Nitrofurantoin is an orally administered medicine that is used to treat uncomplicated infections of the bladder. It is not indicated for complicated infections and infections of the kidneys or upper urinary tract.

Nitrofurantoin Uses:

• Treatment of acute uncomplicated Cystitis:

  • Nitrofurantoin monohydrate/ macrocrystals (Macrobid):

    • Treatment of acute uncomplicated cystitis caused by sensitive microbes  Escherichia coil or Staphylococcus saprophyticus in patients ≥12 years of age.

  • Nitrofurantoin macrocrystals (Furadantin, Macrodantin):

    • Treatment of acute uncomplicated cystitis when caused by susceptible strains of E. coli/enterococci, Staphylococcus aureus, and certain susceptible strains of Klebsiella and Enterobacter species

  • Limitations of use:

    • It is not indicated for the treatment of pyelonephritis or perinephric abscess.

• Prophylaxis of recurrent Cystitis:

  • Nitrofurantoin macrocrystals (Furadantin, Macrodantin):

    • It is used for chronic suppression of recurrent urinary tract infections

Nitrofurantoin dose in Adults

Note:

• Nitrofurantoin is chemically available in the form of nitrofurantoin macrocrystals and nitrofurantoin monohydrate.
• Two different preparations are available in the US A combination of nitrofurantoin monohydrate and nitrofurantoin macrocrystals (Macrobid), which is typically prescribed as b.i.d daily for treating acute infections and a preparation that consists solely of nitrofurantoin macrocrystals (Furadantin, Macrodantin), which is given q.i.d daily for treating acute infections. It is recommended to administer with food to improve absorption.

Nitrofurantoin dose for the treatment of acute uncomplicated Cystitis or acute simple cystitis:

Note: Different empiric agents should be used with suspected pyelonephritis/ patients who had nitrofurantoin course in the last 3 months/ patients with microbes documented resistance to nitrofurantoin in the last 3 months.

• Nitrofurantoin monohydrate/macrocrystals (Macrobid):

  • 100 mg per oral b.i.d daily;
  • treat females for 5 days and males for 7 days.

• Nitrofurantoin macrocrystals (Furadantin, Macrodantin):

  • 50 to 100 mg per oral every 6 hourly,
  • Treat females for 5 days and males for 7 days.

• Note:

  • The recommended duration of therapy with this formulation is based on the recommendation for the nitrofurantoin monohydrate/macrocrystal formulation as well as the expert opinion.

Nitrofurantoin Dose in the prophylaxis of recurrent Cystitis:

Note: In non-pregnant women with recurrent uncomplicated cystitis despite non-antimicrobial preventative measures, prophylaxis may be taken into consideration. Since there is no established therapy, the selection of an antibiotic is based on local patterns of resistance and patient-specific criteria (such as prior efficacy and cost). Long term therapy (>6 months) of nitrofurantoin can lead to diffuse interstitial pneumonitis, pulmonary fibrosis, chronic hepatitis, and neuropathy.

• Nitrofurantoin Continuous prophylaxis:

  • Nitrofurantoin monohydrate/macrocrystals (Macrobid) (off-label use):

    • 100 mg per orally once daily at bedtime.

  • Nitrofurantoin macrocrystals (Furadantin, Macrodantin):

    • 50–100 mg taken orally once daily before bed.

• Postcoital prophylaxis: Females with cystitis due to sexual intercourse.

  • Nitrofurantoin monohydrate/macrocrystals (Macrobid) (off-label use):

    • A single oral dose of 100 mg should be given within two hours of sexual activity.

  • Nitrofurantoin macrocrystals (Furadantin, Macrodantin):

    • 50 to 100 mg per oral as a single dose taken within 2 hours of sexual intercourse.

Nitrofurantoin dose in Children

Nitrofurantoin dose for the treatment of Urinary tract infection (UTI):

• Furadantin, Macrodantin:

  • 5 to 7 mg/kg per mouth per day split every six hours for seven days, or for at least three days following the collection of sterile urine;
  • The maximum dose is 100 mg/dose

• Fixed dosing: Furadantin oral suspension:

  • 7 to <12 kg:

    • 12.5 mg every 6 hours

  • 12 to < 22 kg:

    • 25 mg every 6 hours

  • 22 to <31 kg:

    • 37.5 mg every 6 hours

  • 31 to <42 kg:

    • 50 mg every 6 hours

  • ≥42 kg:

    • 50 to 100 mg every 6 hours

• Macrobid (macrocrystal/monohydrate):

  • Adolescents: 100 mg taken orally every 12 hours for seven days

Nitrofurantoin Dose in the prophylaxis of UTI:

• Furadantin, Macrodantin:

  • Oral dose of 1 to 2 mg/kg/day either as a single dose (at bedtime) or divided into two doses per day.
  • The daily dose cap is set at 100 mg.

