Nitrofurantoin Macrocrystals

These indications are based on manufacturer information for both originator and generic products. For product specific registered indications, please refer to product specific manufacturer information

Registered South African indications:

• Treatment and prevention of recurrence of uncomplicated lower urinary tract infections, e.g. pyelonephritis, pyelitis and cystitis

Contraindications 

South African recommendations

• Hypersensitivity to the active ingredient or any of its excipients 
• Anuria
• Oliguria
• Renal impairment 
• Full term pregnancy (in weeks 38-42) and during labour and delivery 
• Infants under three months of age because of the possibility of haemolytic anaemia due to immature enzyme systems (glutathione instability) 
• Glucose 6-phosphate dehydrogenase (G6PD) deficiency 
• Nursing mothers of infants with a deficiency of glucose 6-phosphate dehydrogenase 
• Acute porphyria 

Recommendations from other jurisdictions 

• Hypersensitivity to the active substance, other nitrofurans or to any of the excipients
• Patients suffering from renal dysfunction with an eGFR<45ml/min
• G6PD deficiency
• Acute porphyria
• In infants under three months of age as well as pregnant patients at term (during labour and delivery) because of the theoretical possibility of haemolytic anaemia in the foetus or in the newborn infant due to immature erythrocyte enzyme systems

Cautions

• Pregnancy (<38 weeks) (South African recommendations)
• Pregnancy (Not at term) (Recommendations from other jurisdictions)
• Renal impairment (eGFR≥45ml/min) (Recommendations from other jurisdictions)
• Hepatic impairment
• Elderly
• Parenchymal infections of unilaterally nonfunctioning kidney
• Upper urinary tract infections
• Pulmonary disease
• Neurological disorders
• Allergic diathesis
• Peripheral neuropathy or susceptibility to peripheral neuropathy
• Anaemia
• Diabetes mellitus
• Electrolyte imbalances
• Debilitating conditions
• Vitamin B (particularly folate) deficiency
• Prolonged use
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: cap

Dosages below include:

• South African Standard Treatment Guideline indications and dosages
• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

Infections caused by: Susceptible strains of Escherichia coli; Enterococci; Staphylococci; Citrobacter; Klebsiella and Enterobacter

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

South African Standard Treatment Guideline indications and dosages

Uncomplicated community-acquired cystitis
- If fosfomycin unavailable
Cystitis in pregnancy

• Oral (cap): 100mg, 6hrly; Treatment duration: 5 days
  (STG, Adult 2019; PHC 2020)

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South African registered indications and dosages

Treatment and prevention of recurrence of uncomplicated lower urinary tract infections, e.g. pyelonephritis, pyelitis and cystitis
- To treat acute urinary tract infections

• Oral (cap): 50-100mg, 6hrly with meals and at bedtime; Treatment duration: ≥7 days; Plus for ≥3 days after sterility of urine has been obtained

- To prevent recurrences

• Oral (cap): 50-100mg, dly

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It is not indicated for the treatment of associated renal, cortical or perinephric abscesses

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Continued infection indicates need for re-evaluation. Nitrofurantoin macrocrystals are highly soluble in urine, which may impart a brown colour

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Nitrofurantoin macrocrystals may be taken with food or milk (e.g. at mealtimes) to further minimise gastric upset

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Indications and dosages registered in other jurisdictions

Treatment and prophylaxis against acute or recurrent, uncomplicated lower urinary tract infections or pyelitis either spontaneous or following surgical procedures
- Acute uncomplicated urinary tract infections (UTIs)

• Oral (cap): 50mg, 6hrly; Treatment duration: 7 days

- Severe chronic recurrence (UTIs)

• Oral (cap): 100mg, 6hrly; Treatment duration: 7 days

- Long-term suppression

• Oral (cap): 50-100mg, dly

- Prophylaxis

• Oral (cap): 50mg, 6hrly for the duration of procedure and for 3 days thereafter

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This medicine should always be taken with food or milk. Taking nitrofurantoin macrocrystals with a meal improves absorption and is important for optimal efficacy

