Nitrofurantoin – Drug class, mechanism of action, uses, dosage and side effects

Nitrofurantoin - Drug class, mechanism of action, uses, dosage and side effects

What is nitrofurantoin?

Nitrofurantoin is a drug which belongs to the class of antibiotics. Antibiotics are the drugs which are used to fight bacteria in the body and are used in bacterial infections. The drug is used for the treatment of bacterial infections as it stops the growth of bacteria. Antibiotics do not affect viruses therefore, nitrofurantoin cannot be used in viral infections. Nitrofurantoin is primarily used for the treatment of urinary tract infections caused by several types of bacteria.

Nitrofurantoin is effective against several types of bacteria including E. Coli, Enterobacter cystitis, Enterococcus, Klebsiella, and Staphylococcus aureus. The drug usually interferes with the production of the bacterial cell wall, proteins, and DNA which are essential for the survival of bacteria. Nitrofurantoin is manufactured by different companies and is available in different dosage forms. It is available in the form of tablets, capsules, and oral suspension.

Nitrofurantoin description, IUPAC name, molecular formula, weight, and structure

Nitrofurantoin is a drug which is recognized as an antibacterial due to which it is used for the treatment of bacterial infections. The drug is used for the treatment of bacterial urinary tract infections and is chemically described as 1-[[[5-nitro-2-furanyl]methylene] amino]-2,4-imidazolidinedione. Nitrofurantoin works by preventing the growth of bacteria or by killing the bacteria which cause harmful infections. The drug prevents the bacteria from synthesizing its proteins, DNA, and cell wall without which the bacteria cannot survive. This effect results in the death of the bacterium.

IUPAC name: 1-[(E)-(5-nitrofuran-2-yl)methylideneamino]imidazolidine-2,4-dione

Molecular formula: C8H6N4O5

Molecular weight: 238.159 g/mol

Molecular structure:

What is the drug nitrofurantoin used for?

Nitrofurantoin identification

Nitrofurantoin is available in the form of fine yellow powder or in the form of lemon yellow crystals. The drug is odorless and has a bitter taste. Nitrofurantoin is only slightly soluble in water and alcohol while it is practically insoluble in ether. The drug is soluble in dimethylformamide and dimethyl sulfoxide. The aqueous solubility of nitrofurantoin depends upon the temperature as well as the pH. The drug is sensitive to heat and is decolored by exposure to light or by alkali. When the drug is heated it melts, gets decomposed at a temperature of 270 to 272°C and emits toxic fumes of nitroxides.

What are common brand names for nitrofurantoin?

  • Furabid (Goldshield)
  • Niftran 
  • Siraliden
  • Urantoin (Basel) 
  • Urolong (Thiemann)

What is the mechanism of action of nitrofurantoin?

Nitrofurantoin belongs to the class of antibiotics and is used for the treatment of urinary tract infections caused by several types of bacteria. Nitrofurantoin has a unique mechanism of action as compared to other antibacterial drugs as the drug is reduced by bacterial flavoproteins to reactive intermediates. These intermediates have the ability to inactivate or alter bacterial ribosomal proteins and other macromolecules. Such inactivations result in the inhibition of vital biochemical processes of the bacteria including protein synthesis, aerobic energy metabolism, DNA synthesis, RNA synthesis, and cell wall synthesis. At normal therapeutic doses, nitrofurantoin is bactericidal and kills the bacteria in urine. Since the drug has the ability to act by various mechanisms and inhibits a variety of bacterial processes, the bacteria are unable to acquire resistance to the drug. The drug also causes multiple and simultaneous mutations of the target macromolecules leading to the death of the bacteria.

What are the indications of nitrofurantoin?

Nitrofurantoin is a drug which is used primarily for the treatment of urinary tract infections. The drug is used for the treatment of uncomplicated urinary tract infections as well as for the prophylaxis against acute or recurrent uncomplicated urinary tract infections. The drug is also used for the treatment of and prophylaxis against acute or recurrent pyelitis which could either be spontaneous or occur as a result of surgical procedures.

Nitrofurantoin is indicated specifically or the treatment of urinary tract infections which are caused by the susceptible strains of bacteria including Escherichia coli, enterococci, Staphylococcus aureus, as well as the susceptible strains of Klebsiellaand Enterobacter species.

Nitrofurantoin pharmacokinetics

Nitrofurantoin is administered orally in various dosage forms. The drug is readily absorbed from the gastrointestinal tract and is absorbed primarily from the small intestine. The absorption of the drug can be enhanced by the presence of food or by delaying the gastric emptying which results in an enhanced dissolution rate of the drug. This further results in an increased duration of therapeutic urinary concentration. The drug is readily distributed in the body and crosses the placenta. Nitrofurantoin is distributed into breast milk and even crosses the blood-brain barrier. The drug is bound to plasma proteins and protein binding ranges from 20 to 60%. The drug is found in high concentrations in the urine and the kidneys. Nitrofurantoin is metabolized partially, primarily in the liver. As a result of metabolism, a small fraction of the drug is reduced to aminofurantoin. The drug is eliminated by glomerular filtration and tubular secretion and is excreted in urine. About 30 to 50% of the drug is excreted unchanged in urine. The drug may accumulate in patients with impaired renal function leading to toxicity. The plasma half-life of nitrofurantoin is about 20 minutes in patients with a normal renal function which indicates that antibacterial activity in plasma is minimum. The half-life of the drug is increased in patients with impaired renal function.

What is the recommended dosage of nitrofurantoin?

Nitrofurantoin is carefully prescribed to patients with different conditions. The recommended dosages for each condition are as below;

Is it safe to take nitrofurantoin?

For the treatment of uncomplicated urinary tract infection and acute cystitis

The following recommendations are for oral dosage forms except for oral suspension:

In adults, it is advised to give 50 to 100 mg PO 6 hourly. This should be continued for 7 days on average but at least 3 days after urine gets sterile.

In infants, children, and adolescents, it is advised to give 5 to 7 mg/kg PO given in total 4 divided doses per day. This should be continued for 7 days on average but at least 3 days after urine gets sterile.

The following recommendations are for oral suspension:

In adults, it is advised to give 50 to 100 mg PO 6 hourly. This should be continued for 7 days on average but at least 3 days after urine gets sterile.

In children and adolescents (weighing greater than 42 kg) it is advised to give 50 to 100 mg PO 6 hourly. This should be continued for 7 days on average but at least 3 days after urine gets sterile.

In children and adolescents (weighing less than 42 kg) it is advised to give 5 to 7 mg/kg PO given in total 4 divided doses per day. This should be continued for 7 days on average but at least 3 days after urine gets sterile.

As a prophylaxis in predisposed patients to UTI and chronic suppressive therapy for UTI

The following recommendations are for all oral dosage forms:

In adults, it is advised to give a dose in between 50 to 100 mg PO as a single dose just before bedtime.

In infants, children, and adolescents it is advised to not to give more than 1 mg/ kg/ day PO either as a single dose or 2 divided doses just before bedtime.

Are there any dosing considerations needed during nitrofurantoin treatment?

In patients those who are suffering from hepatic impairment, caution is needed in prescribing nitrofurantoin. This medicine is associated with hepatotoxicity so it can worsen up the condition of the patient and in severe cases can be proved fatal for the patient. However, still, no dosage alterations are recommended in the guidelines present in the approved label by FDA.

Those patients who have a medical history of renal impairment or is currently suffering from any renal abnormality in which the CrCl is less than 60ml/ minute, the use of nitrofurantoin is not recommended. In patients who have a CrCl equal or less than 30 ml/ minute, nitrofurantoin is generally well tolerated and more effective.

Use of nitrofurantoin in pregnancy and breastfeeding?

