THE USUAL INITIAL DOSE BY MOUTH IN CHRONIC MUSCULOSKELETAL AND JOINT DISORDERS IS 25 MG TWO OR THREE TIMES DAILY INCREASED, IF REQUIRED, BY 25 TO 50 MG DAILY AT WEEKLY INTERVALS TO 150 TO 200 MG DAILY. TO ALLEVIATE NIGHT PAIN AND MORNING STIFFNESS, UP TO 100 MG OF THE TOTAL DAILY DOSE MAY BE GIVEN BY MOUTH, OR RECTALLY AS A SUPPOSITORY, ON RETIRING. ALTERNATIVELY, THE TOTAL DAILY DOSE MAY BE GIVEN RECTALLY AS 100 MG IN THE MORNING AND AT NIGHT. THE TOTAL DAILY COMBINED DOSE BY MOUTH AND BY RECTUM SHOULD NOT EXCEED 200 MG. IN ACUTE GOUT THE DAILY DOSE IS 150 TO 200 MG IN DIVIDED DOSES UNTIL ALL SYMPTOMS AND SIGNS SUBSIDE; IN DYSMENORRHOEA UP TO 75 MG DAILY HAS BEEN SUGGESTED.
ALTHOUGH NOT LICENSED IN THE UK FOR THE TREATMENT OF RHEUMATIC DISEASES SUCH AS JUVENILE IDIOPATHIC ARTHRITIS IN CHILDREN, THE BNFC SUGGESTS AN ORAL DOSE OF 0.5 TO 1 MG/KG TWICE DAILY IN THOSE AGED 1 MONTH TO 18 YEARS; HIGHER DOSES MAY BE REQUIRED.
MODIFIED-RELEASE PREPARATIONS OF INDOMETACIN ARE AVAILABLE FOR USE ONCE OR TWICE DAILY.
INDOMETACIN HAS BEEN USED TOPICALLY AS 0.5 OR 1% EYE DROPS TO PREVENT MIOSIS DURING CATARACT SURGERY; THE USUAL DOSE IS ONE DROP INSTILLED 4 TIMES DAILY, BEGINNING ON THE DAY BEFORE SURGERY, AND ONE DROP 45 MINUTES BEFORE SURGERY. THE EYE DROPS MAY THEN BE INSTILLED 4 TIMES DAILY FOR UP TO 10 TO 12 WEEKS POSTOPERATIVELY TO PREVENT CYSTOID MACULAR OEDEMA.
WHEN USED TO CLOSE PATENT DUCTUS ARTERIOSUS IN PREMATURE INFANTS INDOMETACIN SODIUM IS GIVEN AS THREE INTRAVENOUS DOSES AT 12- TO 24-HOUR INTERVALS; EACH DOSE SHOULD BE INFUSED OVER 20 TO 30 MINUTES. INDOMETACIN SODIUM INJECTION IS RECONSTITUTED WITH PRESERVATIVE-FREE SODIUM CHLORIDE 0.9% FOR INJECTION OR WATER FOR INJECTION; GLUCOSE SOLUTIONS SHOULD NOT BE USED (SEE INCOMPATIBILITY). THE DOSE OF INDOMETACIN SODIUM (EXPRESSED AS INDOMETACIN) DEPENDS UPON THE AGE OF THE NEONATE AND THE FOLLOWING DOSES HAVE BEEN SUGGESTED BASED UPON THE AGE AT THE FIRST DOSE: LESS THAN 48 HOURS OLD, 200 MICROGRAMS/KG INITIALLY FOLLOWED BY TWO FURTHER DOSES OF 100 MICROGRAMS/KG EACH; 2 TO 7 DAYS OLD, THREE DOSES OF 200 MICROGRAMS/KG EACH; OVER 7 DAYS OLD, 200 MICROGRAMS/KG INITIALLY FOLLOWED BY TWO FURTHER DOSES OF 250 MICROGRAMS/KG EACH. IF, 48 HOURS AFTER THIS COURSE OF THERAPY THE DUCTUS REMAINS OPEN OR RE-OPENS, A SECOND COURSE MAY BE USED, BUT IF THIS PRODUCES NO RESPONSE SURGERY MAY BE NECESSARY.
PREMATURE LABOUR.
THE MOST COMMON APPROACH TO POSTPONING PREMATURE LABOUR WITH DRUGS HAS HISTORICALLY BEEN WITH A SELECTIVE BETA2 AGONIST. HOWEVER, AS PROSTAGLANDINS HAVE A ROLE IN UTERINE CONTRACTION AND CERVICAL RIPENING AND DILATATION, PROSTAGLANDIN SYNTHETASE INHIBITORS SUCH AS INDOMETACIN HAVE ALSO BEEN USED. COMPARATIVE STUDIES HAVE DEMONSTRATED THAT INDOMETACIN AND RITODRINE ARE EQUALLY EFFECTIVE IN INHIBITING UTERINE CONTRACTIONS AND DELAYING DELIVERY IN PATIENTS IN PRETERM LABOUR WHO HAVE INTACT MEMBRANES AND IN WHOM THE GESTATIONAL AGE IS LESS THAN OR EQUAL TO 34 WEEKS. IN ONE STUDY AN INITIAL ORAL LOADING DOSE OF INDOMETACIN 50 MG WAS GIVEN, FOLLOWED BY 25 TO 50 MG ORALLY EVERY 4 HOURS UNTIL CONTRACTIONS STOPPED AND THEN BY A MAINTENANCE DOSE OF 25 MG EVERY 4 TO 6 HOURS. IN THE OTHER COMPARATIVE STUDY INDOMETACIN WAS GIVEN AS A 100-MG RECTAL SUPPOSITORY FOLLOWED BY 25 MG ORALLY EVERY 4 HOURS FOR 48 HOURS; IF REGULAR UTERINE CONTRACTIONS PERSISTED 1 TO 2 HOURS AFTER THE INITIAL SUPPOSITORY, AN ADDITIONAL 100-MG SUPPOSITORY WAS GIVEN BEFORE BEGINNING ORAL THERAPY. TERBUTALINE WAS GIVEN FOR MAINTENANCE THERAPY.
UNFORTUNATELY INDOMETACIN CAN CONSTRICT THE DUCTUS ARTERIOSUS WHICH MAY LEAD TO PULMONARY HYPERTENSION, AND HAS ALSO BEEN ASSOCIATED WITH BRONCHOPULMONARY DYSPLASIA, REDUCED VOLUME OF AMNIOTIC FLUID (OLIGOHYDRAMNIOS) AND POSSIBLE RENAL DAMAGE (SEE EFFECTS ON THE KIDNEYS )IN THE FETUS. ANOTHER COMPLICATION IS THAT PRENATAL INDOMETACIN EXPOSURE MAY INCREASE BOTH THE INCIDENCE AND SEVERITY OF PATENT DUCTUS ARTERIOSUS IN PREMATURE INFANTS, AS SHOWN BY THE INCREASED NEED FOR POST-NATAL INDOMETACIN THERAPY AND SURGICAL LIGATION IN SUCH INFANTS. SOME CONSIDER THE BENEFITS TO OUTWEIGH THE POTENTIAL RISKS, BUT INDOMETACIN IS GENERALLY RESERVED AS A SECOND-LINE TOCOLYTIC OR FOR COMBINATION WITH AN INTRAVENOUS TOCOLYTIC WHEN AN ADDITIVE EFFECT IS REQUIRED.