Paed. forms avail. in SA and covered in this monograph: cap

Paed. dosages below include:

• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

Infections caused by: Susceptible strains of Escherichia coli; Enterococci; Staphylococci; Citrobacter; Klebsiella and Enterobacter

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

South African registered indications and dosages

Treatment and prevention of recurrence of uncomplicated lower urinary tract infections, e.g. pyelonephritis, pyelitis and cystitis
- To treat acute urinary tract infections

Oral (cap)

• Younger than 3 months: Contraindicated
• Older than 3 months: 5-7mg/kg body mass, dly in 4 divided doses; Treatment duration: ≥7 days; Plus for ≥3 days after sterility of urine has been obtained

- To prevent recurrences

Oral (cap)

• Younger than 3 months: Contraindicated
• Older than 3 months: 1mg/kg body mass, dly for long term therapy

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It is not indicated for the treatment of associated renal, cortical or perinephric abscesses

---

Continued infection indicates need for re-evaluation. Nitrofurantoin macrocrystals are highly soluble in urine, which may impart a brown colour

---

Nitrofurantoin macrocrystals may be taken with food or milk (e.g. at mealtimes) to further minimise gastric upset

---

Indications and dosages registered in other jurisdictions

Treatment and prophylaxis against acute or recurrent, uncomplicated lower urinary tract infections or pyelitis either spontaneous or following surgical procedures
- Acute urinary tract infections

Oral (cap)

• Younger than 3 months: Contraindicated
• Older than 3 months: 3mg/kg/day, in 4 divided doses; Treatment duration: 7 days

- Suppressive therapy 

Oral (cap)

• Younger than 3 months: Contraindicated
• Older than 3 months: 1mg/kg, dly

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For children under 25kg body weight consideration should be given to the use of more suitable formulations available within jurisdiction

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This medicine should always be taken with food or milk. Taking nitrofurantoin macrocrystals with a meal improves absorption and is important for optimal efficacy

Pregnancy

South African recommendations

• At term (38-42 weeks) and during labour and delivery: Contraindicated
• <38 weeks: Caution
• Maternal side effects associated with nitrofurantoin macrocrystals may adversely affect the course of pregnancy
• Therefore, nitrofurantoin macrocrystals should be used at the lowest possible dose, only after careful assessment. Nitrofurantoin macrocrystals is contraindicated in weeks 38-42 of pregnancy, during labour and delivery

Recommendations in other jurisdictions

• At term (during labour and delivery): Contraindicated
• Not at term: Caution
• Animal studies with nitrofurantoin macrocrystals have shown no teratogenic effects
• Nitrofurantoin macrocrystals has been in extensive clinical use since 1952, and its suitability in human pregnancy has been well documented. However, as with all other drugs, the maternal side effects may adversely affect course of pregnancy. The drug should be used at the lowest dose as appropriate for a specific indication, only after careful assessment
• Nitrofurantoin is however contraindicated in infants under three months of age and in pregnant women during labour and delivery, because of the possible risk of haemolysis of the infants' immature red cells

Breastfeeding

South African recommendations

• When infant <3 months: Contraindicated
• Nitrofurantoin macrocrystals is contraindicated in infants <3 months old because of the possible risk of haemolysis of the infants’ immature red blood cells
• Therefore, nursing mothers should not breastfeed their infants while being treated with nitrofurantoin macrocrystals

Recommendations in other jurisdictions

• When infant <3 months: Contraindicated
• Breastfeeding an infant known or suspected to have an erythrocyte enzyme deficiency (including G6PD deficiency), must be temporarily avoided, since nitrofurantoin macrocrystals is detected in trace amounts in breast milk

Renal Impairment

South African recommendations

• Contraindicated

Recommendations in other jurisdictions

• eGFR≥45ml/min: Caution; no dose adjustment recommended
• eGFR<45ml/min: Contraindicated

