Nitrofurantoin - Indications, Contraindications, Dosage, and Warnings

Overview

Nitrofurantoin comes under the category of antibiotics that are specifically authorized for treating urinary tract infections in humans. Though it is considered to be an antibiotic, it does not seem to be fruitful for other infective conditions apart from urinary tract infections (UTIs). The Food and Drug Administration (FDA) - the drug regulatory body of the United States - endorsed the usage of Nitrofurantoin for UTIs in the year 1953. It is reported to be effective for infants (over three months) and adult patients. It is marketed in both pill and suspension forms.

How Does Nitrofurantoin Work?

Nitrofurantoin works by specifically destroying certain bacteria that potentially precipitate infections in the urinary tract. The chemical structure of Nitrofurantoin is quite large - macrocrystal. The macrocrystal nature of Nitrofurantoin makes it difficult to get absorbed from the intestine into the circulating bloodstream. It compromises the availability of Nitrofurantoin in the blood; instead, it piles up in the urine, precipitating a remarkable drug concentration in the urine. This property of Nitrofurantoin makes it ideal for urinary tract infections as the drug is readily concentrated in the urine, thereby directly acting on the infections concerning the urinary tract. When Nitrofurantoin encounters a bacterial pathogen, it transforms into its reactive form. The reactive constituent in the Nitrofurantoin completely disrupts the biochemical activities in the bacterial cell. The genetic material synthesis, energy production, and other crucial processes going on within the bacterial cell get interrupted, and the bacteria eventually perish. Hence, it is considered to be bactericidal (kills bacteria) in nature.

Uses

Nitrofurantoin is prescribed for tackling urinary tract infections, typically involving the lower tract, that are uncomplicated. At times, it is also advised to check the recurrence of UTIs in patients who encounter UTIs more frequently.

Available Doses and Dosage Forms

Nitrofurantoin is available in the market in both pill form and suspension (fluid) forms. A pill can be either a tablet or a capsule. Suspension forms are routinely advised for younger population groups, including infants and children, who cannot take up the pill form.

• Dosage Forms: Suspension, tablets, capsules, and sustained-release tablets.

• Dosage for Adults Under the Age Category 18 to 64 Years: 50 to 100 milligrams (mg) advised four times daily (six hourly).

• Dosage for Children Under the Age Category 12 to 18 Years: 100 mg twice every day.

• Dosage for Children Under One Month to 12 Year Age Group: Five to seven mg per kilogram (kg) of body weight in a day, consumed in four doses.

• Dosage for Prevention of Recurring UTIs in Adults and Children Under 12 Years: 50 to 100 mg once a day.

Warnings

• Respiratory Issues: Diverse pulmonary reactions are reported in patients who took Nitrofurantoin for a significant period. In the event of pulmonary reactions, the patients are instructed to withdraw the drug. Pulmonary reactions in the form of grave lung issues like pulmonary fibrosis (lung tissue hardens, giving rise to scar) and diffuse interstitial pneumonitis ( interposed material in between the lung alveolar cells swollen up) are encountered and demand medical attention at the earliest. Long-term administration of Nitrofurantoin hence necessitates pulmonary monitoring. Patients should immediately report it to the concerned doctor and seek treatment.

• Hemolytic Anemia: Patients who are under treatment using Nitrofurantoin carry the likelihood of developing hemolytic anemia. Nitrofurantoin triggers hemolytic anemia in individuals who exhibit insufficiency of the enzyme glucose-6 phosphatase. Patients are advised to instantly stop the medicine intake in the event of anemia.

• Liver Disorders: Occasionally, patients are reported to develop liver disorders like jaundice (yellowing of the skin) and hepatitis (improper liver function). Liver issues are mostly encountered upon prolonged intake of Nitrofurantoin; hence, a close evaluation of the liver enzymes should be made to ensure proper liver functioning.

• Nerve Disorders: Consistent intake of Nitrofurantoin precipitates neurological issues like peripheral neuropathy, where the person experiences paralysis and anesthesia (numbness) in feet and palms.

• Compromised Kidney Functions: Individuals with compromised kidney function hold the risk for Nitrofurantoin build-up in the kidney, leading to toxicity.

• Diarrhea: Nitrofurantoin is also reported to elicit Clostridium difficile-associated diarrhea (CDAD). Antibiotics significantly impact the normal bacterial colonies present in the intestines and favor the growth of Clostridium difficile, which eventually gives rise to persistent diarrhea.

