Vancomycin Hydrochloride - Dosage, Administration, Indications, Contraindications, Side Effects, Special Considerations, Warnings, and Precautions

Overview:

Vancomycin is an antibiotic that fights bacteria in the intestines. It is used for intestinal infections caused by Clostridium difficile or staphylococcus bacteria affecting the colon and small intestines. It is taken orally and primarily works in the intestines without entering the rest of the body. It would not treat infections elsewhere; there is an injectable form. Vancomycin hydrochloride is a Food and Drug Administration (FDA)-approved antibiotic for treating bacterial infections, including those caused by Clostridium difficile and Staphylococcus aureus. These bacteria can lead to infections in people with weakened immune systems, such as those with HIV (human immunodeficiency virus).

Drug Group:

Vancomycin is a medication that helps treat inflammation in the intestine caused by specific bacteria. This medication kills bacteria by disrupting their cell wall formation. It is part of a group of medicines known as glycopeptide antibiotics.

Available Doses and Dosage Forms:

Available Doses:

• Clostridium Difficile-Associated Diarrhea: The usual dose is 125 milligrams (mg) taken by mouth four times a day for ten days.

• Enterocolitis: The dose can range from 500 mg to two grams taken by mouth daily, divided into three to four doses. The maximum daily dose should not exceed two grams, and the treatment duration is typically seven to ten days.

• These medications do not work if given by injection.

Dosage Forms:

• Each kit contains Vancomycin hydrochloride in a powder form.

• The powder can be mixed with a grape-flavored diluent to create an oral solution.

• The kit is available in different strengths, containing either 3.75 grams (g), 7.5 g, or 15 g of Vancomycin.

For Patients:

What Is Clostridium Difficile-Associated Diarrhea?

Clostridium difficile, or C. diff, is a harmful bacterium that can lead to severe diarrhea, often as a side effect of taking antibiotics. It commonly affects older individuals in medical settings, especially those on antibiotics. Symptoms like diarrhea, fever, stomach discomfort, and loss of appetite can appear shortly after antibiotic use. C. diff can be contagious and spread from one person to another.

How Does Vancomycin Hydrochloride Work?

Vancomycin is given as an IV injection, slowly over at least 60 minutes. A person might have side effects like dizziness or itching, so tell the doctor immediately. A person can get it in the hospital or at home. Follow the prescription and do not rush the infusion. It is essential to use it as directed. If a person uses it at home, the healthcare provider will teach about it. A person should start feeling better in a few days but do not stop early. Finish the prescription to ensure the infection is fully treated and does not become resistant.

What Is the Dosage Of Vancomycin Hydrochloride?

• Clostridium Difficile-Associated Diarrhea: Take 125 mg by mouth four times a day for ten days.

• Enterocolitis: Take 500 mg to two grams (g) by mouth daily, divided into three to four doses for seven to ten days. The maximum daily dose is two grams.

• In Severe Cases of Clostridium Difficile Infection (CDI): Take 125 mg by mouth four times a day for 10 to 14 days.

• In Complicated CDI: Take 500 mg by mouth four times a day and also use 500 mg rectally every six hours with or without IV (intravenous) Metronidazole (a different medication).

• Both CDI and Enterocolitis: Rectal formulations should be given as a retention enema.

• Recurrence of CDI: The person may be treated again, possibly with a different dosing regimen.

How Effective Is Vancomycin Hydrochloride?

Vancomycin has been around for a long time and was used to treat many bacterial infections. It is very effective but should be used carefully because some bacteria are becoming resistant to it. In most hospitals, a group of doctors and pharmacists make sure it is used the right way. Before giving Vancomycin, doctors check the patient's condition, and the pharmacist looks at their medical records. Nurses tell patients about the drug's side effects, and everyone works together to use it properly. This helps save money and makes sure the medicine keeps working for infections.

What Are the Things to Inform the Doctor Before Taking the Vancomycin Hydrochloride?

Before using Vancomycin hydrochloride, inform the healthcare provider if:

• A person is allergic to Vancomycin hydrochloride or any other medications.

• A person has any medical conditions, like kidney, stomach, hearing, or heart problems.

• Need a low-sodium diet for a person’s health.

• A person has trouble taking pills or getting medicine through a vein.

• If a person is pregnant or planning to be, there are some considerations.

• A person who is breastfeeding should discuss options with their healthcare provider.

• Take other medications, vitamins, supplements, or herbal products, as they can interact with Vancomycin hydrochloride.

• Ask the healthcare provider about possible side effects and what to do if the person experiences any.

How Is Vancomycin Hydrochloride Administered?

Before taking Vancomycin hydrochloride, a pharmacist needs to mix the powder to make a liquid solution.

