Trimethoprim: Dosage, Side Effects, Warnings, Precautions, Interactions and Contraindications

It is a synthetic antibiotic available in tablet form for oral administration. Each white tablet contains 100 mg of Trimethoprim.

Trimethoprim is 5 – [(3,4,5-trimethoxyphenyl) methyl] -2,4-pyrimidinediamine. It is a yellowish, odorless, white to light yellow compound with a molecular weight of 290.32 and the molecular formula C14H18N4O3. Used to treat bacterial infections. It works by stopping the growth of bacteria.

Trimethoprim blocks the production of tetrahydrofolic acid from dihydrofolic acid by binding and reversibly inhibiting the required enzyme, dihydrofolate reductase. This binding is much stronger for the bacterial enzyme than for the corresponding mammalian enzyme.

Therefore, Trimethoprim selectively interferes with the bacterial biosynthesis of nucleic acids and proteins.

Trimethoprim is rapidly absorbed after oral administration. It exists in the blood as unbound forms, bound to proteins and metabolized. Ten to twenty percent of trimethoprim is metabolized, mainly in the liver, the rest is excreted unchanged in the urine.

The main metabolites of Trimethoprim are the 1- and 3-oxides and the 3′- and 4′-hydroxy derivatives. The free form is considered to be the therapeutically active form. Approximately 44% of Trimethoprim is bound to plasma proteins.

A single 200 mg dose will result in approximately twice as high serum levels. The half-life of Trimethoprim ranges between 8 and 10 hours.

However, patients with severely impaired renal function exhibit an increase in the half-life of trimethoprim, which requires an adjustment of the dosing regimen or not using the medication in such patients.

The excretion of Trimethoprim is mainly by the kidneys through glomerular filtration and tubular secretion. Concentrations of trimethoprim in the urine are considerably higher than the concentrations in the blood.

After a single oral dose of 100mg, trimethoprim concentrations in the urine varied from 30 to 160mcg / ml during the period of 0 to 4 hours and decreased to approximately 18 to 91mcg / ml during the period of 8 to 24 hours.

A single oral dose of 200 mg will result in approximately two times higher levels of Trimethoprim in the urine. After oral administration, 50 to 60% of Trimethoprim is excreted in the urine in 24 hours, approximately 80% of this is trimethoprim unmetabolized.

Since the normal vaginal and fecal flora is the source of most of the pathogens that cause urinary tract infections , it is relevant to consider the distribution of Trimethoprim in these sites.

The concentrations of Trimethoprim in the vaginal secretions are consistently higher than those found simultaneously in the serum, typically being 1.6 times the concentrations of serum samples obtained simultaneously.

Sufficient Trimethoprim is excreted in the faeces to markedly reduce or eliminate Trimethoprim-sensitive organisms from the fecal flora. Trimethoprim also passes the placental barrier and is excreted in human milk.

Trimethoprim only treats bacterial infections. It will not work for viral infections (eg, common cold, flu). The unnecessary use or excessive use of any antibiotic can lead to a decrease in its effectiveness.

Trimethoprim can also be used to treat some lung infections ( pneumonia carinii pneumonia) and to prevent kidney infections in certain patients.

Trimethoprim is available under the following brands:

  • Primsol.
  • Proloprim.

Doses of Trimethoprim:

  • Oral solution of 50mg / 5ml.
  • 100mg tablets

It must be administered as follows:

For susceptible infections with 100mg orally every 12 hours.

It is unlikely that the prescription of Trimethoprim tablets, in the absence of a proven or very suspicious bacterial infection or a prophylactic indication, will benefit the patient and increase the risk of developing drug-resistant bacteria.

Renal insufficiency:

  • CrCl 15-30 ml/min: 50 mg cada 12 horas.
  • CrCl less than 15 ml / min: 100 mg every 24 hours or avoid use.

Other information:

Safety and efficacy in pediatric patients younger than 2 months have not been established. The effectiveness of Trimethoprim as a single agent has not been established in pediatric patients under 12 years of age.