Nitrofurantoin is included in the pregnancy category B by the US Food and Drug Administration. The drug is contraindicated in pregnancy at term (38 to 42 weeks’ gestation) and also during labor or obstetric delivery. In patients who are deficient in G6PD or whose red blood cells lack sufficient quantities of reduced glutathione, nitrofurantoin can induce hemolytic anemia. For these reasons, the drug should be used with caution in pregnancy and other alternatives should be considered for treatment.

Nitrofurantoin enters into breast-milk and is passed from the mother to the infant during the feeding process, therefore, the drug should be used with caution by breast-feeding women. Since the nursing infants are at an increased of adverse events from nitrofurantoin especially those who are deficient in G6PD as the drug can cause hemolytic anemia, a decision should be made whether to discontinue the drug or to discontinue nursing after considering the importance of the drug to the mother. Other alternatives such as cephalexin, trimethoprim or sulfamethoxazole can also be considered during breast-feeding as they are safer than nitrofurantoin.

What are the side effects associated with nitrofurantoin?

Nitrofurantoin can cause a variety of side effects. It can cause common as well as serious side effects. Some common side effects occurring by the use of the drug include:

  • Nausea
  • Vomiting
  • Loss of appetite
  • Stomach pain
  • Diarrhea
  • Numbness in the hands and feet
  • Pain in the hands and feet
  • Weakness
  • Dizziness
  • Headache
  • Drowsiness

These effects can last for a few days or a couple of weeks. However, the drug can also cause some serious side effects which require prompt medical treatment including:

  • Dyspepsia
  • Emesis
  • Pancreatitis
  • Hepatitis
  • Cholestatic hepatitis
  • Peripheral neuropathy including optic neuritis
  • Confusion
  • Depression
  • Asthenia
  • Nystagmus
  • Vertigo
  • Alopecia
  • Muscle weakness
  • Pale skin
  • Jaundice
  • Dark urine
  • Fever
  • Chills
  • Shortness of breath
  • Anaphylactic reaction including pruritus, erythema
  • Arthralgia
  • Myalgia
  • Glucose-6-phosphate dehydrogenase deficiency anemia
  • Thrombocytopenia
  • Hemolytic anemia
  • Megaloblastic anemia
  • Leukopenia
  • Granulocytopenia

What if I overdose nitrofurantoin?

When the drug overdoses, it leads to gastric irritation, nausea, and vomiting. No serious adverse effects have been reported as a result of an overdose. There is no specific antidote for nitrofurantoin. If a patient accidentally ingests too much nitrofurantoin, hemodialysis can be done. However, the recommended treatment in case of an overdose includes gastric lavage and induction of emesis. Since the drug is excreted in urine, a high fluid intake should be maintained in order to promote the urinary excretion of the drug. Reports of the patient should also be monitored at regular intervals including full blood count, renal function tests, liver function tests.

What are the necessary precautions during nitrofurantoin use?

While prescribing the drug, it is necessary to follow precautions in order to avoid any occurrence of adverse effects.

  • Viral infection:

This drug is sometimes given in treating viral infection. It should be kept in mind that nitrofurantoin is not given in viral infections, for example, common cold. In the nonexistence of any susceptible or evident bacteria or even in the presence of prophylactic indication, instead of granting clinical benefit to the patient, there is a chance of the growth of drug-resistant bacteria. Proper counseling should be provided to the patient to complete the course regimen even the condition gets better earlier.

  • In geriatric patients:

Nitrofurantoin is not considered as a safe drug for use in patients who are above 65 years old. Reports have shown the occurrence of pulmonary reactions which have proved fatal in the majority of cases. This has been more common in patients who were given the treatment with this medicine over prolonged periods. Along with this, spontaneous reports had shown a rise in the occurrence of hepatic impairment. In some cases, renal or cardiac injuries were also observed. Peripheral neuropathy is another unwanted effect that is seen in elderly patients. Due to the presence of other concomitant underlying diseases, this medicine has worsened up the situations. As suggested by the Beers Criteria, nitrofurantoin is potentially not an appropriate drug to be administered to geriatric patients.

