Package leaflet: Information for the patient

NASVICAL 30 mg/ml solution for injection

Ketorolac tromethamine
Equivalent medicine
Please read this leaflet carefully before this medicine is administered to you because
it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it could be harmful.
If you experience any adverse reaction, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet

What Nasvical is and what it is used for
What you need to know before being administered Nasvical
How Nasvical is administered
Possible side effects
How to store Nasvical
Contents of the pack and other information

1. What Nasvical is and what it is used for

Nasvical contains ketorolac tromethamine. It belongs to a group of medicines called
"non-steroidal anti-inflammatory/anti-rheumatic drugs (NSAIDs)" which have several actions, including
an important role in pain control.
Nasvical is used:

for the short-term treatment (maximum 2 days) of moderate to severe acute pain following surgery (postoperative pain), administered into a muscle (intramuscularly) or through a vein (intravenously);
as an adjunct to opioid-based pain therapy in cases of major surgery or very intense pain, administered intravenously;
in the treatment of pain due to renal colic.

2. What you should know before taking Nasvical

Do not take Nasvical:

if you are allergic to ketorolac tromethamine or to any of the other ingredients of this medicine (listed in section 6);
if you have mild or ongoing (chronic) pain;
if you are allergic to other NSAIDs;
if you have had severe and sudden allergic reactions (anaphylactic reactions) to aspirin (acetylsalicylic acid) or to other medicines in the same class (prostaglandin synthesis inhibitors);
if you have nasal polyps (complete or partial nasal polyposis syndrome);
if you have swelling of the legs, arms, face, mouth, or tongue (angioedema);
if you experience difficulty breathing (bronchospasm, asthma);
if you have a history of bleeding, perforation, or injury, or have pain and burning in the stomach or intestines (active peptic ulcer);
if you have serious heart problems (severe heart failure);
if you have or have had bleeding in the brain or even a suspected brain bleed (cerebrovascular hemorrhage);
if you have reduced blood volume (hypovolemia) or lack of body water (dehydration);
if you have moderate or severe kidney problems (moderate or severe renal impairment - serum creatinine below 1.8 mg/dl);
if you have severe liver damage or inflammation (liver cirrhosis or severe hepatitis);
if you have a tendency to bleed easily (hemorrhagic diathesis, coagulation disorders);
if you are being treated with blood-thinning medicines (anticoagulants);
if you are currently taking aspirin (acetylsalicylic acid), other NSAIDs, lithium salts (for mental health conditions), probenecid (for gout treatment), or pentoxifylline (to improve blood circulation) (see "Other medicines and Nasvical");
if you are being treated with medicines that greatly increase urine production (diuretics);
if you are trying to prevent pain (analgesia) before or during surgery;
if you have undergone surgery with a high risk of bleeding (hemorrhage or incomplete hemostasis);
if you are a child or adolescent under 16 years of age;
if you are in the last three months of pregnancy (third trimester), in labor, giving birth, or breastfeeding (see "Pregnancy, breastfeeding and fertility");
if a specific route of administration is required (neuraxial use: epidural or intrathecal).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before being given Nasvical:

if you have or have had stomach or intestinal diseases, as the risk of toxicity is high, especially if you use Nasvical outside the approved indications and/or for prolonged periods (see also "What Nasvical is and what it is used for", "Do not use Nasvical", and "How to take Nasvical");
if you are taking other anti-inflammatory medicines (see "Other medicines and Nasvical");
if you are elderly or very weak, as you may be more likely to experience certain adverse effects from Nasvical such as stomach or intestinal bleeding and perforation;
if you have chronic inflammatory bowel diseases (ulcerative colitis and Crohn's disease);
if you are taking anti-inflammatory hormones (oral corticosteroids), blood-thinning medicines (anticoagulants such as warfarin), antidepressants (selective serotonin reuptake inhibitors), or medicines such as aspirin or similar agents (see "Other medicines and Nasvical");
if you have experienced significant allergic reactions (anaphylactic reactions, bronchospasm, skin redness, rashes, low blood pressure, throat swelling, or swelling of the legs, arms, face, mouth, or tongue), which may occur in patients with or without a history of allergy to Nasvical, other NSAIDs, or aspirin;
if you have a history of swelling in the legs, arms, face, mouth, or tongue (angioedema), breathing difficulties (bronchospasm, asthma), or nasal polyps;
if you have high blood pressure and/or your heart does not pump enough blood (mild to moderate congestive heart failure);
if you have blood vessel problems affecting the heart (chronic ischemic heart disease), legs (peripheral arterial disease), or brain (cerebrovascular disease);
if you have high levels of fat in the blood (hyperlipidemia);
if you have diabetes;
if you smoke;
if you have kidney problems;
if you have liver problems;
if you have bleeding disorders;
if you have skin reactions (exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, skin rash, mucosal lesions) or any other signs of allergy;
if you are planning a pregnancy;
if you have fertility problems or are undergoing fertility investigations.

