Methenamine - Indications, Dosage, and Adverse Drug Reactions

Overview

Methenamine is an antibacterial medication used to treat or prevent urinary tract infections in adults and children over six years old. It works by inhibiting the urinary tract's production of formaldehyde, which does not kill bacteria but prevents bacteria from multiplying in urine; thereby, formaldehyde acts as a bacteriostatic agent and prevents bacterial growth and the development of urinary tract infections. Methenamine has been approved by the US Food and Drug Administration (FDA) for recurrent urinary tract infection (UTI) prevention in patients aged six and above.

Drug Group

Methenamine belongs to the urinary anti-infective drug class. Urinary anti-infectives can be prescribed to deal with or prevent urinary tract infections. Methenamine, Nalidixic acid, and Nitrofurantoin are commonly used medicines. These medications have large concentrations in urine and are useful for treating urinary tract infections or as a preventative measure.

Indications

• Methenamine is recommended for the preventive or suppressive treatment of recurrent urinary tract infections when prolonged therapy is required.

• This medication should only be administered after other antimicrobial drugs have been used to eradicate the infection.

• Methenamine should only be used to treat or prevent illnesses caused by susceptible bacteria in order to minimize the emergence of drug-resistant bacteria and retain the effectiveness of Methenamine and other antibacterial medications. When culture and susceptibility data are available, these data should be used to select or alter antibiotic therapy. In the lack of such data, local epidemiology and susceptibility patterns may help with provisional medication selection.

Contraindications

Methenamine is not recommended for patients who have renal failure, severe hepatic failure, or severe dehydration. Methenamine preparations should not be given to patients who are taking sulfonamides, as some sulfonamides can create an insoluble precipitate in urine that reacts with formaldehyde.

Dosage Forms and Available Strengths

• The medication Methenamine hippurate is used to treat urinary tract infections in adults and children aged 12 and older. It is taken two times a day, in the morning and evening. For kids up to six years old, the dosage and use ought to be decided with the aid of a doctor. For kids six to twelve years old, the dosage is 500 mg to at least one gram two times a day, in the morning and evening.

• Methenamine mandelate is also used to treat urinary tract infections in tablets, enteric-coated tablets, solutions, and suspensions. Oral dosages of one gram for adults and kids 12 years and older, 18.3 mg per kilogram for children up to six years old, and 500 mg (milligrams) for children 6 to 12 years old should be given four times a day. The dosage is based on body weight for children up to 6 years of age and should be taken after meals and at bedtime.

Warnings

Methenamine at high doses (eight grams daily for three to four weeks) has been reported to cause bladder irritation, painful and frequent urination, albuminuria (urine that exhibits an abnormally high level of the protein albumin), and severe hematuria (the presence of red blood cells or blood in the urine characterizes the medical condition.).

Precautions

Methenamine, an antibiotic, is not advised for people who do not have a proven or suspected bacterial infection or a prophylactic reason.

• Keeping urine at an acidic pH is critical, especially when treating infections caused by urea-splitting organisms like proteus and pseudomonas.

• Serum transaminase levels slightly rose during therapy in several studies but regained normality while patients were still taking Methenamine.

• It is suggested that liver function tests be performed on individuals using the medicine regularly, especially those with liver impairment.

• The safety of Methenamine in early pregnancy has not been confirmed, while safety in the third trimester is recommended but not proven. Due to the presence of Methenamine and Formaldehyde in urine, Methenamine taken during pregnancy may interfere with urine estriol assays. Enzymatic hydrolysis can get around this problem.

• The product contains FD&C Yellow No. 5 (Tartrazine), which may cause allergic responses in sensitive people.

For Patients

What Is Urinary Tract Infection?

