Nitrofurantoin (Nitrofurantoin) - Side Effects and Adverse Reactions

ADVERSE REACTIONS:

In clinical trials of nitrofurantoin monohydrate/macrocrystals, the most frequent clinical adverse events that were reported as possibly or probably drug-related were nausea (8%), headache (6%), and flatulence (1.5%). Additional clinical adverse events reported as possibly or probably drug-related occurred in less than 1% of patients studied and are listed below within each body system in order of decreasing frequency:

Gastrointestinal: Diarrhea, dyspepsia, abdominal pain, constipation, emesis

Neurologic: Dizziness, drowsiness, amblyopia

Respiratory: Acute pulmonary hypersensitivity reaction (see WARNINGS)

Allergic: Pruritus, urticaria

Dermatologic: Alopecia

Miscellaneous: Fever, chills, malaise

The following additional clinical adverse events have been reported with the use of nitrofurantoin:

Gastrointestinal: Sialadenitis, pancreatitis. There have been sporadic reports of pseudomembranous colitis with the use of nitrofurantoin. The onset of pseudomembranous colitis symptoms may occur during or after antimicrobial treatment. (See WARNINGS.)

Neurologic: Peripheral neuropathy, which may become severe or irreversible, has occurred. Fatalities have been reported. Conditions such as renal impairment (creatinine clearance under 60 mL per minute or clinically significant elevated serum creatinine), anemia, diabetes mellitus, electrolyte imbalance, vitamin B deficiency, and debilitating diseases may increase the possibility of peripheral neuropathy. (See WARNINGS.)

Asthenia, vertigo, and nystagmus also have been reported with the use of nitrofurantoin.

Benign intracranial hypertension (pseudotumor cerebri), confusion, depression, optic neuritis, and psychotic reactions have been reported rarely. Bulging fontanels, as a sign of benign intracranial hypertension in infants, have been reported rarely.

Respiratory:

CHRONIC, SUBACUTE, OR ACUTE PULMONARY HYPERSENSITIVITY REACTIONS MAY OCCUR WITH THE USE OF NITROFURANTOIN.

CHRONIC PULMONARY REACTIONS GENERALLY OCCUR IN PATIENTS WHO HAVE RECEIVED CONTINUOUS TREATMENT FOR SIX MONTHS OR LONGER. MALAISE, DYSPNEA ON EXERTION, COUGH, AND ALTERED PULMONARY FUNCTION ARE COMMON MANIFESTATIONS WHICH CAN OCCUR INSIDIOUSLY. RADIOLOGIC AND HISTOLOGIC FINDINGS OF DIFFUSE INTERSTITIAL PNEUMONITIS OR FIBROSIS, OR BOTH, ARE ALSO COMMON MANIFESTATIONS OF THE CHRONIC PULMONARY REACTION. FEVER IS RARELY PROMINENT.

THE SEVERITY OF CHRONIC PULMONARY REACTIONS AND THEIR DEGREE OF RESOLUTION APPEAR TO BE RELATED TO THE DURATION OF THERAPY AFTER THE FIRST CLINICAL SIGNS APPEAR. PULMONARY FUNCTION MAY BE IMPAIRED PERMANENTLY, EVEN AFTER CESSATION OF THERAPY. THE RISK IS GREATER WHEN CHRONIC PULMONARY REACTIONS ARE NOT RECOGNIZED EARLY.

In subacute pulmonary reactions, fever and eosinophilia occur less often than in the acute form. Upon cessation of therapy, recovery may require several months. If the symptoms are not recognized as being drug-related and nitrofurantoin therapy is not stopped, the symptoms may become more severe.

Acute pulmonary reactions are commonly manifested by fever, chills, cough, chest pain, dyspnea, pulmonary infiltration with consolidation or pleural effusion on x-ray, and eosinophilia. Acute reactions usually occur within the first week of treatment and are reversible with cessation of therapy. Resolution often is dramatic. (See WARNINGS.)

Changes in EKG (e.g., non-specific ST/T wave changes, bundle branch block) have been reported in association with pulmonary reactions.

Cyanosis has been reported rarely.

Hepatic: Hepatic reactions, including hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis, occur rarely. (See WARNINGS.)

Allergic: Lupus-like syndrome associated with pulmonary reaction to nitrofurantoin has been reported. Also, angioedema; maculopapular, erythematous, or eczematous eruptions; anaphylaxis; arthralgia; myalgia; drug fever; and chills have been reported. Hypersensitivity reactions represent the most frequent spontaneously-reported adverse events in worldwide postmarketing experience with nitrofurantoin formulations.

