indomethacin

Absorption: Well absorbed after oral administration in adults; incomplete oral absorption in neonates.

Distribution: Crosses the blood-brain barrier.

Protein Binding: 99%.

Metabolism/Excretion: Mostly metabolized by the liver.

Half-Life: Neonates <2 wk: 20 hr; Neonates >2 wk: 11 hr; Adults: 2.6–11 hr.

Time/Action Profile ⬆ ⬇

ROUTE	ONSET	PEAK	DURATION
PO (analgesic)	30 min	0.5–2 hr	4–6 hr
PO-ER (analgesic)	30 min	unknown	4–6 hr
PO (anti-inflammatory)	up to 7 days	1–2 wk	4–6 hr
PO-ER (anti-inflammatory)	up to 7 days	1–2 wk	4–6 hr
IV (closure of PDA)	up to 48 hr	unknown	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Known alcohol intolerance (suspension);
Cross-sensitivity may exist with other NSAIDs, including aspirin;
Active GI bleeding;
Ulcer disease;
Proctitis or recent history of rectal bleeding;
Intraventricular hemorrhage;
Thrombocytopenia;
Coronary artery bypass graft surgery
;
Recent MI
;
HF;
OB: Avoid use after 30 wk gestation (may cause premature closure of fetal ductus arteriosus);
Pedi: ↑risk of necrotizing enterocolitis and bowel perforation in premature infants with PDA.

Use Cautiously in:

Severe renal impairment;
Severe hepatic impairment;
Cardiovascular disease or risk factors for cardiovascular disease (may ↑ risk of serious cardiovascular thrombotic events, MI, and stroke, especially with prolonged use or use of higher doses)
;
History of long duration of NSAID use, smoking, alcohol use, advanced liver disease, coagulopathy, or poor general health (↑ risk of GI bleeding)
;
History of peptic ulcer disease and/or GI bleeding
;
Bleeding tendency or concurrent anticoagulant therapy
;
Seizure disorders;
Hypertension;
OB: Use at or after 20 wk gestation may cause fetal renal impairment leading to oligohydramnios and, possibly neonatal renal impairment; if treatment is necessary between 20 wk and 30 wk gestation, limit use to the lowest effective dose and shortest duration possible;
Geri:
Appears on Beers list. ↑ risk GI bleeding or peptic ulcer disease in older adults. Avoid chronic use unless other alternatives are not effective and the patient can take a gastroprotective agent; avoid short-term use in combination with oral or parenteral corticosteroids, anticoagulants, or antiplatelet agents unless other alternatives are not effective and the patient can take a gastroprotective agent
.

Adv. Reactions/Side Effects ⬆ ⬇

CV: edema, HF, hypertension, MI

Derm: EXFOLIATIVE DERMATITIS, GENERALIZED BULLOUS FIXED DRUG ERUPTION, rash, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN)

EENT: blurred vision, tinnitus

Endo: IVhypoglycemia

F and E: hyperkalemia, IVhyponatremia

GI: constipation, dyspepsia, nausea, vomiting, discomfort, POGI BLEEDING, GI PERFORATION, GI ULCERATION, HEPATOTOXICITY, necrotizing enterocolitis, PANCREATITIS

GU: cystitis, hematuria, renal failure

Hemat: blood dyscrasias, prolonged bleeding time, thrombocytopenia

Local: phlebitis at IV site

Neuro: dizziness, drowsiness, headache, psychic disturbances, STROKE

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND SERIOUS SKIN REACTIONS)

Interactions ⬆ ⬇

Drug-drug:

Concurrent use with aspirin may ↓ effectiveness.
↑risk of GI bleeding with anticoagulants, aspirin, clopidogrel, ticagrelor, prasugrel, corticosteroids, fibrinolytics, SNRIs, or SSRIs
.
Chronic use of acetaminophen↑ risk of adverse renal reactions.
May ↓ effectiveness of diuretics or antihypertensives.
May ↑ hypoglycemia from insulins or oral hypoglycemic agents.
May ↑ risk of toxicity from lithium or zidovudine (avoid concurrent use with zidovudine).
↑risk of toxicity from methotrexate.
Probenecid↑ risk of toxicity from indomethacin.
↑risk of adverse hematologic reactions with antineoplastics or radiation therapy.
↑risk of nephrotoxicity with cyclosporine.
Concurrent use with potassium-sparing diuretics may result in hyperkalemia.
May ↑ levels of digoxin, methotrexate, lithium, and aminoglycosides when used IV in neonates.

Drug-Natural Products:

↑bleeding risk with anise, arnica, chamomile, clove, dong quai, feverfew, garlic, ginger, ginkgo, and Panax ginseng.

Route/Dosage ⬆ ⬇

Anti-inflammatory

PO (Adults ): Arthritis (immediate release): 25–50 mg 2–4 times daily (max dose = 200 mg/day). A single bedtime dose of 100 mg may alternatively be used; Arthritis (extended release): 75 mg once or twice daily (max dose = 150 mg/day). Gout: 100 mg initially, followed by 50 mg 3 times daily for relief of pain; then ↓ further.
PO (Children >2 yr): 1–2 mg/kg/day in 2–4 divided doses (not to exceed 4 mg/kg/day or 150–200 mg/day).

PDA Closure

IV (Neonates ): Treatment: 0.2 mg/kg initially, then 2 subsequent doses at 12–24 hr intervals of 0.1 mg/kg if age <48 hr at time of initial dose; 0.2 mg/kg if 2–7 days at initial dose; 0.25 mg/kg if age >7 days at initial dose. Prophylaxis: 0.1–0.2 mg/kg initially, then 0.1 mg/kg every 12–24 hr for 2 doses.

Availability ⬆ ⬇

(Generic available)

Capsules: 25 mg; 50 mg
Extended-release capsules: 75 mg
Oral suspension fruit mint, pineapple, coconut, mint flavors: 25 mg/5 mL
Powder for injection: 1 mg/vial
Rectal suppository: 50 mg; 100 mg

Assessment ⬆ ⬇

Monitor for rhinitis, asthma, and urticaria. Patients who have asthma, aspirin-induced allergy, and nasal polyps are at ↑ risk for developing hypersensitivity reactions.
Assess for SJS, TEN, and generalized bullous fixed drug eruption. Discontinue indomethacin at 1st sign of rash and treat as indicated.
Monitor BP during initiation and periodically thereafter.
Arthritis: Assess limitation of movement and pain; note type, location, and intensity before and 1–2 hr after administration.
PDA: Monitor respiratory status, HR, BP, echocardiogram, and heart sounds routinely throughout therapy.
- Monitor intake and output. Fluid restriction is usually instituted throughout therapy.
Acute pain: Assess type, location, and intensity of pain prior to and 2 hr (peak) following administration.

Lab Test Considerations:

Evaluate BUN, serum creatinine, CBC, potassium , and liver function tests periodically in patients receiving prolonged therapy.
- May alter blood glucose values.
- May ↓ hemoglobin, hematocrit, leukocytes, platelets, and CCr. Bleeding time may be prolonged for several days after last dose.
- May cause ↑ in urine glucose and protein concentrations.

Implementation ⬆ ⬇

If prolonged therapy is used, dose should be ↓ to the lowest level that controls symptoms to minimize risk of cardiovascular thrombotic events.
PO: Administer after meals, with food, or with antacids to ↓ GI irritation. DNC: Do not break, crush, or chew sustained-release capsules.
- Shake suspension before administration. Do not mix with antacid or any other liquid.

IV Administration:

IV Push: Reconstitution: Reconstitute with 1–2 mL of preservative-free 0.9% NaCl or sterile water. Reconstitute immediately before use and discard any unused solution. Do not dilute further or admix. Concentration: 0.5–1 mg/mL.
Rate: Administer over 20–30 min. Do not administer via umbilical catheter into vessels near the superior mesenteric artery, as these can cause vasoconstriction and compromise blood flow to the intestines. Do not administer intra-arterially.
Y-Site Compatibility:
- aminophylline
- ascorbic acid
- atropine
- bumetanide
- caffeine citrate
- cefazolin
- cefotaxime
- cefoxitin
- ceftazidime
- ceftriaxone
- cefuroxime
- chloramphenicol
- cisplatin
- clindamycin
- cyanocobalamin
- cyclosporine
- dexamethasone
- digoxin
- enalaprilat
- ephedrine
- epoetin alfa
- fentanyl
- fluconazole
- folic acid
- furosemide
- ganciclovir
- heparin
- hydrocortisone
- imipenem/cilastatin
- insulin regular
- ketorolac
- lidocaine
- mannitol
- metoclopramide
- metoprolol
- multivitamins
- nafcillin
- nitroglycerin
- nitroprusside
- penicillin G
- pentobarbital
- phenobarbital
- phytonadione
- potassium chloride
- procainamide
- sodium bicarbonate
- theophylline
Y-Site Incompatibility:
- amikacin
- atracurium
- aztreonam
- benztropine
- buprenorphine
- butorphanol
- calcium chloride
- calcium gluconate
- cefotetan
- chlorpromazine
- dactinomycin
- dantrolene
- daunorubicin
- diazepam
- diazoxide
- diphenhydramine
- dobutamine
- dopamine
- doxycycline
- epinephrine
- erythromycin
- esmolol
- etoposide
- famotidine
- gentamicin
- glycopyrrolate
- haloperidol
- hydralazine
- isoproterenol
- labetalol
- levofloxacin
- magnesium sulfate
- meperidine
- midazolam
- minocycline
- morphine
- nalbuphine
- norepinephrine
- ondansetron
- oxytocin
- paclitaxel
- pantoprazole
- papaverine
- pentamidine
- phenylephrine
- phenytoin
- prochlorperazine
- promethazine
- propranolol
- protamine
- pyridoxine
- succinylcholine
- sufentanil
- thiamine
- tobramycin
- trimethoprim/sulfamethoxazole
- vancomycin
- vasopressin
- verapamil

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Advise patient to take this medication with a full glass of water and to remain in an upright position for 15–30 min after administration.
May cause drowsiness or dizziness. Advise patient to avoid driving or other activities requiring alertness until response to medication is known.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other medications. Avoid concurrent use of alcohol, aspirin and other NSAIDs.
Caution patient to wear sunscreen and protective clothing to prevent photosensitivity reactions.
Advise patient to inform health care provider of medication regimen before treatment or surgery.
Inform patient of ↑ risk of MI and stroke. Use lowest effective dose for shortest time. Advise patient to notify health care provider immediately if signs and symptoms (shortness of breath or trouble breathing, chest pain, weakness in one part or side of body, slurred speech, swelling of the face or throat) occur.
Advise patient to notify health care provider promptly if signs or symptoms of GI toxicity (abdominal pain, black stools) occur.
Instruct patient to notify health care provider immediately if signs and symptoms of hepatotoxicity (nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, flu-like symptoms), rash, itching, chills, fever, muscle aches, visual disturbances, weight gain, edema, or persistent headache occurs.
Rep: May cause fetal harm. Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding. Advise women to avoid indomethacin in the 3rd trimester of pregnancy (after 29 wk); may cause premature closure of the fetal ductus arteriosus. Use of indomethacin after 20 wk may cause fetal renal dysfunction leading to oligohydramnios. May cause temporary infertility in women.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