Inform your doctor if you have recently undergone or are about to undergo surgery on the stomach or intestinal tract before receiving/using Nasvical, as Nasvical may sometimes impair wound healing in the intestine after surgery.
Nasvical does not cause dependence. Withdrawal symptoms have not been observed after abrupt discontinuation of treatment.
Although Nasvical has not been shown to increase the risk of events such as heart attack, this risk cannot be ruled out.
Warning: Nasvical cannot be considered a simple painkiller and must be used under strict medical supervision.
Do not use Nasvical for the treatment of mild or chronic pain.
Children and adolescents
Nasvical is contraindicated in children and adolescents under 16 years of age.
Other medicines and Nasvical
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Concurrent use of Nasvical with the following should be avoided:

non-steroidal anti-inflammatory drugs (NSAIDs) and medicines of the same class as aspirin (ASA), as they increase the risk of serious adverse effects;
corticosteroids (hormones used against inflammation), as they increase the risk of serious stomach and intestinal injuries and bleeding (see "Warnings and precautions");
anticoagulants (medicines that thin the blood), as Nasvical may enhance the effects of anticoagulants such as warfarin, heparin, and dextrans;
antiplatelet agents (aspirin or similar medicines) and selective serotonin reuptake inhibitors (medicines for depression), as they may increase the risk of stomach and intestinal bleeding and prolong bleeding time;
pentoxifylline (a medicine to improve blood circulation), as it increases the tendency to bleed;
probenecid (a medicine for gout), as it increases the amount and duration of Nasvical in the body;
methotrexate (a medicine for cancer, arthritis, and immune system disorders), as it may remain in the body longer, increasing the risk of toxicity;
lithium (a medicine for mental health conditions), as its blood levels may increase when taken together with Nasvical;
diuretics, ACE inhibitors, and angiotensin II receptor antagonists (medicines to lower blood pressure), as their effect may be reduced when taken with Nasvical and the risk of kidney damage may increase in some dehydrated or elderly patients who already have impaired kidney function;
furosemide (a medicine to increase urine output), as its effect may be reduced.

Nasvical reduces the need for opioid-derived medicines to control pain after surgery.
Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before being given this medicine.
Do not take NASVICAL during the last 3 months of pregnancy, as it may harm the unborn baby or cause problems during delivery. It may cause kidney and heart problems in the unborn child. It may affect your bleeding tendency and that of your baby, and may delay or prolong labor.
You should not take NASVICAL during the first 6 months of pregnancy unless absolutely necessary and advised by your doctor. If treatment is needed during this period or when trying to conceive, the lowest possible dose for the shortest possible time should be used. If taken for more than a few days starting from the 20th week of pregnancy, NASVICAL may cause kidney problems in the fetus that can reduce the levels of amniotic fluid surrounding the baby (oligohydramnios) or cause narrowing of a blood vessel (ductus arteriosus) in the baby's heart. If treatment is needed for more than a few days, your doctor may recommend additional monitoring.
The use of Nasvical is contraindicated during the last 3 months of pregnancy (third trimester), during labor, and delivery.
Do not use Nasvical during the first and second trimesters of pregnancy unless strictly necessary.
If you are trying to conceive or are in the first or second trimester of pregnancy, the dose and duration of treatment with Nasvical should be kept as low as possible.
If you are of childbearing age, you should avoid any possible pregnancy before starting treatment and use an effective contraceptive method during treatment.
Breastfeeding
This medicine passes into breast milk. Do not use Nasvical while breastfeeding.
Fertility
The use of Nasvical may reduce fertility and is not recommended if you are planning a pregnancy. If you have difficulty conceiving or are undergoing fertility tests, you should consider stopping Nasvical.
Driving and using machines
You may experience drowsiness, dizziness, vertigo, sleep disturbances (insomnia), or mood changes (depression) while using Nasvical. If you experience these or similar side effects, avoid activities requiring alertness.
Therefore, caution is advised when driving or operating machinery.
Nasvical contains ethanol
This medicine contains 100 mg of alcohol (ethanol) per milliliter, equivalent to 10% w/v. The alcohol content in a 1 ml vial of this medicine is equivalent to 2.5 ml of beer and 1 ml of wine. The small amount of alcohol in this medicine will not produce significant effects.
Nasvical contains less than 1 mmol (23 mg) of sodium per vial, i.e., essentially "sodium-free".