  • Gastrointestinal diseases:

Majority of the antibiotics are linked with the occurrence of pseudomembranous colitis which can be differentiated in terms of severity from being mild to a life-threatening situation. In the GI tract, overgrowth of bacteria Clostridia may arise when the normal flora is altered on the administration of antibiotics. Pseudomembranous colitis is primarily caused by the toxin which is produced by Clostridia. Patients who are using antibacterial agents are more prone to the development of colitis. On using nitrofurantoin, diarrhea can occur. In such a situation, it is advised to discontinue the drug. In mild cases on the discontinuation of the medicine, the patient gets better. In severe diarrhea, electrolytes and fluids should be immediately administered along with specific protein supplements. Treatment with an antibacterial agent against Clostridium difficile should be immediately started. Before starting the treatment with nitrofurantoin the healthcare provider must take a thorough medical history.

Nitrofurantoin contraindications?

Use of nitrofurantoin is contraindicated in the following conditions:

  • Pulmonary diseases:

Among the most commonly occurring adverse effects of using nitrofurantoin are pulmonary reactions. These reactions can be acute or chronic depending upon the dose of the drug and the time duration for which it is prescribed. Acute pulmonary reactions are usually reversible and occur within the first few days of the therapy. While those termed as chronic reactions occur when the treatment is continued for a prolonged period and thus are irreversible. In those patients who already are predisposed to any of the pulmonary diseases, the use of nitrofurantoin is contraindicated. It is better to closely monitor all patients when they are being given this medicine for any abnormality in normal pulmonary functions.

  • In neonates, infants, and children:

Nitrofurantoin in any dosage form should be avoided for administration to neonates, infants or children as it was reported to interfere with the haemoglobin levels in the blood. It has caused hemolytic anemia in patients with G6DP deficiency and also in patients whose red blood cells are short of reduced glutathione. Neonates are more prone as their systems are not fully developed so the drug should not be recommended for use. Nitrofurantoin should also be avoided in children who have a genetic history of G6PD deficiency or hemolytic anemia.

Nitrofurantoin and hepatotoxicity

The use of nitrofurantoin has rarely been associated with hepatotoxicity, including hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis. Nitrofurantoin macrocrystals capsules are contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with nitrofurantoin. Most acute reactions are self-limiting and resolve spontaneously, although fatalities have been reported. Therapy with nitrofurantoin should be administered cautiously in patients with liver disease. Periodic monitoring of liver function is recommended during prolonged therapy. The drug should be withdrawn immediately if hepatitis or liver damage occurs and is felt to be drug-related. Since nitrofurantoin is partially metabolized by the liver, a reduced dosage may also be necessary to prevent toxicity.

Can I take nitrofurantoin with oral contraceptives?

The concomitant use of oral contraceptives with nitrofurantoin is reported to cause the failure of the contraceptives and has resulted in a large number of unwanted pregnancies. This is a moderate level of drug interaction which is due to the altered plasma levels of the of combined oral contraceptive components. This had lead to the ovulation in the woman. Those females who wish to avoid pregnancies and were using antibiotics were suggested to use other means of contraception, preferably condoms, rings, and patches.

Can I take nitrofurantoin with antacids?

A major extent of interaction was observed in patients to whom antacids and nitrofurantoin were coadministered. Antacids particularly Na salts have been responsible for slowing down both the extent and rate of gastrointestinal absorption. This delay is probably because of the surface absorption phenomena in which the antibacterial agents gets absorbed onto the surface of antacids when orally administered. It is recommended that in order to avoid this, both the drugs are administered separately with at least a gap of 2 hours in between.

Can I take nitrofurantoin with blood thinners?

