Monograph: |
PLEASE NOTE PROTHIONAMIDE IS NOT LICENSED IN THE UK.
PROTHIONAMIDE IS A THIOAMIDE, AND IS CONSIDERED TO BE INTERCHANGEABLE WITH ETHIONAMIDE (CURRENTLY NOT AVAILABLE IN THE UK).
PHARMACOKINETICS
PROTHIONAMIDE IS READILY ABSORBED FROM THE GASTRO-INTESTINAL
TRACT AND PRODUCES PEAK PLASMA CONCENTRATIONS ABOUT 2 HOURS
AFTER A DOSE BY MOUTH. IT IS WIDELY DISTRIBUTED THROUGHOUT
BODY TISSUES AND FLUIDS, INCLUDING THE CSF. PROTHIONAMIDE IS
METABOLISED TO THE ACTIVE SULPHOXIDE AND OTHER INACTIVE ME-
TABOLITES AND LESS THAN 1% OF A DOSE APPEARS IN THE URINE AS
UNCHANGED DRUG.
USES AND ADMINISTRATION
PROTHIONAMIDE IS A THIOAMIDE DERIVATIVE CONSIDERED TO BE IN-
TERCHANGEABLE WITH ETHIONAMIDE . COMPLETE CROSS-RE-
SISTANCE OCCURS BETWEEN THE TWO DRUGS. PROTHIONAMIDE HAS
BEEN ADMINISTERED BY MOUTH IN DOSES SIMILAR TO THOSE USED FOR
ETHIONAMIDE. IT HAS ALSO BEEN ADMINISTERED AS RECTAL SUPPOSI-
TORIES; PROTHIONAMIDE HYDROCHLORIDE HAS BEEN GIVEN INTRAVE-
NOUSLY. LIKE ETHIONAMIDE. IT HAS GENERALLY BEEN REPLACED BY
LESS TOXIC ANTIMYCOBACTERIALS.
DOSAGE
ADULT & PAEDIATRIC DOSES ARE THE SAME PER KG.
ADULTS: 15-20MG/KG (MAX. 1G) ONCE DAILY (ORAL).
ONCE DAILY DOSING IS PREFERRED TO MAXIMISE PEAK LEVELS, PARTICULARLY FOR DAILY DOSES ?750MG. CONSIDER TWICE DAILY DOSING IF PATIENTS ARE UNABLE TO TOLERATE ONCE DAILY REGIMENS.
CHILDREN: 15-20MG/KG (MAX. 1G) ONCE DAILY (ORAL).
ONCE DAILY DOSING IS PREFERRED TO MAXIMISE PEAK LEVELS, PARTICULARLY FOR DAILY DOSES ?750MG. CONSIDER TWICE DAILY DOSING IF PATIENTS ARE UNABLE TO TOLERATE ONCE DAILY REGIMENS.
PROTHIONAMIDE SHOULD BE TAKEN WITH OR AFTER MEALS TO REDUCE GASTROINTESTINAL ADVERSE EFFECTS. MOST PATIENTS ALSO REQUIRE GRADUAL DOSE ESCALATION, I.E. FOR ADULTS: INITIALLY 250MG ONCE A DAY, INCREASING BY 250MG EVERY 3 TO 5 DAYS.
ALL PATIENTS MUST BE PRESCRIBED PYRIDOXINE WHILST RECEIVING PROTHIONAMIDE. THE USUAL ADULT DOSE RANGES FROM 50 TO 100MG DAILY, UP TO 50MG PER 250MG OF PROTHIONAMIDE.
PREPARATIONS
ORAL: 250MG TABLETS (UNLICENSED MEDICINE).
DRUG LEVEL MONITORING
Β· NOT REQUIRED.
ADVERSE EFFECTS
COMMON:
HEPATIC: TRANSIENT INCREASES IN LFTS.
GASTROINTESTINAL: NAUSEA, VOMITING, DIARRHOEA, ANOREXIA, EXCESSIVE SALIVATION, METALLIC TASTE, STOMATITIS, AND ABDOMINAL PAIN.
SERIOUS:
HEPATIC: ACUTE HEPATITIS (RARE).
NEUROLOGICAL (MAYBE INCREASED IN COMBINATION WITH CYCLOSERINE): DIZZINESS, ENCEPHALOPATHY, PERIPHERAL NEUROPATHY.
OPHTHALMIC: OPTIC NEURITIS (RARE).
PSYCHIATRIC: PSYCHOTIC DISTURBANCES, DEPRESSION.
METABOLIC: GYNAECOMASTIA, HYPOGLYCAEMIA, HYPOTHYROIDISM.
ADVERSE EFFECTS: MONITORING
TFTS: 3 MONTHLY (IF BEING GIVEN IN COMBINATION WITH PAS INCREASE TO MONTHLY).
BLOOD GLUCOSE SHOULD BE MONITORED REGULARLY IN PATIENTS WITH DIABETES (RISK OF HYPOGLYCAEMIA).
ROUTINE TESTS AS PER GENERIC MDR-TB TREATMENT MONITORING GUIDELINES .
INTERACTONS
CYCLOSERINE: POSSIBLE INCREASED RISK OF NEUROTOXICITY.
ISONIAZID: INCREASED SERUM CONCENTRATIONS.
P-AMINOSALICYLIC ACID: INCREASED RISK OF HYPOTHYROIDISM, POSSIBLE INCREASED RISK OF HEPATOXICITY.
RIFAMPICIN: INCREASED RISK OF HEPATOXICITY.
THIS INFORMATION IS NOT INCLUSIVE OF ALL DRUG INTERACTIONS. PLEASE DISCUSS WITH A PHARMACIST.
CONTRA-INDICATIONS & CAUTIONS
CONTRAINDICATIONS:
HYPERSENSITIVITY: TO ETHIONAMIDE OR PROTHBIONAMIDE.
SEVERE LIVER DISEASE: DUE TO RISK OF FURTHER HEPATOTOXICITY.
PREGNANCY.
PORPHYRIA.
CAUTIONS:
RENAL DISEASE: REDUCE DOSE IN SEVERE RENAL IMPAIRMENT.
BREAST-FEEDING.
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