UTIs are infections that can arise in any area of the urinary system, including the kidneys, ureters, bladder, and urethra. Bacteria from the skin or rectum frequently enter the urethra and infect the urinary tract. The most frequent UTIs are bladder infection, cystitis, kidney infection, or pyelonephritis (an acute, severe kidney inflammation brought on by a bacterial infection). A burning sensation while urinating, frequent urination, an often urge for urination but incomplete urination, discomfort or pressure in the back or lower abdomen, pain in the pelvic region, blood in urine, cloudy, dark, or strange urine blended with blood in certain instances, fatigue, fever and chills, nausea, and or vomiting are all symptoms of UTIs.

How Does Methenamine Work?

Methenamine, a drug, lacks antibacterial properties in alkaline environments. Still, in acidic environments, hydrolyzed to formaldehyde, which is highly bactericidal and works by denaturing bacteria's proteins and nucleic acid. However, certain bacteria, like Proteus sp., can alkalize urine, inhibiting its beneficial activity. The drug's salt component, like hippuric acid, maintains urine's acidic state.

What Are the Clinical Uses of Methenamine?

Methenamine is an antibiotic used to treat urinary tract infections and prevent recurrence. It eliminates bacteria causing these infections and is typically used long-term. However, it is ineffective for colds, flu, or viral infections.

How Is Methenamine Administered?

Methenamine is a medication that comes in tablet and liquid form, typically taken twice a day or four times a day. It should be taken as directed on the prescription label and with the help of a doctor or pharmacist. The tablets should be swallowed whole, not crushed or broken, and mixed with water or food. To ensure even distribution, shake the liquid well before each use.

This medication can be administered in two ways: through Methenamine hippurate tablets, which are taken orally twice a day, and Methenamine mandelate tablets, which are taken orally four times daily. For adults and children, 12 years of age and over, one gram of Methenamine hippurate tablet or Methenamine mandelate is given. In comparison, for children 6 to 12 years old, 500 milligrams to one gram of Methenamine hippurate or Methenamine mandelate tablets can be taken. For kids up to six years old, the use and dose need to be decided by a doctor.

What Are the Side Effects of Methenamine?

Methenamine could result in negative side effects. Inform the doctor if any of the following symptoms are severe or persistent:

• Stomach upset.

• Vomiting.

• Diarrhea.

• Cramps in the stomach.

• Appetite loss.

Call the doctor right away if the patient has itching, hives, or skin rash (allergic response).

What Are the Things to Inform the Doctor Before Taking Methenamine?

• If sufferers are allergic to Methenamine, Aspirin, Tartrazine (a yellow dye in some processed foods and pharmaceuticals), or any other drugs, notify the doctor and pharmacist.

• Inform the medical doctor and pharmacist about all prescription and over-the-counter (OTC) medicines sufferers take, consisting of antacids, Sulfamethizole, diuretics (water pills), and vitamins.

• Inform the doctor if patients have renal or liver disease or if patients have ever had it.

• Inform the health practitioner if patients are pregnant, intend to be pregnant, or are nursing. Consult the health practitioner if sufferers turn out to be pregnant even after taking Methenamine.

Dietary Considerations

Methenamine, a drug that can cause stomach upset, should be taken with food or milk.

Missed Dose

Take a missed dose as soon as patients remember it, but skip it if it is almost time for the subsequent dose, and retain the everyday dosing schedule, no longer taking a double dose.

Overdose

If an overdose occurs, contact the poison control helpline. If the sufferer collapses, has a seizure, struggles with breathing, or can not be awakened, immediately call emergency services.

Storage and Disposal

To properly store medication, keep it tightly closed, out of sight and reach of children, and at room temperature. Dispose of unneeded medicinal drugs in unique approaches to save pets, children, and others from ingesting the drugs. To dispose of medication through a medicine take-back program, contact the pharmacist or visit the FDA's Safe Disposal of Medicines website.

To prevent poisoning in children, it is crucial to keep medication out of their sight and reach. Many containers, which consist of weekly tablet minders, eye drops, creams, patches, and inhalers, are not child-resistant and can be opened without any trouble. To protect these medicines, lock the safety caps and place the medication in a safe location.