For Adults:

• If they have C. difficile-associated diarrhea, take 125 mg orally four times a day for ten days.

• If they have staphylococcal enterocolitis, the total daily dose is 500 mg to 2 g, divided into three or four doses, for seven to 10 days.

For Kids Under 18:

• The usual daily dose for C. difficile-associated diarrhea and staphylococcal enterocolitis is 40 mg/kg (milligrams per kilogram), divided into three or four doses for seven to ten days. The total daily dose should not go over two grams.

• To prepare and store the Vancomycin hydrochloride solution, they should get a kit with Vancomycin powder and grape-flavored diluent. A pharmacist will mix them to create the solution. The kit has various strengths and volumes.

What Are the Side Effects of Vancomycin Hydrochloride?

• Infusion-Related Events: Sometimes, during or after a fast Vancomycin infusion, patients may experience reactions like low blood pressure, wheezing, difficulty breathing, hives, itching, or chest and back pain. These typically go away within 20 minutes but may last longer. They are less likely if the infusion is slow.

• Kidney Problems: Vancomycin can sometimes lead to kidney issues, especially if the dose is high or if they are taking other kidney-harming drugs or already have kidney trouble. It can also cause kidney inflammation.

• Stomach and Intestinal Issues: A person might develop symptoms of a condition called pseudomembranous colitis while or after taking antibiotics.

• Ear Problems: In a few cases, Vancomycin has been linked to hearing loss, often in people with kidney problems, prior hearing issues, or when combined with other hearing-affecting drugs. Dizziness and ringing in the ears have also been rarely reported.

• Blood Problems: Some patients, usually after taking a lot of Vancomycin, have experienced low white blood cell counts (neutropenia), which improves when they stop the drug. There have been rare reports of low platelet counts (thrombocytopenia) and extremely low white blood cell counts (agranulocytosis).

• Skin and Injection Site Issues: In some cases, patients have had serious skin reactions like rashes, blistering, and inflammation at the injection site.

• Other Rare Reactions: There have been occasional reports of severe allergic reactions, drug-related fever, nausea, chills, and various skin issues associated with Vancomycin use.

Dietary Considerations:

Usually, antibiotics are not recommended to take with fruit juices or dairy products as they can affect the absorption of the medication. It is recommended to take Vancomycin hydrochloride with water. Follow the doctor’s instructions about food, beverages, or activity restrictions.

Missed Dose:

The medicine should be taken as soon as a person remembers that they have skipped the dose. But it should not be accepted if it is time for the next dose.

Overdose:

In case of a Vancomycin overdose, providing supportive care and maintaining kidney function is recommended. Vancomycin is not effectively removed by dialysis, but using certain methods like hemofiltration and hemoperfusion with a specific resin can help clear it from the body. The lethal doses in animals are much higher than normal human doses.

Storage:

• Store this medication in its original container, tightly sealed, and away from children.

• Keep Vancomycin capsules at room temperature in a dry place, not in the bathroom.

• The oral solution should be stored in the refrigerator.

• When a person no longer needs the medication, do not throw it in the toilet.

• Instead, find a safe way to dispose of it, like a medicine take-back program in the community.

• Keep all medications out of children's reach, especially those with easy-to-open containers, and store them in a secure place.

For Doctors

Indications:

• Vancomycin hydrochloride can be used to treat enterocolitis caused by specific Staphylococcus aureus strains in both adults and pediatric patients under 18 years old.

• It is important to note that administering Vancomycin through injections is not effective for these infections; it must be taken orally.

• However, it is essential to understand that orally administered Vancomycin is not suitable for treating other types of infections.

• To prevent the development of antibiotic-resistant bacteria and preserve the effectiveness of Vancomycin hydrochloride and other antibacterial drugs, Vancomycin hydrochloride should only be used when there is strong evidence or a high suspicion that the infection is caused by susceptible bacteria.

• If lab tests provide information about the specific bacteria and their susceptibility, that data should be considered.

• If such information is unavailable, local infection trends and susceptibility patterns can guide the choice of treatment.

Dose:

Each Vancomycin hydrochloride kit contains powdered Vancomycin hydrochloride for making an oral solution in different quantities. The occurrence of infusion-related events during Vancomycin administration is linked to both its concentration and the speed of delivery. It is generally recommended to use concentrations of up to five mg/mL (milligrams per milliliter) and delivery rates of no more than 10 mg/min (milligrams per minute) in adults, with variations based on the patient's age. In some cases where patients require limited fluid intake, concentrations of up to 10 mg/mL may be considered, but this could heighten the risk of infusion-related events. Generally, a slower infusion rate of 10 mg/min or less is associated with fewer infusion-related issues. However, it is important to note that such events may still occur regardless of the rate or concentration used.

