intestine).

Contraindications:

Side effects or adverse reactions are associated with every medication. Similarly, Sucralfate is absolutely and relatively contraindicated under specific circumstances. The drug is absolutely contraindicated in hypersensitivity patients to avoid the risk of an anaphylactic reaction. Sucralfate is a pregnancy category B drug, so nothing has been known about its safety in the pregnant population. The drug is relatively contraindicated under the following conditions:

1. End-stage renal disease.

2. Uncontrolled diabetes.

3. Gag reflex.

4. Impaired swallowing.

Clinical Pharmacology:

The most significant advantage of Sucralfate is that it is absorbed in only small quantities from the gastrointestinal tract. However, sulfated disaccharides are absorbed in small amounts and excreted rapidly in the urine. The mechanism by which Sucralfate accelerates the healing of duodenal ulcers remains undetected. It has not been known whether the drug exerts its effects through systemic or local action. Some of the observations from the studies are listed below:

• Studies report that Sucralfate develops an ulcer adherent complex with the proteinaceous exudate at the site of the ulcer.

• During the in vitro studies, it was observed that a Sucralfate albumin film provides a barrier to the entry of hydrogen ions.

• If Sucralfate is given as per the recommended dosage, it reduces pepsin activity in gastric juice by 32 %.

Observations from the above studies suggest that Sucralfate's antiulcer properties are due to the formation of an ulcer-adherent complex. This is because the complex protects the site against further acid attacks.

Additional Points on the Clinical Pharmacology of Sucralfate:

• The time of onset of the drug is one to two hours.

• When Sucralfate is administered orally, five percent of it gets absorbed.

• It is considered a non-systemic drug.

• Sucralfate is excreted unaltered in the urine and does not undergo systemic metabolism.

Dosage and Administration:

Sucralfate Oral Suspension and Tablets:

Active Duodenal Ulcer or Gastric Ulcers:

The recommended dosage of Sucralfate for adults with duodenal ulcers is 1 gram (10 mL per two teaspoons) four times daily. The patient must take the drug on an empty stomach. Some patients might require antacids. However, they must be administered half to one hour before or after Sucralfate.

Elderly Population - The doctor must carefully select the dose for elderly patients. They must be given a low dose initially to reduce the risk of renal, hepatic, and cardiac disorders or other concomitant diseases.

Maintenance Therapy - The recommended dosage of Sucralfate tablets for maintenance therapy is 1 gram daily.

How Is Sucralfate Supplied?

Sucralfate Suspension:

Sucralfate suspension 1 gram per 10 mL is supplied as a pink-colored solution in a bottle of 14 fl oz.

Sucralfate Tablets:

The tablets are light pink colored, oblong, scored, and supplied in bottles. They are embossed with the drug name on one side and 1712 on the other.

Adverse Reactions of Sucralfate Tablets and Suspension:

• Diarrhea.

• Dry mount.

• Flatulence.

• Gastric discomfort.

• Nausea.

• Vomiting.

• Indigestion.

• Rashes.

• Pruritus.

• Insomnia.

• Sleepiness.

• Vertigo.

• Dizziness.

• Anaphylactic reactions.

• Dyspnea.

• Swelling of the lips and mouth.

• Pharyngeal edema.

• Bronchospasm.

• Laryngeal edema.

• Edema of the respiratory tract.

• Delayed gastric emptying.

• The inadvertent injection can cause cerebral and pulmonary emboli.

• Delayed gastric emptying.

Overdosage:

No specific treatment recommendations can be given for Sucralfate overdose because of the limited studies available in humans. However, Sucralfate 12 grams per kg was administered in animals, but nothing could be known about the lethal dose. The chances of overdose are less because Sucralfate is absorbed in fewer quantities from the gastrointestinal tract. Hence, the risks associated with Sucralfate overdose are less. Some patients remain asymptomatic, while some experience abdominal pain, nausea, vomiting, and dyspepsia.

Carcinogenesis, Mutagenesis, and Impairment of Fertility:

Oral toxicity studies were conducted for 24 months in mice at doses 12 times the human dose. However, no evidence of toxicity was noted. In addition, the drug was administered in animals at a dose 38 times higher than the normal dose. However, no clinically significant changes in fertility were noted. Nothing has been known about the mutagenicity of the drug.

Drug Interactions:

The following drugs reduce the bioavailability or the extent of absorption of Sucralfate:

• Cimetidine.

• Digoxin.

• Fluoroquinolones.

• Ketoconazole.

• Phenytoin.

• Ranitidine.

• Quinidine.

• Theophylline.

• Tetracycline.

• Warfarin therapy.

Use in Specific Populations:

Patients With Chronic Renal Failure and on Dialysis:

Patients taking Sucralfate orally often present with elevated aluminum levels. This is because aluminum is absorbed in small amounts from the gastrointestinal tract. Hence, if the drug is used concomitantly with other aluminum-containing antacids, the total aluminum levels of the body increases. Normally, aluminum is expelled from the body in the urine. However, patients with renal failure fail to do so and retain aluminum within the body. Patients on dialysis also find it difficult to expel aluminum because it remains bound to the transferrin proteins and does not cross the dialysis membrane. Hence, such patients must remain careful as they are at a higher risk of aluminum toxicity.

Pregnancy:

Sucralfate is a pregnancy category B drug. Several studies have been done in animals to evaluate the teratogenic potential of the drug. However, the drug did not cause any harm. Unfortunately, not much data is available regarding the teratogenic potential of the drug in the human population. Hence, Sucralfate must only be administered to pregnant females after calculating the risk-benefit ratio.

Lactating Mothers:

It is not known whether the drug can pass in human milk. However, lactating mothers must be cautious while taking Sucralfate.

Pediatric Population:

Nothing has been known about the safety and effectiveness of Sucralfate in children.

Geriatric Use:

Not much information is available regarding the effectiveness of Sucralfate in the geriatric population because a sufficient number of patients above 65 were not included in the trial. Therefore, the dose must be selected carefully for elderly patients and should be given a low dose initially. In addition, such patients must be monitored carefully for renal dysfunction and other side effects.

Clinical Trials:

A multicenter double-blind and a placebo-controlled trial was done on patients to evaluate the effectiveness of Sucralfate suspension. The dosage administered was 1 gram (10 mL) four times daily. The patients demonstrated healing rates of 16 % in the second week, 46 % in the fourth week, and 66 % in the eighth week. In addition, a placebo-controlled trial was done on 600 patients who took the Sucralfate tablet for four weeks. These patients presented an overall healing rate of 92 % during the trial.