3. How to use Nasvical

Use this medicine exactly as directed by your doctor. If you have any doubts, consult your
doctor or pharmacist.
This medicine will be administered by a doctor or healthcare professional. Your doctor will
prescribe the lowest effective dose according to the severity of your pain and your response to
treatment.
The duration of treatment must not exceed 2 days in case of rapid administration (bolus) and 1
day in case of slow administration (continuous infusion).
Intramuscular administration (into the muscle)
Adults
The recommended initial dose is 10 mg, followed by doses of 10–30 mg repeated every 4–6 hours as
needed, up to a maximum of 90 mg per day, using the lowest effective dose.
The duration of treatment must not exceed 2 days.
Your doctor will advise you on how to switch from injectable therapy to oral therapy with Nasvical (the total daily dose must not be exceeded, remembering that the maximum oral dose must not exceed 40 mg).
The dose will be appropriately reduced by the doctor in patients weighing less than 50 kg.
Intravenous administration (into the vein)
Intravenous use of this preparation is restricted to hospitals and clinics.
Adults
For severe acute pain, the recommended initial dose is 10 mg, followed by doses of 10–30 mg repeated every 4–6 hours as needed, using the lowest effective dose. If necessary, treatment may continue at longer intervals, but the total daily dose must not exceed 90 mg.
Renal colic
If you suffer from renal colic, the recommended dose is one 30 mg vial administered intramuscularly or intravenously.
Elderly (aged 65 years or older)
The maximum daily dose must not exceed 60 mg per day.
Use in children and adolescents
The use of this medicine is contraindicated in individuals under 16 years of age.
If you use more Nasvical than you should
If you take too much Nasvical, contact your doctor immediately or go to the nearest hospital.
Some symptoms of overdose may include abdominal pain, nausea, vomiting, rapid breathing (hyperventilation), damage to the stomach or intestinal lining and/or inflammation which may be accompanied by bleeding (peptic ulcer and/or erosive gastritis, gastrointestinal bleeding), kidney dysfunction, severe and rapid generalized allergic reactions (anaphylactoid reactions). Rarely, increased blood pressure, kidney problems (acute renal failure), breathing difficulties (respiratory depression), and coma may occur.
Treatment: There are no specific antidotes. Symptomatic and supportive treatment should be administered, together with standard safety measures (induction of vomiting, gastric lavage, administration of activated charcoal).
Dialysis does not significantly remove ketorolac from the bloodstream.
If you forget to use Nasvical
Do not take a double dose to make up for a missed dose.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
The following side effects may occur with Nasvical:

Frequency not known (frequency cannot be estimated from the available data)