Dosing Considerations:

For Vancomycin hydrochloride, the provided powder needs to be mixed into an oral solution by a healthcare provider, often a pharmacist. Here are the recommended dosages:

For Adults:

• C. Difficile-Associated Diarrhea: The typical dose is 125 mg, taken orally four times a day for ten days.

• Staphylococcal Enterocolitis: The total daily dosage ranges from 500 mg to 2 g taken orally, divided into three or four doses daily for seven to ten days.

Pediatric Patients (Under 18 Years Old):

• For both C. difficile-associated diarrhea and staphylococcal enterocolitis, the usual daily dosage of Vancomycin hydrochloride is 40 mg per kilogram of body weight, divided into three or four doses, and taken for seven to ten days. The total daily dosage should not exceed two grams.

What Are the Pharmacological Aspects of Vancomycin Hydrochloride?

Pharmacodynamics:

Vancomycin is a complex nonribosomal peptide antibiotic, often used as a last-resort treatment when other antibiotics have failed. It has demonstrated effectiveness against a wide range of microorganisms in both laboratory settings and clinical infections. These include various bacteria such as Listeria monocytogenes, Streptococcus pyogenes, Streptococcus pneumoniae (even resistant strains), Streptococcus agalactiae, Actinomyces species, and Lactobacillus species. In vitro, combining Vancomycin with an aminoglycoside can have a synergistic effect against many strains of Staphylococcus aureus, Streptococcus bovis, enterococci, and the viridans group Streptococci. The study suggests adjusting Vancomycin dosage and considering the use of steroids can impact its success in treating this type of meningitis.

Mechanism of Action:

Vancomycin primarily works by stopping the formation of the cell wall in bacteria, leading to their death. It does this by blocking the incorporation of certain building blocks (N-acetylmuramic acid and N-acetylglucosamine) into the peptidoglycan structure, which is a crucial part of the cell wall in gram-positive bacteria. Vancomycin binds to the ends of these building blocks, called D-alanyl-D-alanine moieties, and prevents them from becoming part of the peptidoglycan structure. Additionally, Vancomycin affects the permeability of the bacterial cell membrane and inhibits RNA (ribonucleic acid) synthesis. It is important to note that Vancomycin does not lose its effectiveness due to resistance developed against other antibiotics. However, it does not work against gram-negative bacteria, mycobacteria, or fungi in laboratory settings.

Pharmacokinetics:

Vancomycin is not effectively absorbed by the body when taken orally. When volunteers took Vancomycin capsules multiple times over a week, the concentration of Vancomycin in their feces was high, but there were no significant amounts of the drug detected in their blood or urine. In anephric subjects (people with no kidney function) without inflammatory bowel disease who took two grams of Vancomycin oral solution daily for 16 days, only very low levels of Vancomycin were found in the blood of some subjects, and others had none in their blood. When individuals with normal kidney function and C. difficile-associated diarrhea took two grams of Vancomycin daily, high levels of the drug were present in their feces, but very low levels were in their blood. In cases where patients with active C. difficile-associated diarrhea took Vancomycin orally over multiple doses, there might be detectable amounts of the drug in their blood, and if they have kidney problems, it could accumulate. It is important to note that elderly individuals have reduced clearance of Vancomycin from their system.

Toxicity:

• Vancomycin LD50 in mice is 5000 mg/kg orally, and the lethal intravenous dose is around 319 mg/kg in rats and 400 mg/kg in mice.

• Common side effects include nausea, abdominal pain, and low potassium levels, more prevalent in those over 65.

• Nephrotoxicity, kidney issues, and ototoxicity (hearing problems) can occur. Neutropenia (low white blood cells) and thrombocytopenia (low platelet count) have been reported.

• Rapid Vancomycin infusion can lead to reactions like low blood pressure, wheezing, and hives, which usually resolve within 20 minutes.

• In infants, no hearing loss or kidney issues from maternal intravenous Vancomycin use.

• Excretion of Vancomycin in human milk after oral use is uncertain, so caution is advised for nursing mothers.

• Safety and efficacy in pediatric patients are not definitively established.

• Older patients may need longer treatment, and kidney monitoring is vital, especially if they are over 65.

Clinical Studies:

In trials, Vancomycin hydrochloride was tested in 266 adults with C. difficile-associated diarrhea (CDAD), with a recommended dose of 125 mg taken orally four times daily for ten days. The participants were 18 years or older and had not received other relevant treatments within 48 hours prior to the study. CDAD was defined as having at least three loose bowel movements within 24 hours, along with specific diagnostic markers. Those with severe CDAD, certain medical conditions, or who were pregnant were excluded. Efficacy was measured by clinical success (resolution of diarrhea and no severe abdominal discomfort by Day 10) and time to diarrhea resolution. The median time to resolution was five days in one trial and four days in another. Recurrence of CDAD happened in some cases after treatment. Strains of C. difficile were identified, and clinical success rates varied based on strain. Recurrence rates also differed among strains.

