Notolac

A synthetic opioid that is used as the hydrochloride. It is an opioid analgesic that is primarily a mu-opioid agonist. It has actions and uses similar to those of morphine. It also has a depressant action on the cough center and may be given to control intractable cough associated with terminal lung cancer. Notolac is also used as part of the treatment of dependence on opioid drugs, although prolonged use of methadone itself may result in dependence. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1082-3)

Carefully consider the potential benefits and risks of Notolac Tromethamine and other treatment options before deciding to use Notolac. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.

Acute Pain in Adult Patients

Notolac Tromethamine is indicated for the short-term (≤5 days) management of moderately severe acute pain that requires analgesia at the opioid level, usually in a postoperative setting. Therapy should always be initiated with IV or IM dosing of Notolac Tromethamine, and oral Notolac Tromethamine is to be used only as continuation treatment, if necessary.

The total combined duration of use of Notolac Tromethamine injection and oral Notolac Tromethamine is not to exceed 5 days of use because of the potential of increasing the frequency and severity of adverse reactions associated with the recommended doses. Patients should be switched to alternative analgesics as soon as possible, but Notolac Tromethamine therapy is not to exceed 5 days.

Notolac Tromethamine injection has been used concomitantly with morphine and meperidine and has shown an opioid-sparing effect. For breakthrough pain, it is recommended to supplement the lower end of the Notolac Tromethamine injection dosage range with low doses of narcotics prn, unless otherwise contraindicated. Notolac Tromethamine injection and narcotics should not be administered in the same syringe.

Notolac (Notolac) is a nonsteroidal anti-inflammatory drug (NSAID). Notolac works by reducing hormones that cause inflammation and pain in the body.

Notolac is used short-term (5 days or less) to treat moderate to severe pain.

Notolac may also be used for purposes not listed in this medication guide.

Carefully consider the potential benefits and risks of Notolac tromethamine tablets and other treatment options before deciding to use Notolac tromethamine tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals. In adults, the combined duration of use of IV or IM dosing of Notolac tromethamine and Notolac tromethamine tablets is not to exceed 5 days. In adults, the use of Notolac tromethamine tablets is only indicated as continuation therapy to IV or IM dosing of Notolac tromethamine.

Transition from IV or IM dosing of Notolac tromethamine (single- or multiple-dose) to multiple-dose Notolac tromethamine tablets:

Patients age 17 to 64: 20 mg PO once followed by 10 mg q4 to 6 hours prn not > 40 mg/day

Patients age ≥ 65, renally impaired, and/or weight < 50 kg (110 lbs): 10 mg PO once followed by 10 mg q4 to 6 hours prn not > 40 mg/day

Note:

Oral formulation should not be given as an initial dose.

Use minimum effective dose for the individual patient.

Do not shorten dosing interval of 4 to 6 hours.

Total duration of treatment in adult patients: the combined duration of use of IV or IM dosing of Notolac tromethamine and Notolac tromethamine tablets is not to exceed 5 days.

The following table summarizes Notolac tromethamine tablet dosing instructions in terms of age group:

See also:
What is the most important information I should know about Notolac?

Notolac Tromethamine is contraindicated in patients with previously demonstrated hypersensitivity to Notolac Tromethamine.

Notolac Tromethamine is contraindicated in patients with active peptic ulcer disease, in patients with recent gastrointestinal bleeding or perforation and in patients with a history of peptic ulcer disease or gastrointestinal bleeding.

Notolac Tromethamine should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients.

Notolac Tromethamine is contraindicated as prophylactic analgesic before any major surgery.

Notolac Tromethamine is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery.

Notolac Tromethamine is contraindicated in patients with advanced renal impairment or in patients at risk for renal failure due to volume depletion.

Notolac Tromethamine is contraindicated in labor and delivery because, through its prostaglandin synthesis inhibitory effect, it may adversely affect fetal circulation and inhibit uterine musculature, thus increasing the risk of uterine hemorrhage.

Notolac Tromethamine inhibits platelet function and is, therefore, contraindicated in patients with suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis and those at high risk of bleeding.

Notolac Tromethamine is contraindicated in patients currently receiving aspirin or NSAIDs because of the cumulative risks of inducing serious NSAID-related adverse events.

The concomitant use of Notolac Tromethamine and probenecid is contraindicated.

The concomitant use of Notolac Tromethamine and pentoxifylline is contraindicated.

Notolac Tromethamine injection is contraindicated for neuraxial (epidural or intrathecal) administration due to its alcohol content.

Use Notolac spray as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Notolac spray comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Notolac spray refilled.
• Do not take Notolac spray by mouth. Use in your nose only.
• Before you use each bottle for the first time, you must prime it. Remove the clear plastic cover and the blue plastic safety clip. Hold the bottle at arm's length away from you. Using your index and middle fingers on the top of the bottle and your thumb on the bottom of the bottle, press down evenly and release the pump 5 times. The bottle is now ready to use.
• To use this nose spray, gently blow your nose. Sit up straight or stand and tilt your head forward slightly. Place the tip of the spray container into the nose. Be sure to point the container away from the center of your nose. Breathe gently through the nostril and squeeze the spray container. If your dose requires 2 sprays, repeat the process for your other nostril. Replace the clear plastic cover after each use.
• Do NOT use Notolac spray for more than 5 days. Notolac spray is not for the treatment of mild to moderate or chronic pain (eg, headache).
• Avoid contact with the eyes. If you get Notolac spray in your eyes, rinse it out with water. If eye irritation persists for more than 1 hour, contact your doctor.
• Each bottle contains 1 day's supply of Notolac spray. Discard each bottle within 24 hours of opening it, even if it still contains some unused medicine.
• If you miss a dose of Notolac spray and you are taking it regularly, take it as soon as possible. If it is almost time for the next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Notolac spray.

Use: Labeled Indications

Pain, moderate to moderately severe: Short-term (up to 5 days) management of moderate to moderately severe pain in adults that requires analgesia at the opioid level.

Off Label Uses

Migraine

Data from a prospective, randomized, double-blind, double-dummy, placebo and active comparator, crossover, non-inferiority trial suggests that intranasal Notolac may be beneficial for acute abortive treatment of migraine in patients with a history of episodic migraines for at least 1 year.

See also:
What other drugs will affect Notolac?

Should be used with caution in patients undergoing anticoagulant therapy and use must be strictly monitored. Combination of Notolac tromethamine and other NSAIDs is not recommended because it would increase the risk of side effects.

Warfarin: Protein-binding of warfarin may be decreased slightly from 99.5-99.3%. It does not significantly change the pharmacokinetics or pharmacodynamics profile. Protein-binding of Notolac does not change.

Heparin: Prolongs average bleeding time (placebo: 5.1 min; heparin: 6 min; heparin + Notolac: 6.4 min).

Digoxin: Protein-binding of digoxin and Notolac does not change.

Salicylate: Protein-binding of Notolac was decreased from 99.2-97.5% which would represent a potential 2-fold increase in plasma concentrations of unbound drug.

Ibuprofen, Naproxen, Piroxicam, Acetaminophen, Phenytoin and Tolbutamide: Protein-binding does not change.

Furosemide: Reduced diuretic response 20% (mean sodium and urinary output decreased 17%).

Probenecid: Results in decreased clearance of Notolac and significant increases in Notolac plasma levels (Total AUC increased ±3-folds from 5.4-17.8 mcg/hr/mL, terminal t_½ increase of ±2-fold from 6.6-15.1 hrs. Concomitant use of Notolac and probenecid is contraindicated.)

Lithium: Inhibition of renal lithium clearance leading to an increase in plasma lithium concentration.

Methotrexate: Methotrexate clearance is decreased, enhancing the toxicity of methotrexate. The effect of methotrexate on Notolac clearance has not been studied.

Nondepolarizing Muscle Relaxants: Concomitant use of Notolac and muscle relaxants has not been studied so it must be used with caution.

ACE Inhibitors: Renal impairment will be increased especially in volume-depleted patients.

Antiepileptic Drugs (Phenytoin, Carbamazepine): Convulsion attacks occurred (sporadic cases).

Psychoactive drugs (Fluoxetine, Tiotixene, Alprazolam): Hallucinations.

Morphine: No detrimental interactions are observed. Do not mix Notolac and morphine in the same syringe.

There are no reports of interactions between Notolac and antibacterials, antiemetics, laxatives, sedative, anxiolytics, corticosteroids, bronchodilators or hormones.

No evidence (in animal or human studies) shows that Notolac induces or inhibits hepatic enzymes capable of metabolizing itself or other drugs.

See also:
What are the possible side effects of Notolac?

Adverse reaction rates increase with higher doses of Notolac (Notolac tromethamine). Practitioners should be alert for the severe complications of treatment with Notolac (Notolac tromethamine), such as GI ulceration, bleeding and perforation, postoperative bleeding, acute renal failure, anaphylactic and anaphylactoid reactions and liver failure. These NSAID-related complications can be serious in certain patients for whom Notolac (Notolac tromethamine) is indicated, especially when the drug is used inappropriately.

In patients taking Notolac (Notolac tromethamine) or other NSAIDs in clinical trials, the most frequently reported adverse experiences in approximately 1% to 10% of patients are:

Additional adverse experiences reported occasionally ( < 1% in patients taking Notolac (Notolac tromethamine) or other NSAIDs in clinical trials) include:

Body as a Whole: fever, infections, sepsis

Cardiovascular: congestive heart failure, palpitation, pallor, tachycardia, syncope

Dermatologic: alopecia, photosensitivity, urticaria

Gastrointestinal: anorexia, dry mouth, eructation, esophagitis, excessive thirst, gastritis, glossitis, hematemesis, hepatitis, increased appetite, jaundice, melena, rectal bleeding

Hemic and Lymphatic: ecchymosis, eosinophilia, epistaxis, leukopenia, thrombocytopenia

Metabolic and Nutritional: weight change

Nervous System: abnormal dreams, abnormal thinking, anxiety, asthenia, confusion, depression, euphoria, extrapyramidal symptoms, hallucinations, hyperkinesis, inability to concentrate, insomnia, nervousness, paresthesia, somnolence, stupor, tremors, vertigo, malaise

Reproductive, female: infertility

Respiratory: asthma, cough, dyspnea, pulmonary edema, rhinitis

Special Senses: abnormal taste, abnormal vision, blurred vision, hearing loss

Urogenital: cystitis, dysuria, hematuria, increased urinary frequency, interstitial nephritis, oliguria/polyuria, proteinuria, renal failure, urinary retention

Other rarely observed reactions (reported from postmarketing experience in patients taking Notolac (Notolac tromethamine) or other NSAIDs) are:

Body as a Whole: angioedema, death, hypersensitivity reactions such as anaphylaxis, anaphylactoid reaction, laryngeal edema, tongue edema, myalgia

Cardiovascular: arrhythmia, bradycardia, chest pain, flushing, hypotension, myocardial infarction, vasculitis

Dermatologic: exfoliative dermatitis, erythema multiforme, Lyell's syndrome, bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis

Gastrointestinal: acute pancreatitis, liver failure, ulcerative stomatitis, exacerbation of inflammatory bowel disease (ulcerative colitis, Crohn's disease)

Hemic and Lymphatic: agranulocytosis, aplastic anemia, hemolytic anemia, lymphadenopathy, pancytopenia, postoperative wound hemorrhage (rarely requiring blood transfusion - see BOXED WARNING, WARNINGS, and PRECAUTIONS)

Metabolic and Nutritional: hyperglycemia, hyperkalemia, hyponatremia

Nervous System: aseptic meningitis, convulsions, coma, psychosis

Respiratory: bronchospasm, respiratory depression, pneumonia

Special Senses: conjunctivitis

Urogenital: flank pain with or without hematuria and/or azotemia, hemolytic uremic syndrome

Postmarketing Surveillance Study

A large postmarketing observational, nonrandomized study, involving approximately 10,000 patients receiving Notolac tromethamineA.