Dermatologic: Exfoliative dermatitis and erythema multiforme (including Stevens-Johnson syndrome) have been reported rarely.

Hematologic: Cyanosis secondary to methemoglobinemia has been reported rarely.

Miscellaneous: As with other antimicrobial agents, superinfections caused by resistant organisms, e.g., Pseudomonas species or Candida species, can occur.

In clinical trials of nitrofurantoin monohydrate/macrocrystals, the most frequent laboratory adverse events (1 to 5%), without regard to drug relationship, were as follows: eosinophilia, increased AST (SGOT), increased ALT (SGPT), decreased hemoglobin, increased serum phosphorus. The following laboratory adverse events also have been reported with the use of nitrofurantoin: glucose-6-phosphate dehydrogenase deficiency anemia (see WARNINGS), agranulocytosis, leukopenia, granulocytopenia, hemolytic anemia, thrombocytopenia, megaloblastic anemia. In most cases, these hematologic abnormalities resolved following cessation of therapy. Aplastic anemia has been reported rarely.

REPORTS OF SIDE EFFECTS / ADVERSE REACTIONS RELATED TO NITROFURANTOIN

Possible Nitrofurantoin side effects / adverse reactions in 71 year old female

Reported by a individual with unspecified qualification from United States on 2007-01-19

Patient: 71 year old female weighing 108.4 kg (238.5 pounds)

Reactions: Myalgia, Arthralgia

Suspect drug(s):
Nitrofurantoin
    Dosage: see image
    Administration route: Oral
    Indication: Urinary Tract Infection

Nitrofurantoin
    Dosage: see image
    Administration route: Oral
    Indication: Urinary Tract Infection

Possible Nitrofurantoin side effects / adverse reactions in 27 year old female

Reported by a health professional (non-physician/pharmacist) from Canada on 2007-02-09

Patient: 27 year old female

Reactions: Blood Pressure Increased, Haemoptysis, Hypercapnia, Blood Lactate Dehydrogenase Increased, Neutrophilia, Microcytic Anaemia, Pitting Oedema, Drug Exposure During Pregnancy, Chest Pain, Hypoxia, Leukocytosis, Hyperdynamic Precordium, RED Blood Cell Sedimentation Rate Increased, Pneumonitis

Adverse event resulted in: hospitalization

Suspect drug(s):
Nitrofurantoin

Other drugs received by patient: Prednisone TAB

Possible Nitrofurantoin side effects / adverse reactions in 81 year old female

Reported by a health professional (non-physician/pharmacist) from France on 2007-03-23

Patient: 81 year old female

Reactions: Interstitial Lung Disease

Adverse event resulted in: hospitalization

Suspect drug(s):
Nitrofurantoin
    Administration route: Oral
    Indication: Cystitis
    Start date: 2001-01-01
    End date: 2005-07-26

Singulair
    Administration route: Oral
    Indication: Asthma

Other drugs received by patient: Lorazepam; Paroxetine Hydrochloride

Possible Nitrofurantoin side effects / adverse reactions in 53 year old male

Reported by a physician from India on 2007-04-02

Patient: 53 year old male weighing 55.0 kg (121.0 pounds)

Reactions: Dyspepsia, Pyrexia, Candidiasis, Leukopenia

Adverse event resulted in: life threatening event, hospitalization

Suspect drug(s):
Nitrofurantoin
    Dosage: see image
    Administration route: Oral
    Indication: Urinary Tract Infection
    Start date: 2007-02-20
    End date: 2007-02-26

Nitrofurantoin
    Dosage: see image
    Administration route: Oral
    Indication: Urinary Tract Infection
    Start date: 2007-02-27
    End date: 2007-03-06

Possible Nitrofurantoin side effects / adverse reactions in 28 year old female

Reported by a individual with unspecified qualification from United Kingdom on 2007-04-16

Patient: 28 year old female

Reactions: Vomiting, Malaise, Drug Exposure During Pregnancy, Nausea, Headache, Abortion Spontaneous

Adverse event resulted in: hospitalization

Suspect drug(s):
Nitrofurantoin

Possible Nitrofurantoin side effects / adverse reactions in 86 year old female

Reported by a individual with unspecified qualification from United States on 2007-05-07

