Drugs List

Therapeutic Indications

Uses

Tuberculosis - resistant to first-line treatment
Urinary tract infection

Adjunctive treatment of active pulmonary and extra-pulmonary tuberculosis (including renal disease) where first line therapies have failed.

Urinary tract infections caused by gram-positive and gram-negative bacteria when conventional therapy has failed.

Contraindications

Alcoholism
Depression
Epileptic disorder
Psychosis
Severe anxiety
Severe renal impairment

Precautions and Warnings

Acute porphyria
Breastfeeding
Mild renal impairment
Pregnancy

Advise patient drowsiness may affect ability to drive or operate machinery
Consult national/regional policy on the use of anti-infectives
Determine susceptibility to tuberculosis prior to treatment
Take cultures for sensitivity testing before and regularly during treatment
Monitor blood concentration - should not exceed 30mg/litre
Monitor drug blood levels weekly in renal impairment or if high dose
Monitor for occurrence of anaemia
Monitor renal, hepatic and haematological parameters
Discontinue or reduce dose if allergic dermatitis occurs
Discontinue or reduce dose if CNS toxicity occurs
Advise patient to avoid alcohol during treatment

Toxicity is usually associated with blood levels greater than 30 mg/l. The therapeutic index for cycloserine is low.

Monitor blood levels and reduce dose for patients with renal dysfunction, for individuals receiving doses above 500 mg daily and in patients with signs and symptoms of toxicity. Adjust dose to keep blood levels below 30 mg/l.

Discontinue or reduce dose if allergic dermatitis or symptoms of CNS toxicity (e.g. convulsions, psychosis, somnolence, depression, confusion, hyperreflexia) occur. Patients on more than 500 mg daily should be closely monitored for these symptoms. Anticonvulsant drugs or sedatives may be effective in controlling symptoms of CNS toxicity. The value of pyridoxine in preventing CNS toxicity from cycloserine has not been proven.

Determine susceptibility of organism to cycloserine and concurrent therapy in tuberculosis prior to treatment.

Patients taking cycloserine with anti-tuberculosis therapy may develop vitamin B12 deficiency, folic acid deficiency, megaloblastic anaemia and sideroblastic anaemia. If this occurs investigations and treatment is recommended.

Cycloserine has been associated with clinical exacerbations of porphyria.

Pregnancy and Lactation

Pregnancy

Use cycloserine with caution in pregnancy.

Briggs suggests cycloserine should not be withheld because of pregnancy but notes that limited data prevents a complete risk assessment. Schaefer suggests that single case reports do not prove a high teratogenic risk. The manufacturer suggests cycloserine should only be given in pregnancy if clearly needed.

It is unknown whether cycloserine can cause foetal harm or affect reproductive capability. Concentrations in foetal blood approach those found in the serum. Limited data (3 pregnancies) on exposure to cycloserine during first trimester do not suggest adverse foetal effects.

Animal studies in rats revealed no teratogenic effects given in doses up to 100 mg/kg daily.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use cycloserine with caution in breastfeeding.

Schaefer suggests a decision whether to limit breastfeeding during cycloserine therapy should be taken. Hale suggests because of the potentially significant levels of cycloserine in human milk, breastfeeding should be withheld for 24 hours. The Drugs and Lactation Database (LactMed) suggests if use is required, it is not reason to discontinue breastfeeding but that exclusively breastfed infants should be monitored, possibly with measurement of serum levels. The manufacturer suggests to take a decision of discontinuing cycloserine or discontinuing breastfeeding, taking into account the benefit of therapy to the patient.

Cycloserine is excreted into breast milk. Concentrations of cycloserine in the mother's milk approach those found in the serum.

No adverse effects were observed in breastfed infants whose mothers were receiving cycloserine.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Aggression
Allergic reaction
Coma
Confusion
Congestive cardiac failure
Convulsions
Depression
Disorientation
Drowsiness
Dysarthria
Headache
Hyperreflexia
Increase in aminotransferase level
Irritability
Megaloblastic anaemia
Memory loss
Paraesthesia
Paresis
Personality change
Psychosis
Rash
Seizures
Somnolence
Suicidal tendencies
Tremor
Vertigo

Presentation

Oral formulations of cycloserine

Drugs List

Therapeutic Indications

Uses

Tuberculosis - resistant to first-line treatment
Urinary tract infection

Adjunctive treatment of active pulmonary and extra-pulmonary tuberculosis (including renal disease) where first line therapies have failed.