Mostly prescribed blood thinning agent is warfarin. When warfarin is co-administered with nitrofurantoin the patient develops the risk of bleeding due to an increase in INR. Blocking the formation of vitamin K is also another suggested mechanism in the alteration of normal flora quantity. On the other hand, coexisting infection is also considered a possible risk for the increase in the INR factor. The patients should be observed for signs and symptoms of bleeding. Moreover, INR factor should be regularly checked up especially when the treatment is started or is about to end with nitrofurantoin.

Can I take nitrofurantoin with folic acid?

Pregnant women are usually recommended to take folic acid, especially during the first trimester. They also have to go through recurrent urinary tract infection. When folic acid in form of L-methylfolate is coadministered with nitrofurantoin, plasma levels of L-methyfolate are altered. Nitrofurantoin behaves as an antagonist to folate blocking its binding to the receptors and hence decreasing its efficacy. Reports have shown that the patients who are taking nitrofurantoin have developed folate deficiency.

Can I take nitrofurantoin with cholera live vaccine?

If you are currently being treated with nitrofurantoin or have been treated within the last 14 days, you should talk to your doctor before receiving cholera vaccine, live. Antibiotics like nitrofurantoin may reduce the activity of the vaccine. To ensure adequate vaccine response, you should not receive cholera vaccine, live until at least 14 days after you complete your nitrofurantoin therapy. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Can I take nitrofurantoin with isoniazid?

Using isoniazid together with nitrofurantoin may increase the risk of nerve damage, which is a potential side effect of both medications. atient risk factors include diabetes and age older than 60 years. In some cases, the neuropathy may progress or become irreversible despite discontinuation of the medications.

Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring to safely use both medications. Let your doctor know if you develop weakness, numbness, pain, burning, or tingling in your hands, feet, or limbs. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Can I take nitrofurantoin with lovastatin?

The risk of peripheral neuropathy may be increased during concurrent use of two or more agents that are associated with this adverse effect. Patient risk factors include diabetes and age older than 60 years. In some cases, the neuropathy may progress or become irreversible despite discontinuation of the medications.

Can I take nitrofurantoin with alcohol?

While nitrofurantoin and alcohol do not have any known interactions, it is still not a good idea to mix the two. In fact, it’s a bad idea to drink alcohol while taking any medication, since it can have an adverse effect on a variety of medical conditions. No matter what your health problem, it is likely that alcohol will either make it worse or have no effect on it.

Moderate alcohol consumption (one glass a day for women and two glasses a day for men) has been shown to have no negative effect on nitrofurantoin. However, if you drink excessive amounts, it could cause serious health problems and may reduce the drug’s effectiveness.

If you drink alcohol, no matter how little, you should let your doctor know. There may be other health considerations beyond simply this one drug that need to be factored in when your doctor diagnoses you and prescribes medication for you. For most people, a drink or two each day isn’t seriously detrimental to their health, but what you drink and how often you drink can certainly have an effect on your wellbeing.

How to store nitrofurantoin?

Nitrofurantoin should be stored at a temperature between 68°F and 77°F (20°C and 25°C). it remains stable when stored at this temperature. The drug should be protected from exposure to strong light as this can lead to the decolorization of the drug. For this purpose, the drug is supplied in amber colored bottles. The drug should not be stored in the bathroom as it can get contaminated and should be located at a safe place to keep it out of the reach of children as it may lead to poisoning if they consume it.

What should additional information be provided to the patient?

Before the administration of nitrofurantoin, the healthcare provider should properly counsel the patient. It is advised that:

  • The medicine may cause drowsiness or dizziness so great care is needed when driving or operating any machinery or any other activity in which complete alertness of the user is required.
  • The medicine should be taken at the exact timing which is prescribed to the patient. it is important to keep a time gap of 2 – 4 hours in between two consecutive doses.
  • On using this medicine, the color of urine is changed to rust yellow to brownish. This color change is not important and the patient should ignore it.

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About Miljan Krcobic 363 Articles
Miljan Krčobić. has bachelor degree in Pharmacy.