Patient: 86 year old female

Reactions: Scapula Fracture, Weight Decreased, Dysphagia, Dyspnoea, Wrist Fracture, Pain in Extremity, Rash, Fall, Abdominal Pain Upper, Oedema Peripheral, Laryngeal Inflammation, Laryngotracheal Oedema

Adverse event resulted in: hospitalization

Suspect drug(s):
Nitrofurantoin

Possible Nitrofurantoin side effects / adverse reactions in 47 year old female

Reported by a physician from United States on 2007-05-10

Patient: 47 year old female weighing 83.9 kg (184.6 pounds)

Reactions: Blood Bilirubin Increased, Blood Bilirubin Unconjugated Increased, Chills, Pain, Urticaria, Headache, Constipation, Fatigue, Oedema, Blood Alkaline Phosphatase Increased, Nausea, Hepatitis Acute, Haemorrhoids, Drug Hypersensitivity, Alanine Aminotransferase Increased, Jaundice Cholestatic, Eosinophil Count Increased, Discomfort, Hepatic Enzyme Increased, Tremor, Faeces Pale, Flushing, Aspartate Aminotransferase Increased, Urine Colour Abnormal, Ocular Icterus, Bilirubin Conjugated Increased, Influenza Like Illness

Suspect drug(s):
Estradiol
    Dosage: 0.05 mg, qd, transdermal
    Indication: Oestrogen Replacement Therapy
    Start date: 2006-07-01
    End date: 2006-08-01

Nitrofurantoin
    Dosage: 100 mg, oral
    Administration route: Oral
    Indication: Cystitis
    Start date: 2006-08-11
    End date: 2006-08-13

Possible Nitrofurantoin side effects / adverse reactions in 68 year old male

Reported by a consumer/non-health professional from United States on 2007-05-15

Patient: 68 year old male weighing 111.1 kg (244.4 pounds)

Reactions: Dyspnoea, Pulmonary Embolism, Deep Vein Thrombosis, Blood Glucose Increased

Adverse event resulted in: hospitalization

Suspect drug(s):
Nitrofurantoin

Other drugs received by patient: Metoprolol Succinate; Benazepril (Benazepril); Buspirone HCL; Actos; Exelon; Zocor; Bicitra (Citric Acid, Sodium Citrate)

Possible Nitrofurantoin side effects / adverse reactions in 65 year old female

Reported by a pharmacist from Netherlands on 2007-06-12

Patient: 65 year old female

Reactions: Phaeochromocytoma, Neck Pain, Flank Pain, Headache, Hyperhidrosis, Blood Pressure Fluctuation, Hypertension, Nervousness

Adverse event resulted in: hospitalization

Suspect drug(s):
Nitrofurantoin

Other drugs received by patient: Ascal Cardio (Carbasalate Calcium); Labetalol HCL; Micardisplus (Hydrochlorothiazide, Telmisartan); Seretide Diskus (Fluticasone Propionate, Salmeterol Xinafoate); Atrovent (Ipratroprium Bromide)

Possible Nitrofurantoin side effects / adverse reactions in 84 year old female

Reported by a physician from United States on 2007-06-15

Patient: 84 year old female

Reactions: Blood Bilirubin Increased, Jaundice, Alanine Aminotransferase Increased, Aspartate Aminotransferase Increased, Oedema Peripheral, Hepatic Failure, Liver Disorder

Suspect drug(s):
Nitrofurantoin
    Dosage: see image
    Start date: 2003-01-14
    End date: 2003-08-01

Nitrofurantoin
    Dosage: see image
    Start date: 2004-09-09
    End date: 2005-11-09

Other drugs received by patient: Cardia; Cozaar; Coumadin; Lipitor

Possible Nitrofurantoin side effects / adverse reactions in 68 year old male

Reported by a physician from United States on 2007-06-19

Patient: 68 year old male weighing 111.1 kg (244.4 pounds)

Reactions: Pulmonary Embolism, Blood Glucose Increased, Deep Vein Thrombosis

Adverse event resulted in: hospitalization

Suspect drug(s):
Nitrofurantoin

Other drugs received by patient: Metoprolol Tartrate; Benazepril (Benazepril); Buspirone HCL; Actos; Exelon; Zocor; Bicitra (Citric Acid, Sodium Citrate)

Possible Nitrofurantoin side effects / adverse reactions in 81 year old male

Reported by a individual with unspecified qualification on 2007-06-21

Patient: 81 year old male

Reactions: Anaemia, Duodenal Ulcer

Suspect drug(s):
Dipyridamole

Nitrofurantoin

Salicylic Acid
    Dosage: low-dose

Possible Nitrofurantoin side effects / adverse reactions in 78 year old female

Reported by a individual with unspecified qualification from United Kingdom on 2007-06-21