For Patients:

What Are Urinary Tract Infections?

Urinary tract infections (UTIs), as the name suggests, are bacterial infections that typically involve the urinary tract extending from the kidneys to the urethra through which the urine is passed out. The bacteria can infect anywhere in the urinary tract, encompassing the urethra, bladder, ureter, and kidney. UTIs are routinely precipitated by bacteria like Escherichia coli, Staphylococcus saprophyticus, Pseudomonas aeruginosa, Enterococcus faecalis, Klebsiella pneumoniae, and Staphylococcus aureus. These bacteria somehow gain access to the urinary tract and precipitate urinary infections. The affected person elicits severe pain while passing urine. In addition, the person experiences abdominal pain, typically in the lower abdominal area. The person feels to pass urine more frequently, and often, the urine appears blood-tinted. There will be an associated rise in the body temperature. The person feels worn out and extremely drenched. Antibiotics are advised to tackle urinary tract infections.

When and Why Is Nitrofurantoin Prescribed?

Nitrofurantoin is advised to check bacterial growth in the urinary tract. As the medicine contains large crystals of Nitrofurantoin, it does not gain pronounced access into the bloodstream by absorption. Consequently, Nitrofurantoin piles up in the urine, making it more available in the urinary system than in the circulatory system. In infections involving the urinary tract, the bacteria tend to grow and reside within the urinary tract. Nitrofurantoin, therefore, works well on bacterial growth in the urinary tract. However, it cannot tackle other systemic infections and complicated urinary infections.

Things to Inform the Doctor Before Taking Nitrofurantoin:

Proper communication between the doctor and patient is essential to make sure that the specified medicine is suitable for the health condition of the patient. Failure to which often projects complications and other severe side effects on the patients. Some of the valuable information that should be shared with the doctor before initiating the administration of Nitrofurantoin includes the following:

• Patients are instructed to report prior allergic responses toward any of the constituents in the Nitrofurantoin pill. Further intake of the Nitrofurantoin pill can trigger a potential allergic response in the individual’s body. Details of drug allergy, if any, should be provided to the doctor to prevent complications.

• Detailed history encompassing all the information regarding other underlying disease conditions should be shared with the doctor. Patients suffering from certain diseases like anemia (low red cell count), lung issues, and liver disease are more likely to develop other health complications upon intake of Nitrofurantoin. Hence, such patients should be treated cautiously.

• If the patient is already under treatment for some other health conditions, there is a possibility for those pills to react with Nitrofurantoin and bring about unwanted effects, significantly affecting the effects of both drugs. To keep a check on those effects, patients should provide all the available and accurate information regarding the undertaking medications, including dietary supplements.

• Pregnant women should strictly report their pregnancy status to the concerned doctor. Nitrofurantoin can influence pregnancy nearing the full term (38 to 42 weeks). No relevant data are available regarding the effect of Nitrofurantoin in the early stages of pregnancy. However, animal studies suggested no significant toxicity to the child in the womb. It is not necessary that the drug should behave the same way in both animals and humans.

• Lactating women should inform the doctor before taking Nitrofurantoin as it can get into the child’s body through breast milk. Hence, lactating mothers should keep doctors updated regarding their breastfeeding status.

Things to Consider While Taking Nitrofurantoin:

• While taking Nitrofurantoin, patients are instructed to keep track of any sudden reactions in the form of breathing difficulty, rashes, swelling, paralysis, and collapse and need to report it to the concerned doctor at the earliest without fail.

• In case the patient tests positive for pregnancy while under Nitrofurantoin therapy, it is advised to get instructions from the doctor before proceeding with Nitrofurantoin. Any drug during pregnancy can potentially precipitate troubles in the growing child in the womb.

• If the person encounters signs of anemia like paleness and tiredness, immediately report it to the doctor because Nitrofurantoin is capable of inducing the destruction of the red cells in the circulation.

What Are the Instructions to Be Followed While on Nitrofurantoin?

• Strict adherence to the prescribed dosage is necessary to ensure the effectiveness of Nitrofurantoin in tackling UTIs. The patients should not modify the dose unless advised by the doctor.

• Self-medication without taking proper medical advice can precipitate grave complications.