Urinary tract infections caused by gram-positive and gram-negative bacteria when conventional therapy has failed.

Dosage

Before treatment is initiated, cultures should be taken and the susceptibility of the organism to cycloserine determined. For the treatment of tuberculosis, sensitivity to other antituberculosis agents should be demonstrated.

Adults

Children

Patients with Renal Impairment

Contraindications

Alcoholism
Depression
Epileptic disorder
Psychosis
Severe anxiety
Severe renal impairment

Precautions and Warnings

Acute porphyria
Breastfeeding
Mild renal impairment
Pregnancy

Advise patient drowsiness may affect ability to drive or operate machinery
Consult national/regional policy on the use of anti-infectives
Determine susceptibility to tuberculosis prior to treatment
Take cultures for sensitivity testing before and regularly during treatment
Monitor blood concentration - should not exceed 30mg/litre
Monitor drug blood levels weekly in renal impairment or if high dose
Monitor for occurrence of anaemia
Monitor renal, hepatic and haematological parameters
Discontinue or reduce dose if allergic dermatitis occurs
Discontinue or reduce dose if CNS toxicity occurs
Advise patient to avoid alcohol during treatment

Toxicity is usually associated with blood levels greater than 30 mg/l. The therapeutic index for cycloserine is low.

Monitor blood levels and reduce dose for patients with renal dysfunction, for individuals receiving doses above 500 mg daily and in patients with signs and symptoms of toxicity. Adjust dose to keep blood levels below 30 mg/l.

Discontinue or reduce dose if allergic dermatitis or symptoms of CNS toxicity (e.g. convulsions, psychosis, somnolence, depression, confusion, hyperreflexia) occur. Patients on more than 500 mg daily should be closely monitored for these symptoms. Anticonvulsant drugs or sedatives may be effective in controlling symptoms of CNS toxicity. The value of pyridoxine in preventing CNS toxicity from cycloserine has not been proven.

Determine susceptibility of organism to cycloserine and concurrent therapy in tuberculosis prior to treatment.

Patients taking cycloserine with anti-tuberculosis therapy may develop vitamin B12 deficiency, folic acid deficiency, megaloblastic anaemia and sideroblastic anaemia. If this occurs investigations and treatment is recommended.

Cycloserine has been associated with clinical exacerbations of porphyria.

Pregnancy and Lactation

Pregnancy

Use cycloserine with caution in pregnancy.

Briggs suggests cycloserine should not be withheld because of pregnancy but notes that limited data prevents a complete risk assessment. Schaefer suggests that single case reports do not prove a high teratogenic risk. The manufacturer suggests cycloserine should only be given in pregnancy if clearly needed.

It is unknown whether cycloserine can cause foetal harm or affect reproductive capability. Concentrations in foetal blood approach those found in the serum. Limited data (3 pregnancies) on exposure to cycloserine during first trimester do not suggest adverse foetal effects.

Animal studies in rats revealed no teratogenic effects given in doses up to 100 mg/kg daily.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use cycloserine with caution in breastfeeding.

Schaefer suggests a decision whether to limit breastfeeding during cycloserine therapy should be taken. Hale suggests because of the potentially significant levels of cycloserine in human milk, breastfeeding should be withheld for 24 hours. The Drugs and Lactation Database (LactMed) suggests if use is required, it is not reason to discontinue breastfeeding but that exclusively breastfed infants should be monitored, possibly with measurement of serum levels. The manufacturer suggests to take a decision of discontinuing cycloserine or discontinuing breastfeeding, taking into account the benefit of therapy to the patient.

Cycloserine is excreted into breast milk. Concentrations of cycloserine in the mother's milk approach those found in the serum.

No adverse effects were observed in breastfed infants whose mothers were receiving cycloserine.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Aggression
Allergic reaction
Coma
Confusion
Congestive cardiac failure
Convulsions
Depression
Disorientation
Drowsiness
Dysarthria
Headache
Hyperreflexia
Increase in aminotransferase level
Irritability
Megaloblastic anaemia
Memory loss
Paraesthesia
Paresis
Personality change
Psychosis
Rash
Seizures
Somnolence
Suicidal tendencies
Tremor
Vertigo

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: December 2016

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.

Summary of Product Characteristics: Cycloserine 250 mg capsules. King Pharmaceuticals Ltd. Revised November 2015.

NICE - Evidence Services
Available at: www.nice.org.uk
Last accessed: 23 June 2017.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Cycloserine. Last revised: September 7, 2013.
Last accessed: December 9, 2016.