Patient: 78 year old female

Reactions: Nephritis Interstitial, Renal Impairment, Condition Aggravated

Adverse event resulted in: hospitalization

Suspect drug(s):
Nitrofurantoin

Possible Nitrofurantoin side effects / adverse reactions in 86 year old female

Reported by a consumer/non-health professional from United States on 2007-06-27

Patient: 86 year old female

Reactions: Abdominal Pain, Weight Decreased, Wrist Fracture, Upper Limb Fracture, Pain, Fall, Abdominal Pain Upper, Pancreatic Disorder, Oesophagitis, Dyspepsia, Oedema Peripheral, Laryngotracheal Oedema, Scapula Fracture, Dyspnoea, Dysphagia, Pancreatic Atrophy, Pain in Extremity, Rash, Pancreatic Insufficiency

Adverse event resulted in: hospitalization

Suspect drug(s):
Nitrofurantoin

Possible Nitrofurantoin side effects / adverse reactions in 34 year old female

Reported by a consumer/non-health professional from United States on 2007-07-11

Patient: 34 year old female weighing 59.0 kg (129.7 pounds)

Reactions: Vomiting, Nausea, Drug Hypersensitivity, Urticaria, Swollen Tongue, Hyperhidrosis, Hyperventilation, Auricular Swelling, Oedema Peripheral

Adverse event resulted in: hospitalization

Suspect drug(s):
Nitrofurantoin

Possible Nitrofurantoin side effects / adverse reactions in 68 year old male

Reported by a physician from United States on 2007-07-25

Patient: 68 year old male weighing 111.1 kg (244.4 pounds)

Reactions: Pancreatic Carcinoma, Coagulopathy, Sudden Death, Pulmonary Embolism, Blood Glucose Increased, Deep Vein Thrombosis

Adverse event resulted in: death, hospitalization

Suspect drug(s):
Nitrofurantoin

Other drugs received by patient: Metoprolol Tartrate; Benazepril (Benazepril); Buspirone HCL; Actos; Exelon; Zocor; Bicitra (Citric Acid, Sodium Citrate)

Possible Nitrofurantoin side effects / adverse reactions in 67 year old female

Reported by a physician from Australia on 2007-10-08

Patient: 67 year old female

Reactions: Weight Decreased, Hepatitis Cholestatic, Jaundice, Chromaturia, Decreased Appetite

Adverse event resulted in: hospitalization

Suspect drug(s):
Celecoxib
    Administration route: Oral
    Indication: Osteoporosis
    End date: 2003-02-20

Dothiepin Hydrochloride
    Administration route: Oral
    Indication: Depression
    End date: 2003-02-20

Estrogens, Conjugated
    Administration route: Oral
    Indication: Menopausal Symptoms
    End date: 2003-02-20

Fosamax
    Administration route: Oral
    End date: 2003-02-20

Nitrofurantoin
    Administration route: Oral
    Indication: Urinary Tract Disorder
    End date: 2003-02-20

Other drugs received by patient: Levothyroxine Sodium

Possible Nitrofurantoin side effects / adverse reactions in 97 year old female

Reported by a pharmacist from United States on 2007-10-10

Patient: 97 year old female

Reactions: Confusional State, Compression Fracture, Post Procedural Complication, Delirium, Pulmonary Fibrosis

Adverse event resulted in: hospitalization

Suspect drug(s):
Nitrofurantoin
    Dosage: 100mg bid po
    Administration route: Oral
    Indication: Escherichia Urinary Tract Infection

Nitrofurantoin
    Dosage: 50mg tid po
    Administration route: Oral
    Indication: Escherichia Urinary Tract Infection

Other drugs received by patient: Fentanyl; Percocet; Tramadol HCL; Morphine; Prednisone; Aspirin; Zoloft; Lasix; K-DUR 10; Colace; Nexium; Lactulose; Diovan; Senokot; Oscal; NTP

Possible Nitrofurantoin side effects / adverse reactions in 82 year old female

Reported by a pharmacist from United States on 2007-10-10

Patient: 82 year old female weighing 67.1 kg (147.7 pounds)

Reactions: Dyspnoea, Anaphylactic Reaction

Adverse event resulted in: life threatening event

Suspect drug(s):
Nitrofurantoin