inflammation of the membranes surrounding the brain (aseptic meningitis)
decrease in a type of blood cells (thrombocytopenia)
red spots on the body (purpura)
nosebleeds
severe and rapid generalized allergic reactions (anaphylaxis, anaphylactoid reactions)
allergic reactions such as bronchial constriction causing breathing difficulties (bronchospasm)
dilation of blood vessels
hot flushes
skin rash
throat swelling (laryngeal edema)
loss of appetite
increased potassium levels and decreased sodium levels in the blood
abnormal thinking
mood disorders (depression)
sleep disturbances (insomnia)
anxiety, irritability, nervousness
severe disturbances in mental balance (psychotic reactions)
abnormal dreams
hallucinations
euphoria
reduced ability to concentrate
decreased sensitivity and reduced reflex responsiveness (stupor)
confusion
headache
dizziness
seizures
altered skin sensation, tingling (paresthesia)
excessive movement (hyperkinesia)
taste disturbances
vision disorders, altered vision
ringing in the ears (tinnitus), hearing loss
vertigo
irregular or rapid heartbeat (palpitations)
reduced heart rate (bradycardia), reduced heart function (heart failure)
swelling (edema)
increased or decreased blood pressure
heart problems (cardiac failure)
bruising (hematomas)
redness
paleness
bleeding from surgical wound
heart attack
damage to blood vessels in the brain (stroke)
fluid accumulation in the lungs (pulmonary edema)
breathing difficulties (dyspnea, asthma)
injury to the stomach or intestinal wall, which may perforate and be accompanied by bleeding (peptic ulcer, ulcer, gastrointestinal perforation or hemorrhage)
nausea
vomiting
diarrhea
passage of gas from the anus (flatulence)
constipation
stomach pain/discomfort (dyspepsia), abdominal pain/discomfort, feeling of fullness
blood in the stool (melena) and from the lower end of the intestine (rectal bleeding)
vomiting blood
inflammation of the mouth (stomatitis, ulcerative stomatitis) and of the esophagus
belching
inflammation of the pancreas
dry mouth
worsening of inflammation in a part of the intestine called the colon (exacerbation of colitis), or of the stomach (gastritis)
worsening of a chronic inflammatory bowel disease (Crohn's disease)
liver inflammation
yellowing of the skin and eyes (cholestatic jaundice)
impaired liver function (hepatic failure)
rapid swelling of legs, arms, face, or tongue (angioedema)
skin inflammation with peeling (exfoliative dermatitis)
sweating
skin rash with redness and bumps (maculopapular rash)
hives, itching
blistering reactions including a condition called Stevens-Johnson syndrome with severe skin, mouth, and other body lesions associated with high fever, vomiting, diarrhea, and joint pain
skin death (toxic epidermal necrolysis)
muscle pain
increased urine volume, increased frequency of urination, decreased urine volume
kidney disorders (renal failure, hemolytic-uremic syndrome, interstitial nephritis, urinary retention, nephrotic syndrome, flank pain)
infertility in women
muscle weakness (asthenia)
fever
injection site reactions
chest pain
excessive thirst
prolonged bleeding time and changes in certain blood tests (increased urea, increased creatinine, altered liver function tests).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor or pharmacist.
You may also report side effects directly via the national reporting system at www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Nasvical

Keep this medicine out of the sight and reach of children.
Store this medicine in its original packaging to protect it from light.
Do not use this medicine after the expiry date stated on the carton after "Exp.".
The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Nasvical contains

The active substance is ketorolac tromethamine. One 1 ml vial contains 30 mg of ketorolac tromethamine.
The other components are ethanol, sodium chloride, water for injections.

Description of the appearance of Nasvical and package contents
Nasvical is presented as an injectable solution for intramuscular or intravenous use.
It is available in the following pack:
30 mg/ml injectable solution: 3 vials of 1 ml.
Marketing Authorization Holder
I.B.N. SAVIO S.r.l. – Via del Mare, 36 – 00071 Pomezia (RM)
Manufacturer and final controller
Savio Industrial S.r.l. – Via E. Bazzano, 14 – Ronco Scrivia (GE)

The following information is intended exclusively for physicians or healthcare professionals:
Warning: the injectable solution contains ethanol; therefore, neuroaxial administration (epidural or intrathecal) is contraindicated.
Nasvical is compatible with aminophylline, lidocaine, morphine, meperidine, dopamine, insulin, and heparin when mixed together in a solution contained in an intravenous infusion bag for e.v. administration,
but it must not be mixed with morphine, meperidine, promethazine, or hydroxyzine in the same syringe.
Injections must be performed according to strict standards of sterilization, asepsis, and antisepsis.
The administered dose should be the lowest effective dose according to the severity of pain and the patient's response.