• Nitrofurantoin can influence the glucose level in the urine, which, when tested while under Nitrofurantoin, elicits a false test result.

• Nitrofurantoin is advised to be taken after meals to reduce nauseous feelings.

What Are the Possible Side Effects of Nitrofurantoin?

• Nausea is the most frequently encountered side effect of Nitrofurantoin. The person experiences an extreme tendency to vomit and occasionally even vomit. In addition, the person also elicits loose stool, indigestion issues, flatulence (gas build-up), and pain in the abdominal area.

• Headache and other neurological troubles like vertigo, visual disparities, and eye pain are also reported in certain individuals. Occasionally, the person experiences an exhausted feeling.

• Respiratory issues are the potential side effects of Nitrofurantoin that are capable of precipitating grave breathing troubles.

• Nitrofurantoin projects a darker color to the urine. However, the urine regains its normal hue once Nitrofurantoin intake is stopped.

• Unexplained hair fall is routinely seen in association with Nitrofurantoin intake. The skin often develops allergic rashes with pus discharge. Occasionally, the facial structures swell up, posing challenges in breathing, and it entails prompt medical treatment.

• Nitrofurantoin intake often induces paleness over the skin due to the progressive destruction of the red cells from circulation, eventually leading to hemolytic anemia.

What Should Be Done if a Dose Is Missed?

If the patient forgets about the dose and misses one, then it is advised to take the pill as soon as the patient recalls. But if it is almost time for the subsequent dose, then the patient should disregard the missed dose and continue with the regime. Taking an additional pill to balance a forgotten dose may precipitate overdose issues, and hence, it is strongly advised not to take two pills altogether. Missing a dose of antibiotic significantly impacts the effectiveness of the pill, and therefore, proper care should be employed to take pills on time.

How Can One Treat Nitrofurantoin Overdose?

An acute overdose of Nitrofurantoin brings about long-standing vomiting, which facilitates the elimination of the medicine from the body. Excessive intake of fluid is advised to tackle the overdose so that the overdose medicine gets out of the body through urine. In certain patients, vomiting is induced to reduce the drug concentration in the body. In severe cases with remarkable overdose symptoms, dialysis should be initiated to facilitate the removal of the drug.

How to Store Nitrofurantoin?

• Nitrofurantoin is marketed in blister packaging, and it is instructed to store in the package till the time of intake.

• Out-of-date pills should not be taken, as they can cause other allergic reactions.

• The pill should be kept at room temperature within the range of 15 to 30 degrees Celsius. Temperature higher or lower than this range can cause changes in the constituents of the pill, which eventually influence its effectiveness.

• Make sure that the pills are placed such that it is inaccessible to kids.

For Doctors:

Indications

Nitrofurantoin is specifically indicated for

• Urinary tract infections (uncomplicated).

• Repeated UTIs (as prophylactic agents).

Contraindications

Nitrofurantoin is not safe for all patients; certain conditions and disorders make it unsuitable for certain individuals. Contraindications for Nitrofurantoin include the following:

• Patient with compromised renal functions, oliguria, and anuria.

• Pregnant patients approaching the delivery date (38 to 42 weeks) and undergoing labor pain.

• Patients with significantly low creatinine clearance rate (less than 60 milliliters per minute).

• Impaired liver functions and history of jaundice.

• Patients with a history of exaggerated sensitivity towards any of the components in Nitrofurantoin.

• Male patients who are suffering from prostatitis.

• Newborns and babies within one month of age.

Dosage and Administration

• Dose: 100 mg two times a day for a period of five days or seven days, considering the severity of the infection. When prescribed as a prophylactic agent, 50 mg or 100mg per day is sufficient.

• Dosage Forms: Suspension, tablet, capsules.

• Route of Administration: Nitrofurantoin is administered orally.

Pharmacology

Mechanism of Action:

Once Nitrofurantoin encounters a bacterial pathogen, the flavoproteins present within the bacterial cell pick up the drug. The bacterial flavoprotein then transforms the Nitrofurantoin into active metabolites. It is these metabolites that interrupt bacterial functions by attaching to the bacterial energy unit, the ribosome. Once the metabolites attach to the ribosome, the energy production within the bacterial cells gets completely hampered. In addition, it also checks bacterial enzymes required for the genetic material, eventually destroying the bacteria.