Pediatric: children under 12 years: safety and efficacy not established.

Trimethoprim tablets should be used only to treat or prevent infections that are suspected to be caused by susceptible bacteria. When culture and susceptibility information is available, they should be considered when selecting or modifying antibacterial therapy.

In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empirical selection of therapy.

For the treatment of initial episodes of uncomplicated urinary tract infections due to susceptible strains of the following organisms: Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Enterobacter species and Coagulase negative Staphylococcus species, including S. saprophyticus.

Culture and susceptibility tests should be performed to determine the susceptibility of the bacterium to Trimethoprim. Therapy can be started before obtaining the results of these tests.

The use of Trimethoprim at high doses and / or for prolonged periods of time can cause depression of the bone marrow that manifests as thrombocytopenia , leukopeniaand / or megaloblastic anemia .

If signs of bone marrow depression appear , treatment with Trimethoprim should be discontinued and leucovorin should be administered to the patient. Some researchers have recommended 5 to 15mg of leucovorin daily.

What are the side effects associated with the use of trimethoprim?

Common side effects of Trimethoprim include:

  • Aseptic meningitis
  • Changes in taste.
  • Cholestatic jaundice .
  • Diarrhea.
  • Erythema multiforme.
  • Dermatitis exfoliativa.
  • Fever.
  • Headache.
  • High level of potassium in blood (hyperkalemia).
  • Hypersensitive reactions.
  • Itching (common)
  • Loss of appetite
  • Low platelet count in the blood ( thrombocytopenia ).
  • Low blood sodium level (hyponatremia).
  • Low white blood cell count (leukopenia, neutropenia).
  • Maculopapular rash (3-7% at 200 mg / day, the incidence is higher with larger daily doses).
  • Megaloblastic anemia.
  • Metahemoglobinemia.
  • Nausea.
  • Phototoxic skin rashes.
  • Severe allergic reaction ( anaphylaxis ).
  • Sensitivity of the skin to sunlight.
  • Stevens-Johnson syndrome.
  • Stomach pain or upset
  • Swollen tongue.
  • Toxic epidermal necrolysis.
  • He retched.

It does not contain all possible side effects and others may occur. Check with your doctor for additional information about side effects.

Warnings and Caution is

Although it can be rare, some people can have very serious and sometimes fatal side effects when taking a medication.

Some side effects of Trimethoprim may occur that usually do not require medical attention. These side effects may go away during treatment as your body adjusts to the medication.

In addition, your health professional can tell you about ways to prevent or reduce some of these side effects. Tell your doctor or seek medical attention immediately if you have any of the following signs or symptoms that may be related to a very serious side effect:

Signs of an allergic reaction, such as rash, hives , itching, red, swollen, blistered or scaling skin with or without fever, wheezing, tightness in the chest or throat, difficulty breathing, swallowing or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue or throat.

The signs of methemoglobinemia are a blue or gray color of the lips, nails or skin, a heartbeat that does not feel normal, seizures, dizziness or fainting, headache, drowsiness, tiredness or weakness or difficulty breathing.

Signs of electrolyte problems such as mood swings, confusion, muscle pain or weakness, heartbeat that does not feel normal, seizures, lack of appetite or upset stomach or vomiting.

Also fever or chills and sore throat (without the flu), pale skin, any bruising or unexplained bleeding, purple spots on the skin or mouth.

It is common to have diarrhea when you take this medicine Trimethoprim. Rarely, a very severe form of diarrhea called diarrhea associated with Clostridium difficile may occur. Sometimes, this has led to a fatal intestinal problem ( colitis ).

It may occur while taking this medication or within a few months after you stop taking it. Call your doctor immediately if you have stomach pain or cramping, very loose or watery stools, or bloody stools. Do not try to treat these stools with another medicine without first talking to your doctor.