Hepatic Impairment

• Caution; no dose adjustment recommended

Elderly

• Caution; no dose adjustment recommended

Porphyria Information

• Porphyrinogenic (P)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Peripheral neuropathy including optic neuritis (sensory and motor involvement)
• Depression
• Euphoria
• Confusion
• Psychotic reactions
• Nystagmus
• Vertigo
• Dizziness
• Asthenia
• Headache
• Drowsiness
• Benign intracranial hypertension
• Paresthesia

Cardiovascular Disorders

• Cardiac collapse
• Cyanosis

Respiratory Disorders

• Chronic pulmonary reactions
• Acute pulmonary reactions
• Subacute pulmonary reactions
• Cough
• Dyspnoea
• Permanent impairment of pulmonary function
• Pulmonary fibrosis (possible association with lupus-erythematous-like syndrome)
• Bronchiolitis obliterans organising pneumonia
• Diffuse interstitial pneumonitis

Gastrointestinal Disorders

• Nausea
• Emesis
• Abdominal pain
• Diarrhoea
• Sialadenitis
• Pancreatitis
• Anorexia

Hepatobiliary Disorders

• Hepatic impairment (which may be fatal)
• Hepatitis
• Cholestatic jaundice
• Chronic active hepatitis (fatalities have been reported)
• Autoimmune hepatitis
• Hepatic necrosis

Genitourinary Disorders

• Yellow or brown discolouration of urine
• Interstitial nephritis

Musculoskeletal Disorders

• Arthralgia

Skin and Subcutaneous Tissue Disorders

• Allergic skin reactions
• Angioneurotic oedema
• Cutaneous vasculitis
• Maculopapular eruptions
• Erythematous eruptions
• Eczematous eruptions
• Urticaria
• Rash
• Pruritus
• Exfoliative dermatitis
• Erythema multiforme
• Stevens-Johnson Syndrome
• Transient alopecia
• Drug rash with eosinophilia and systemic symptoms (DRESS syndrome)

Immune, Blood and Lymphatic System Disorders

• Aplastic anaemia
• Eosinophilia
• Agranulocytosis
• Leucopenia
• Granulocytopenia
• Haemolytic anaemia
• Thrombocytopenia
• Megaloblastic anaemia
• Glucose-6-phosphate dehydrogenase deficiency anaemia
• Acute porphyria
• Superinfections by fungi or resistant organisms such as Pseudomonas
• Lupus-like syndrome with pulmonary reaction
• Anaphylaxis
• Drug fever
• Fever
• Chills

Others

• False-positive urinary glucose

• Agents that delay gastric emptying
• Magnesium trisilicate
• Probenecid
• Sulphinpyrazone
• Carbonic anhydrase inhibitors
• Quinolone antibiotics
• Oestrogen contraceptives
• Typhoid vaccine

Other interactions

• Interference with some tests for glucose in urine (Reducing substances- susceptible to false-positive urinary glucose)

None routine. Specific cases may require

• Renal function
• Hepatic function
• Respiratory examination
• Full blood count

Additional observations

• Signs of pulmonary reaction
• Signs of numbness or tingling of extremities

 

Nitrofurantoin is reduced by various bacterial enzymes to reactive intermediates which bind to bacterial ribosomes and inhibit several bacterial enzymes involved in the synthesis of DNA, RNA and other metabolic enzymes.

Spectrum of activity: Some gram-positive aerobic microorganisms such as Enterococcus species, Staphylococcus aureus, Coagulase-negative staphylococci (including Staphylococcus epidermidis and Staphylococcus saprophyticus), Streptococcus agalactiae, Viridans group streptococci, Some aerobic gram-negative microorganisms such as Citrobacter koseri* Citrobacter freundii*, Escherichia coli, Klebsiella oxytoca*

*In-vitro data are available, but their clinical significance is unknown

Capsule 50mg

• Macrodantin (Pharmacare) originator
• Cipladantin 50 ( Cipla Medpro)
• Turanto 50 ( Macleods Pharmaceuticals)

Capsule 100mg

• Macrodantin (Pharmacare) originator
• Cipladantin 100 ( Cipla Medpro)
• Turanto 100 ( Macleods Pharmaceuticals)