Pharmacodynamics:

Nitrofurantoin completely hampers the enzymatic activities in the bacterial cell. Ribosomal attachment of the Nitrofurantoin impacts bacterial energy production, and finally, it destroys the bacterial cell.

Pharmacokinetics:

• Absorption: Nitrofurantoin is present in two structural forms - macrocrystalline and monohydrate forms. Macrocrystalline form accounts for about 25 percent, and the larger crystal structure makes it difficult to get absorbed into the blood. However, it progressively breaks down into smaller fragments and facilitates absorption. While the monohydrate form, when acted upon by the intestinal enzymes, liberates Nitrofurantoin.

• Distribution: Nitrofurantoin does not achieve appreciable concentration in the blood. In the blood, it attaches to the plasma protein. However, significant concentration is detected in the urine. The urinary concentration further peaks when Nitrofurantoin is administered along with meals.

• Metabolism: Nitrofurantoin is chiefly metabolized in the liver by certain liver enzymes. A small fraction of the drug gets converted into amino furantoin form, while the major proportion remains unchanged.

• Elimination: A major proportion of Nitrofurantoin, about 90 percent, is removed from the body through urine. However, the elimination is also reported via the biliary route. In urine, almost 25 to 50 percent of the drug remains as such.

Drug Interactions

Nitrofurantoin elicits considerable reactions with certain drugs. Some of the notable drug interactions of Nitrofurantoin include:

• Simultaneous intake of Nitrofurantoin and certain antacids with magnesium trisilicate compounds checks the absorption of Nitrofurantoin.

• Nitrofurantoin, when taken along with uricosuric drugs like Sulfinpyrazone and Probenecid, brings about a remarkable hike in Nitrofurantoin concentration in the blood and, at the same time, diminishes the concentration in the urine. It may give rise to toxicity and, in addition, bring down the efficacy of the drug in tackling UTIs.

Warnings and Precautions Before Prescribing Nitrofurantoin

• Fatal to Newborn: Nitrofurantoin, when taken by pregnant women nearing the delivery date or while in labor pain, can induce hemolytic anemia in newborn babies. Hence, it is strictly not advised during the last weeks of pregnancy.

• Pulmonary Reactions: Nitrofurantoin carries the risk of precipitating grave reactions in the lung tissue. The reactions can be subacute, acute, or chronic. As these reactions can endanger a person’s life, patients should immediately stop drug intake and get medical help at the earliest.

• Clostridium Difficile-Associated Diarrhea: Nitrofurantoin administration may, at times, bring about Clostridium difficile-associated diarrhea (CDAD). It results from the preferential growth of difficile in the colonic region. If not given proper medical attention, it has the potential to precipitate fatal colitis.

• Hepatotoxicity: Long-term intake of Nitrofurantoin can injure the liver and impair its functions, eventually leading to jaundice, hepatitis, hepatic necrosis, and other liver-related issues. Assessing the liver enzymes periodically helps in keeping track of liver function. So that the injury can be detected at the early stage and prompt treatment can be initiated.

• Hemolytic Anemia: Inadequacy of the enzyme glucose-6 phosphate dehydrogenase is a potential stimulant for Nitrofurantoin to precipitate hemolytic anemia.

• Neuropathy: Nitrofurantoin can also precipitate peripheral neuropathy when taken for a longer period. Certain other disease conditions like diabetes, vitamin B deficiency, anemia, electrolyte imbalance, and renal impairment act as potential triggers when coupled with Nitrofurantoin.

• Incomplete Dose: Stopping the intake of Nitrofurantoin abruptly without completing the specified dosage regimenotably influences the effectiveness of the medicine and eventually results in Nitrofurantoin resistance.

Other Specifications

Nitrofurantoin During Pregnancy:

Nitrofurantoin is classified under category B, considering the pregnancy risk. Most of the nonclinical studies involving animals concluded that Nitrofurantoin could impact pregnancy when taken at the time of conception. However, Nitrofurantoin is routinely not advised during early pregnancy. It is strongly advised not to prescribe Nitrofurantoin to a pregnant lady approaching the last weeks of pregnancy as it poses the risk of hemolytic anemia in the baby.

Nitrofurantoin During Breastfeeding:

Studies have proven that Nitrofurantoin can pass into the newborn baby through the mother’s breast milk. Hence, lactating mothers are not advised to take Nitrofurantoin. At times, the drugs may be prescribed considering the mother’s need for the drug.