Serious hypersensitivity reactions have rarely been reported in patients receiving Trimethoprim. It has been reported that trimethoprim rarely interferes with hematopoiesis, especially when administered in large doses and / or for prolonged periods.

The presence of clinical signs such as sore throat, fever, paleness or purpura may be early indications of serious blood disorders.

Complete blood counts should be obtained if any of these signs are observed in a patient receiving trimethoprim and the medication is discontinued if a significant reduction in the counting of any formed blood element is found.

Clostridium difficile-associated diarrhea (CDAD) has been reported with the use of almost all antibacterial agents, including Trimethoprim tablets, and may vary in severity from mild diarrhea to fatal colitis.

Treatment with antibacterial agents alters the normal flora of the colon and leads to excessive growth of Clostridium difficile.

Clostridium difficile produces toxins A and B that contribute to the development of diarrhea associated with the bacteria. The Clostridium difficile hypertoxin-producing strains cause greater morbidity and mortality, since these infections may be refractory to antimicrobial therapy and may require colectomy .

Clostridium difficile-associated diarrhea should be considered in all patients who have diarrhea after the use of antibiotics. A careful medical history is needed since it has been reported that Clostridium difficile-associated diarrhea occurs more than two months after the administration of antibacterial agents.

If the diarrhea associated with Clostridium difficile is suspected or confirmed, the use of antiobiotics may have to be stopped.

Appropriate management of fluids and electrolytes, protein supplementation, antibiotic treatment of Clostridium difficile and surgical evaluation should be instituted as clinically indicated.

Interactions

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible interactions with other medications and may be monitoring you for it.

Do not start, stop or change the dosage of any medication before first checking with your doctor, health care provider or pharmacist.

  • Trimethoprim has no known severe interactions with other drugs.
  • Trimethoprim has serious interactions with at least 21 different medications.
  • Trimethoprim has moderate interactions with at least 124 different medications.
  • Trimethoprim has mild interactions with at least 29 different medications.

This information does not contain all possible interactions or adverse effects. Therefore, before using this product, inform your doctor or pharmacist about all the products you use.

Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional for additional medical advice, or if you have questions about your health, concerns, or for more information about this medication.

This medicine contains Trimethoprim. Do not take Primsol, Proloprim or TMP if you are allergic to Trimethoprim or any of the ingredients in this medicine.

Keep out of the reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

Long-term effects:
  • Large doses or long-term therapy may interfere with hematopoiesis, monitor signs / symptoms of hematological disorders.
  • Prolonged use can cause superinfection by fungi or bacteria, including Clostridium difficile-associated diarrhea and pseudomembranous colitis, which may occur more than 2 months after antibiotic treatment.

Decreases urinary potassium excretion, can cause hyperkalemia , particularly with high doses, renal failure or when combined with other medications that cause hyperkalemia.

Large doses or long-term therapy may interfere with hematopoiesis, monitor signs / symptoms of hematological disorders.

Prolonged use may cause superinfection by fungi or bacteria, including Clostridium difficile-associated diarrhea and pseudomembranous colitis; It may occur more than 2 months after antibiotic treatment.

Hypersensitivity reactions reported, be cautious in patients with renal or hepatic impairment.

Be cautious in patients with potential for folic acid deficiency, including chronic malnourished anticonvulsant therapy or the elderly; Folic acid (vitamin B9) can be administered concomitantly without interfering with the antibacterial action of Trimethoprim.

Some dosage forms may contain benzyl alcohol and derivatives; avoid in newborns. Not indicated for prophylactic or prolonged administration in otitis media at any age.

Pregnancy and breastfeeding

Trimethoprim enters breast milk. Consult your doctor before breast-feeding.

Use Trimethoprim with caution during pregnancy if the benefits outweigh the risks, studies in animals show risk and there are no studies in humans or studies were not conducted in animals or humans.

What should I tell my doctor before taking trimethoprim?

If you are allergic to trimethoprim or any other component of this medication, to any drug like this, any other drugs, food, or other substances.

Tell your doctor about the allergy and signs you had, such as rash, hives, itching, difficulty breathing, wheezing, coughing, swelling of your face, lips, tongue or throat, or any other signs.

Tell your doctor and pharmacist about all your medications (prescription or over-the-counter, natural products, vitamins) and health problems.

You should verify that it is safe for you to take this medication with all your additional medications and health problems. Do not start, stop or change the dose of any medication without checking with your doctor.

Some Things You Should Know or Do While Taking Trimethoprim

Tell all of your health care providers that you take this medication. This includes your doctors, nurses, pharmacists, dentists, and laboratory workers since this medication may affect certain laboratory tests.

To get the most benefit, do not miss the doses, do not use it for longer than they have been told and continue taking the medication according to what your doctor tells you, even if you feel well, or a second infection can happen.

This medication may cause sunburn more easily, be careful if you are in the sun, and tell your doctor if the sun is burning easily while you are taking this medication.

If you are taking Phenytoin (antiepileptic), talk to your doctor. You may need to monitor your blood test more closely while you are taking it.

If you are 65 or older, use this medication carefully, you may have more side effects.

Tell your doctor if you are breast-feeding or are pregnant or plan to become pregnant. You will have to discuss the benefits and risks of using this medicine while you are pregnant or for your baby.

What do I do if I have problems with a dose?

Take the missed dose as soon as you think about it, if it is close to the time of your next dose, skip the missed dose and go back to your normal time. Do not take 2 doses at the same time or additional doses.

If you think there has been an overdose, call your poison control center or get medical attention right away. Prepare to tell or show what was taken, how much, and when it happened.

Signs of acute overdosage with trimethoprim may appear after ingestion of 1 gram or more of the medication and include nausea, vomiting, dizziness, headaches, mental depression, confusion and depression of the bone marrow.

The treatment consists of gastric lavage and general support measures. The acidification of the urine will increase the renal elimination of Trimethoprim. Peritoneal dialysis is not effective and hemodialysis is only moderately effective to eliminate the medication.

How do I store and / or discard Trimethoprim Tablets?

Store at room temperature in a dry place, protect from light

Keep all pills / tablets in a safe place, out of the reach of children and pets.

Throw away unused or expired pills / tablets. Do not flush the toilet or pour it down a drain unless instructed to do so. Ask your pharmacist if you have questions about the best way to rule out pills / tablets. There may be drug return programs in your area.

Use and Disclaimer of Consumer Information Liability

If your symptoms or health problems do not improve or if they get worse, call your doctor.

Do not share your medications with others and do not take someone else’s medication.

Have a list of all your medications (prescription drugs, natural products, vitamins) on hand. Give this list to your doctor.

Talk to your doctor before starting any new medicine, including prescription or over-the-counter medications, natural products, or vitamins.

Some medications may have another patient information booklet. Check with your pharmacist. If you have any questions about Trimethoprim, talk to your doctor, nurse, pharmacist or other health care provider.

If you think there has been an overdose, call your poison control center or get medical attention right away. Prepare to tell or show what was taken, how much, and when it happened.

Information for patients

Patients should be advised that antibacterial medications, including Trimethoprim tablets, should be used only to treat bacterial infections. They do not treat viral infections (for example, the common cold).

When Trimethoprim tablets are prescribed, to treat a bacterial infection, patients should be told that although it is common to feel better at the beginning of therapy, the medication should be taken exactly as indicated.

Skipping doses or not completing all treatment may decrease the effectiveness of immediate treatment and increase the likelihood that the bacteria will develop resistance and are not treatable with Trimethoprim tablets, or other antibacterial drugs in the future.

Diarrhea is a common problem caused by antibiotics that usually ends when the antibiotic is stopped.

Sometimes, after starting antibiotic treatment, patients may develop watery, bloody stools (with or without stomach cramps and fever) even two or more months after taking the last dose of the antibiotic.

If this happens, patients should contact their doctor as soon as possible.