• Note:

  • In infants and children <24 months, prophylaxis should only be considered for those with grade III-V reflux or with recurrent febrile UTI.

Pregnancy Risk Factor B (contraindicated at term)

• It can cross the placental barrier.
• Recent studies that evaluated nitrofurantoin usage during pregnancy and the development birth defects have shown mixed results.
• After the use of this product during the last 30 days, there was an increase in neonatal jaundice.
• Pregnancy may lead to a decrease in maternal serum concentrations.
• It can also be used during pregnancy.
• You should limit your use of the first trimester to situations in which there are no other therapies.
• It should only be used for the most severe cases of confirmed infection.
• It isContraindicatedat term (38-42 weeks gestation/ during labor/ delivery/ or when labor is imminent because of hemolytic anemia.
• Alternate antibiotics should also be used during pregnancy in the event of G6PD deficiency.

Use during breastfeeding:

• It comes out of breast milk.
• Due to the potential for hemolytic anemia, nitrofurantoin therapy is not recommended for children under 1 month old.
• Although the risk of developing hemolytic anemia from breastfeeding infants exposed to the drug via breastmilk is theoretically higher, there have been no reports.
• Depending on how important breastfeeding is to the mother, the manufacturer advises deciding whether to cease it or to stop taking the medication.
• According to the World Health Organization (WHO), breastfeeding is possible for healthy full-term babies. The drug can be monitored for any adverse effects like jaundice or hemolysis.
• Breastfeeding neonates or babies less than one month should be avoided by women who use nitrofurantoin.
• Breastfeeding should be stopped in cases of G6PD deficiency. This is true for infants of all ages (in countries like the Eastern Mediterranean, African and Southeast Asian populations).
• One mother saw two infants who were breastfed and observed a decrease in milk concentration. (Dosage, duration, and relationship to breastfeeding not given).
• Breast milk can cause bowel changes that are not dose-related.
• It is important to monitor infants for gastrointestinal problems.

Dose adjusmtent in renal disease:

• Creatinine clearance ≥60 mL/minute:

  • The manufacturer's labelling does not mention dosage modifications.

• Creatinine clearance<60 mL/minute:

  • For the short-term treatment of uncomplicated acute cystitis in individuals with an estimated glomerular filtration rate or creatinine clearance of 30 to 60 mL/minute, limited evidence indicate that nitrofurantoin is safe and efficacious.
    According to the Beers Criteria, patients under 65 with a creatinine clearance of less than 30 mL/min should not use this medication.

• Manufacturer's labeling:

  • Dosing is based on product labeling and may not reflect current clinical practice. Use is contraindicated.

Dose adjustment in iver disease:

There are no dosage adjustments provided in the manufacturer's labeling. It is contraindicated in patients with history of cholestatic jaundice or liver dysfunction due to the drug.

Side Effects of Nitrofurantoin:

• Central Nervous System:

  • Headache

• Endocrine & Metabolic:

  • Increased Serum Phosphate

• Gastrointestinal:

  • Nausea
  • Flatulence

• Hematologic & Oncologic:

  • Decreased Hemoglobin
  • Eosinophilia

• Hepatic:

  • Increased Serum Alanine Aminotransferase
  • Increased Serum Aspartate Aminotransferase

Uncommon side effects of nitrofurantoin:

• Cardiovascular:

  • Bundle Branch Block
  • Chest Pain
  • ECG Changes
  • Nonspecific T Wave On ECG
  • Vasculitis

• Central Nervous System:

  • Bulging Fontanel
  • Confusion
  • Depression
  • Drug Fever
  • Peripheral Neuropathy
  • Pseudotumor Cerebri
  • Psychotic Reaction
  • Vertigo

• Dermatologic:

  • Eczematous Rash
  • Erythema Multiforme
  • Erythematous Maculopapular Rash
  • Exfoliative Dermatitis
  • Maculopapular Rash
  • Skin Rash
  • Stevens-Johnson Syndrome

• Gastrointestinal:

  • Anorexia
  • Clostridioides
  • Clostridium Difficile Colitis
  • Pancreatitis
  • Sialadenitis
  • Vomiting

• Genitourinary:

  • Urine Discoloration

• Hematologic & Oncologic:

  • Agranulocytosis
  • Aplastic Anemia
  • Glucose-6-Phosphate Dehydrogenase Deficiency Anemia
  • Granulocytopenia
  • Hemolytic Anemia
  • Leukopenia
  • Megaloblastic Anemia
  • Methemoglobinemia
  • Thrombocytopenia

• Hepatic:

  • Cholestatic Jaundice
  • Chronic Active Hepatitis
  • Hepatic Necrosis
  • Hepatitis

• Hypersensitivity:

  • Anaphylaxis
  • Angioedema
  • Hypersensitivity Reaction

• Infection:

  • Superinfection

• Neuromuscular & Skeletal:

  • Arthralgia
  • Asthenia
  • Lupus-Like Syndrome
  • Myalgia

• Ophthalmic:

  • Nystagmus

• Respiratory:

  • Acute Pulmonary Reaction
  • Chronic Pulmonary Reaction
  • Cough
  • Cyanosis
  • Dyspnea
  • Dyspnea On Exertion
  • Interstitial Pneumonitis
  • Pleural Effusion
  • Pulmonary Fibrosis
  • Pulmonary Infiltrates

Contraindication to Nitrofurantoin:

• Anuria, oliguria, and serious renal function impairment (creatinine clearance of 60 mL/min or noticeably elevated blood creatinine) are some of these.
• Hypersensitivity to any medication or ingredient in the formula prior use history of liver disease or cholestatic jaundice

Notice:

• The manufacturer's contraindication for patients with creatinine clearance of 60 mL/minute has been contested in the literature.
• A different creatinine clearance threshold might be taken into consideration, according to limited evidence [Ref].
• The medication shouldn't be taken in pregnant women who are term (38–42 weeks gestation), in labour, giving birth, or when labour is about to start because it has the potential to cause hemolytic anaemia because of immature erythrocyte protein/glutathione stability.
• You should avoid it if you are younger than one month.

Warnings and precautions

• Optic neuritis:

  • There have been some reports of optic neuritis.

• Peripheral neuropathy:

  • It is rare for it to cause peripheral neuropathy. Anemia, renal impairment (creatinine clearance60 mL/minute), DM and vitamin B deficiencies, as well as debilitating diseases and electrolyte abnormalities, increase the risk.

• Toxicity in the lungs:

  • If you have severe, persistent, or subacute pulmonary reactions (usually within 6 months of treatment), it is important to stop therapy.
  • On X-ray, it is important to monitor for symptoms such as malaise and shortness of breathing, cough, fever, diffuse intrastitial pneumonitis, fibrosis, or other signs.

• Superinfection

  • The possibility of fungal or bacterial superinfections, such as Clostridium difficile-associated diarrhea (CD) and pseudomembranous collitis, may occur over a longer period of time. This has been reported >2 months after antibiotic treatment.

• Specific groups

  • Use caution when necessary in cases such as liver impairment, renal impairment, or G6PD deficiency.

Nitrofurantoin: Drug Interaction

Monitoring parameters:

Monitoring for:

• Signs of pulmonary reaction
• peripheral numbness or tingling
• complete blood count
• liver function tests, and
• renal function tests with long-term use.

How to administer Nitrofurantoin?

It should be given orally with food to improve absorption and decrease side effects. suspension may be mixed with water, milk, or fruit juice. Shake suspension well before use.

Mechanism of action of Nitrofurantoin:

• Flavoproteins from Bacteria cause a decrease in nitrofurantoin to reactive intermediaries that inactivate/alter bacterial ribosomal protein, leading to inhibition of protein and aerobic energy metabolism.
• At therapeutic doses, nitrofurantoin can be used to kill bacteria in the urine. Because of its mechanism of action, nitrofurantoin is rarely able to cause bacterial resistance.
• The multiple simultaneous mutations required to target macromolecules are usually fatal to the bacteria.

Absorption: Macrocrystalline forms are more easily absorbed and cause less digestive distress. Protein binding: 60% to 90% Metabolism: occurs in body tissues (except plasma) metabolize 60% of the drug to inactive metabolites Bioavailability: Increased with food by up to 40% Half-life elimination: 20minutes to 1 hour; prolonged with renal impairment Excretion: Suspension: occurs in urine (~40%) and feces (small amounts) as metabolites and unchanged drug Macrocrystals: Urine (20% to 25% as unchanged drug)

Nitrofurantoin Brand Names (International):

• Furadantin
• Macrobid
• Macrodantin
• Auro-Nitrofurantoin
• Macrobid
• PMS-Nitrofurantoin
• TEVA-Nitrofurantoin
• Colifuran
• Furadantin
• Furadantin Retard
• Furadantina
• Furadantine
• Furadantine MC
• Furadantine-MC
• Furadin
• Furadina
• Furadonin
• Furadonins
• Furanpur
• Furantoina
• Furitex
• Furolin
• Macrobid
• Macrodantin
• Macrodantina
• Macrodantina XR
• Macrodin
• Macrofuran
• Mepafuran
• Nifuran
• Nifurantin
• Nifuryl
• Nifutoin
• Nintoin
• Ninur
• Nitrofurantoin ”Dak”
• Nitrofurantoin-ratiopharm
• Orafuran
• Piyeloseptyl
• Rantoin
• Siraliden
• Urantoin
• Uro-Tablinen
• Urobak
• Urocure
• Urofuran
• Uroin
• Urontin
• Urotoina
• Uvamin

Nitrofurantoin Brand Names in Pakistan: