Sprix (Ketorolac Nasal Spray) is a non-steroidal anti-inflammatory drug that is used to treat moderately severe pain. It provides pain relief like opioid analgesics. Ketorolac nasal spray should be used only for short-term relief of pain (treatment should not exceed five days). Also Read: Ketorolac (Toradol) Injection and Tablets

Sprix (Ketorolac Nasal Spray) Uses:

• Moderate to moderately severe Pain:

  • It is indicated for the management of  moderate or severe pain for short term duration i.e up to 5 days in adults that requires opioid level analgesia

• Off Label Use of Ketorolac in Adults:

  • Migraine

Sprix (Ketorolac Nasal Spray) Dose in Adults:

Sprix (Ketorolac Nasal Spray) Dose in the treatment of moderate to moderately severe pain:

Note: The maximum combined duration of treatment is 5 days for both nasal spray or other formulations of ketorolac. Intranasal:

• Adults <65 years and ≥50 kg:

  • One spray (15.75 mg) in each nostril (total dose: 31.5 mg) given every 6 - 8 hourly
  • Maximum dose: 4 doses : 126 mg/day.
• Dosage adjustments in adults with low body weight (<50 kg):
  • One spray (15.75 mg) in only 1 nostril (total dose: 15.75 mg) given every 6 to 8
  • Maximum dose: 4 doses: 63 mg/day.

Sprix (Ketorolac Nasal Spray) Dose in the treatment of Migraine, acute abortive treatment (off-label):

• Intranasal: One spray (15.75 mg) in each nostril (total dose: 31.5 mg)
• Given as a single dose

Use in Children:

Not indicated.

Pregnancy Risk Factor C (D ≥30 weeks gestation)

• Contraindicated during labor or delivery
• Animal reproduction studies show no adverse effects
• Avoid starting ketorolac before 30 weeks gestation. NSAIDs can cause premature closure of the ductus Arteriosus.

Ketorolac use during breastfeeding:

• After oral administration, Ketorolac excretes from breast milk.
• According to the manufacturer, a decision to give ketorolac to a lactating mom should be made after considering the risks to infant exposure, the benefits to breastfeeding and the benefits to the mother.

Sprix (Ketorolac Nasal Spray) Dose in Kidney Disease:

• Renal insufficiency:
  • Intranasal: One spray (15.75 mg) in 1 nostril (total dose: 15.75 mg) given every 6 - 8 hourly
  • Maximum dose: 4 doses: 63 mg/day
• Advanced renal impairment (or at risk for renal failure due to volume depletion):
  • Contraindicated

Sprix (Ketorolac Nasal Spray) Dose in Liver disease:

• Caution advised for patients with hepatic impairment or history of hepatic disease
• it may cause elevation of liver enzymes
• If clinical signs and symptoms of liver disease develop, discontinue the drug.

• Events reported with intranasal use; refer to Ketorolac (Systemic) monograph for other potential ketorolac-related adverse events.

Common Side Effects of Sprix (Ketorolac Nasal Spray):

• Respiratory:

  • Nasal discomfort
  • Sore nose

Less Common Side Effects of Sprix (Ketorolac Nasal Spray):

• Cardiovascular:

  • Bradycardia
  • Hypertension

• Dermatologic:

  • Skin Rash

• Genitourinary:

  • Oliguria
  • Decreased Urine Output

• Hepatic:

  • Increased Serum ALT
  • Increased Serum AST

• Ophthalmic:

  • Increased Lacrimation

• Respiratory:

  • Throat Irritation
  • Rhinitis

Contraindications to Sprix (Ketorolac Nasal Spray):

• Hypersensitivity to any ingredient of the ketorolac formulation
• Active acid peptic illness
• Recent gastrointestinal bleeding, or perforation
• Due to volume depletion, advanced kidney disease or risk of kidney failure
• History of asthma, urticaria or other allergic-type reactions following aspirin use or any other NSAIDs
• Analgesia prophylactic before major surgery
• Surgery to place coronary artery bypass (CABG),
• Delivery and labor
• Hemostasis critical for those with hemostasis essential, hemorhagic diathesis or suspected cerebrovascular bleeding
• Use pentoxifylline or probenecid in conjunction

Warnings and precautions

• Bleeding

  • It blocks platelet function.
  • Patients with suspected or confirmed cerebrovascular bleeding, hemorhagic diathesis and incomplete hemostasis are contraindicated
  • It causes platelet adhesion to be impaired and aggregation to increase bleeding time.
  • Anemia can be caused by long-term NSAID usage.
  • Rarely, NSAIDs can cause severe blood dyscrasias (eg agranulocytosis or thrombocytopenia and aplasticanemia).

• Cardiovascular events: [US Boxed Warn]

  • There is an increased chance of severe (and possibly fatal) adverse cardiovascular thrombotic reactions, including stroke and MI, due to NSAID use.
  • This risk can occur during treatment, and it may increase as the use continues.
  • Exacerbation or new-onset hypertension can occur. NSAIDs could also affect the response to ACE inhibitors or thiazide diuretics or loop diuretics.
  • May be associated with cardiovascular events
  • BP should always be monitored.
  • Hypertensive patients should be cautious.
  • Patients with edema may experience sodium and fluid retention.
  • Patients with heart failure should be avoided
  • Patients with MI should not be treated unless the benefits are greater than the risk of developing cardiovascular thrombotic complications.
  • To reduce cardiovascular events, the lowest effective dose should only be used for the short time. Patients at high risk should consider alternative therapies.

• Gastrointestinal events [US Boxed Warning]

  • NSAIDs can increase the risk for serious gastrointestinal inflammation, bleeding, ulceration, and perforation (may even be fatal).
  • Patients with a history or peptic ulcer disease, and/or gastrointestinal bleeding are at greater risk of serious GI events.
  • These events can occur without warning and at any time during therapy.
  • Patients with active GI bleeding should be avoided
  • Patients who are taking concurrent therapies that increase the risk of GI bleeding, such as anticoagulants and/or steroids, selective serotonin reuptake inhibiters, smoking, alcohol use, and elderly patients should not be allowed to smoke.
  • You should consider alternative therapies for patients at high-risk.
  • The lowest effective dose should not be used for longer periods of time.
  • Combining ketorolac and aspirin can lead to a significant increase in the likelihood of GI complications, e.g. Ulcer. 
  • Use of gastroprotective therapy, e.g. Proton pump inhibitors are recommended.

• Hepatic effects

  • Rare but sometimes fatal hepatic reactions have been linked to NSAIDs.
  • If the patient has signs or symptoms that indicate liver disease or persisting or worsening abnormal hepatic functions, discontinue treatment
  • If the patient has any systemic manifestations, e.g. Eosinophilia or a rash.

• Hyperkalemia:

  • NSAIDs can increase hyperkalemia risk, especially in elderly people, diabetics, and those who use concomitantly with other agents that may cause hyperkalemia e.g. ACE inhibitors.
  • Pay attention to potassium.

• Hypersensitivity

  • Even patients who have never been exposed to the substance before may be at risk of developing hypersensitivity.
  • Hypersensitivity, including bronchospasm, and anaphylactic shock, may occur. Patients with "aspirin triad" (bronchial asthma. Aspirin intolerance. Rhinitis.
  • Patients who have had a history of rhinitis or NSAID therapy such as bronchospasm or asthma should not be used.
  • Ketorolac nasal spray is contraindicated in patients with prior hypersensitivity reactions to aspirin or NSAIDs.

• Effects on the renal system:

  • With ketorolac, there have been reports of ARF, interstitial Nephritis and nephrotic Syndrome.
  • NSAIDs have been linked to renal injury and papillary necrosis.

• Reactions to skin:

  • Negative effects of NSAIDs on the skin can be severe and potentially life-threatening.
    • exfoliative dermatitis
    • Stevens-Johnson syndrome (SJS)
    • Toxic epidermal Necrolysis (TEN).
  • If you notice any signs of skin rash, hypersensitivity or other symptoms, discontinue use.

• Asthma

  • Patients with asthma that is aspirin-sensitive should not be given this medication. Bronchospasm can become severe and even fatal.
  • Patients with other forms of asthma should be cautious.

• Coronary artery bypass surgery/major surgery: [US-Boxed Warning]

  • Contraindicated for the placement of coronary bypass graft surgery (CABG).
  • After CABG surgery, there is an increased risk of stroke and MI.
  • Not recommended as a prophylactic analgesic prior to major surgery.
  • Ketorolac has been shown to reduce postoperative bleeding and hematomas in perioperative care

• Hepatic impairment

  • Caution is advised in the event of hepatic impairment and a history liver disease.
  • Patients with LFT abnormalities should be closely monitored.

• Hypertension:

  • Use caution as hypertension may develop or worsen existing hypertension.

• Renal impairment

  • It is not recommended for patients with advanced renal impairment or at high risk of renal failure because of volume depletion.
  • NSAIDs can cause kidney dysfunction.
  • Risk factors for renal toxicities:
    • Patients with impaired renal function are more at risk
    • Dehydration
    • hypovolemia,
    • heart failure,
    • liver dysfunction,
    • Seniors who are taking diuretics and ACE inhibitors.
  • To avoid dangerous complications from renal derangement, it is important to hydrate the patient before you start therapy
  • Pay attention to your renal function.
  • Modifying the dose may be necessary in cases of moderate serum creatinine elevation

Monitoring parameters:

• Monitor for weight gain/edema
• renal function (serum creatinine, BUN, urine output)
• Observe for bleeding, bruising
• Look for gastrointestinal effects e.g. abdominal pain, bleeding, and dyspepsia.
• CBC and platelets
• Liver function tests

How to administer Sprix (Ketorolac Nasal Spray)?

Intranasal:

• Do not inhale ketorolac nasal spray
• Each nasal spray bottle contains medication for 1 day of therapy
• Prime by holding the bottle upright and pressing the pump 5 times, before the first use of the nasal spray.
• If the same bottle is used for the rest of the day/doses, no need to prime again.
• Each new nasal spray bottle should be primed before use.
• Blow nose to clear nostrils before using the nasal spray.

Method to use

• Position: Sit up straight or stand; tilt head slightly forward
• Insert the tip of the container into the nostril, keeping the bottle upright, and point bottle toward the back and away from the center of the nose
• Hold breath and spray once, pressing down evenly on both sides of the container.
• Immediately after administration, resume breathing through the mouth to expel the product
• pinch nose to help retain spray if dripping begins
• Repeat in the opposite nostril if 2 sprays are prescribed per dose.

Discard bottle within 24 hours of priming even if there is unused medication.

Mechanism of action of Sprix (Ketorolac Nasal Spray):

• Ketorolac inhibits COX-1 and 2 enzymes reversibly.
• This results in decreased protaglandin precursor production. It has antipyretic and analgesic effects.
• Other proposed methods include inhibiting chemotaxis, altering lymphocyte activity, inhibiting neutrophil aggregation/activation, and decreasing pro-inflammatory cytokine levels are not fully explained and accepted.

Onset of analgesia:

• Within 20 minutes

Absorption:

• Rapid and well absorbed.

Distribution:

• ~13 L following complete distribution
• ketorolac is deposited mainly in the nasal cavity and pharynx;
• In esophagus  and <20% and  <0.5% in the lungs

Protein binding:

• 99%

Metabolism:

• Hepatic to hydroxylated and conjugated forms

Bioavailability:

• ~60% relative to intramuscular administration

Half-life elimination:

• ~5 to 6 hours (similar to IM administration)

Time to peak:

• 0.75 hours

Excretion:

• Urine (~92%, ~60% as unchanged drug)
• feces ~6%

International Brand Names of Ketorolac Nasal Spray:

• Sprix
• Aspriks

Ketorolac Nasal Spray Brand Names in Pakistan:

No Brands Available in Pakistan.