For Doctors

Pharmacodynamics

When ingested orally, Methenamine hippurate exhibits antibacterial activity in the urine within half an hour, while its administration twice daily results in continuous antibacterial activity.

Chemical Taxonomy

Methenamine, a cage-like organic compound similar to adamantane, is used in salt to treat urinary tract infections.

Mechanism of Action

Methenamine does not exhibit antibacterial effects in an alkaline environment (pH more than or equal to 6), yet it is hydrolyzed to formaldehyde in a more acidic environment (pH less than 6). Formaldehyde is thought to be highly antibacterial. Formaldehyde has a nonspecific antibacterial action that denatures bacteria's proteins and nucleic acids. Certain bacteria, such as Proteus sp., can alkalinize urine, reducing formaldehyde's beneficial effect. The primary function of the drug's salt component, such as hippuric acid, is to keep the urine acidic.

Pharmacokinetics

• Absorption: Methenamine is rapidly absorbed after oral administration.

• Metabolism: Gastric acidity hydrolyzes 10 to 15 percent of an oral dose of Methenamine to formaldehyde and ammonia, in which formaldehyde acts as an antiseptic when in acidic urine (pH<6).

• Excretion: Methenamine is primarily eliminated by the kidneys, with a three- to four-hour elimination half-life and 70 to 90 percent of a single oral dose remaining unchanged in urine within 24 hours.

Toxicity

Methenamine treatment results in minor adverse events in less than 3.5 percent of patients, including upset stomach, dysuria, nausea, and rash.

Drug Interactions

1. Methenamine may interact with other medications, such as

• Sulfonamide drugs, such as sulfa antibiotics.

• Urinary alkalinizers include antacids, Sodium bicarbonate, potassium, and sodium citrate. Methenamine should not be used during or around food consumption because it may create interactions.

2. Additionally, combining certain medications with alcohol or nicotine may result in problems.

3. Other medical issues, such as dehydration, kidney disease, or liver illness, should be brought to the doctor's attention. Methenamine may potentially exacerbate negative effects in those who have severe renal or liver problems.

Clinical Studies

Several clinical trials have assessed Methenamine's efficacy in minimizing the incidence of urinary tract infections (UTIs).

• A multicenter, open-label, randomized, non-inferiority trial comparing the efficacy of Methenamine hippurate for avoiding the incidence of recurrent Urinary Tract Infections (UTIs) with the existing endorsed prophylaxis of day-by-day low-dose antibiotics was conducted. During the 12-month treatment period, the incidence of antibiotic-treated urinary tract infections (UTIs) was 0.89 per person per year in the antibiotics group and 1.38 episodes in the Methenamine hippurate group, with an absolute difference of 0.49 episodes.

• A Cochrane review found that Methenamine hippurate may help prevent urinary tract infections (UTIs), although it recommended more randomized controlled trials.

Use in Specific Populations

• Pregnancy: Methenamine, a pregnancy medication, is classified as a Category C risk because it has no proven uses during labor or delivery. Safety during the third trimester is recommended but not proven. The effects of the medicine during labor and delivery are unknown, and there are no known uses for it during these times.

• Lactation: Breastfeeding is not recommended while taking Methenamine.

• Pediatric Use: Methenamine’s use and dose in children must be assessed by a doctor.

• Geriatric Use: The study of Methenamine in older individuals is limited, making it unclear whether Methenamine functions similarly to younger adults or if it causes different side effects or problems.

• Renal Impairment: Methenamine should not be used in individuals with renal impairment because of the higher possibility of side effects and the scarcity of data on its effects in these patients. In individuals with significant renal impairment or dehydration, Methenamine salts (Methenamine hippurate or Methenamine mandelate) but not the base are contraindicated. The kidney excretes Methenamine, which is concentrated in the urine. Salts can precipitate and induce crystalluria in people with limited urine output.

• Hepatic Impairment: It should also not be administered in patients with severe hepatic impairment due to the increased risk of reversible elevations in liver function tests.