What Are the Contraindications of Vancomycin Hydrochloride?

• Vancomycin hydrochloride should not be used in patients who are known to be allergic to Vancomycin.

• Elderly patients, due to age-related renal changes, increased volume distribution, and drug buildup, are at higher risk of intravenous Vancomycin-related toxicity, necessitating vigilant monitoring and cautious dosing.

• Vancomycin use in pregnancy requires a benefit-risk assessment, careful maternal blood monitoring to reduce fetal risks, and consideration of dosage adjustments due to pharmacokinetic changes.

• Intravenous Vancomycin excreted in breast milk can affect the baby's health; nursing mothers on it should consult their healthcare provider, and oral Vancomycin with minimal systemic absorption is preferred for breastfeeding women treating Clostridioides difficile infections.

• Impaired renal function can cause Vancomycin accumulation, requiring dose adjustments and monitoring; patients should report kidney-related symptoms.

• Prolonged or improper Vancomycin use can cause bacterial resistance, including Vancomycin-resistant Enterococci (VRE); vigilance, stewardship, and patient adherence are crucial to prevent multidrug-resistant infections.

Warnings and Precautions:

Vancomycin Hydrochloride Oral Use:

• Vancomycin hydrochloride must be taken orally for C. difficile-associated diarrhea and staphylococcal enterocolitis.

• Oral Vancomycin is not effective for other types of infections.

• For parenteral (IV) Vancomycin therapy, consult the IV preparation.

Systemic Absorption:

• Patients with kidney issues, colitis, or intestinal disorders may experience significant systemic absorption.

• Serum Vancomycin levels may reach therapeutic levels in these cases, particularly in patients with renal insufficiency, colitis, or those taking aminoglycoside antibiotics.

• Monitoring Vancomycin levels in the blood may be necessary in some situations.

Nephrotoxicity:

• Renal issues, including renal failure and increased blood creatinine levels, can occur during or after oral Vancomycin therapy.

• The risk of nephrotoxicity is higher in patients over 65 years of age.

Ototoxicity:

• Ototoxicity, which may be temporary or permanent, has been reported in patients taking Vancomycin.

• It is more common in patients receiving high intravenous doses, those with pre-existing hearing problems, or those using other drugs that can harm hearing.

• Hearing tests can help minimize this risk.

Severe Dermatologic Reactions:

• Severe skin reactions, such as toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), have been associated with Vancomycin use.

• Vancomycin hydrochloride should be discontinued at the first sign of these conditions.

Potential for Microbial Overgrowth:

• Vancomycin hydrochloride use may lead to the overgrowth of non-susceptible bacteria.

• Appropriate measures should be taken if superinfection occurs.

Development of Drug-Resistant Bacteria:

• Prescribing Vancomycin hydrochloride without a proven or strongly suspected bacterial infection is unlikely to benefit the patient and increases the risk of drug-resistant bacteria.

Hemorrhagic Occlusive Retinal Vasculitis (HORV):

• HORV, including permanent vision loss, has occurred in patients receiving Vancomycin in the eye (intracameral or intravitreal) during or after cataract surgery.

• The safety and effectiveness of Vancomycin for this use have not been well-established through adequate studies, and it is not recommended for preventing endophthalmitis.

What Are the Drug Interactions of Vancomycin Hydrochloride?

• Combining Vancomycin with other medications may heighten the risk of adverse effects and toxicity.

• Dosing adjustments, monitoring, and alternative treatment should be considered when using Vancomycin alongside specific medications.

• Caution is warranted when combining Vancomycin with nephrotoxic agents like aminoglycosides, amphotericin products, and IV contrast agents.

Special Considerations:

Pregnancy:

• Vancomycin use in the second and third trimesters shows no adverse pregnancy-related outcomes.

• Vancomycin did not cause developmental effects when given intravenously to pregnant rats and rabbits at recommended human doses.

Lactation:

• Expected minimal systemic absorption of Vancomycin with oral administration.

• Consider the benefits of breastfeeding along with the maternal clinical need for Vancomycin hydrochloride and its potential effects on the infant.

Pediatric Use:

• Vancomycin hydrochloride is indicated for pediatric patients under 18 years old to treat C. difficile-associated diarrhea and Staphylococcus aureus enterocolitis.

Geriatric Use:

• Geriatric patients are at higher risk of nephrotoxicity during and after Vancomycin treatment.

• They may have slower treatment responses.

• Appropriate treatment duration should be maintained for geriatric patients.