Osteonorm

Package leaflet: Information for the patient

OSTEONORM 200 mg + 40 mg injectable solution with lidocaine

Clodronic acid - Lidocaine
Generic medicine
Read this leaflet carefully before using this medicine 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 their symptoms are the same as yours, because it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What OSTEONORM is and what it is used for
2. What you need to know before using OSTEONORM
3. How to use OSTEONORM
4. Possible side effects
5. How to store OSTEONORM
6. Contents of the pack and other information

1. What OSTEONORM is and what it is used for

OSTEONORM is a medicine containing clodronic acid, which belongs to a group of medicines used to treat bone diseases, called bisphosphonates.
OSTEONORM is used in women for the prevention and treatment of bone thinning (osteoporosis) after menopause (the period of permanent menstrual cessation).

2. What you need to know before using OSTEONORM

Do not use OSTEONORM

• If you are allergic to clodronic acid or to any of the other ingredients of this medicine (listed in section 6).
• If you are taking other bisphosphonates, medicines similar to OSTEONORM.
• If you are allergic to lidocaine or to other amide-type local anesthetics, such as bupivacaine, mepivacaine, ropivacaine, levobupivacaine.
• If you have a heart condition causing loss of consciousness (Adam-Stokes syndrome).
• If you have a heart rhythm disorder (Wolff-Parkinson-White syndrome, atrial fibrillation, sinoatrial, atrioventricular or intraventricular block).
• If you have a weak heart unable to supply adequate blood flow to the body (acute heart failure).
• If you have a condition characterized by reduced blood volume (hypovolemia).

The medicine is intended for intramuscular use only (i.e. injected into a muscle) and must not be administered
into a blood vessel (intravenously). Accidental injection into a vein increases the risk
of serious adverse reactions due to high blood levels of the anesthetic lidocaine (see
section 3. If you use more OSTEONORM than you should).
Warnings and precautions
Talk to your doctor or pharmacist before using OSTEONORM.
Before and during treatment, your doctor will ask you to undergo blood tests to monitor
the function of your kidneys and liver (see section 4. Possible side effects). It is important
that you drink an adequate amount of fluids during treatment with this medicine, especially if you
have liver or kidney problems.
In particular, inform your doctor:

• If you have high levels of calcium in your blood.
• If you have kidney disease (renal insufficiency).
• If you are being treated with OSTEONORM for cancer or to treat osteoporosis, and are undergoing dental treatment or need dental surgery (see section 4. Possible side effects), as you may require preventive dental care.
• If you have heart diseases (particularly heart rhythm disorders with low heart rate and heart failure) or have had heart surgery.
• If you have severe liver disease.
• If you, or someone in your family, suffer from a condition causing a marked increase in body temperature following the use of local anesthetics such as lidocaine (malignant familial hyperthermia).
• If you experience thigh, hip or groin pain or weakness during treatment, as this may be an early symptom of a possible femoral fracture (see section 4. Possible side effects).
• If you suffer from seizures (epilepsy). Your doctor will closely monitor you for any possible symptoms.
• If you have respiratory or pulmonary disorders.
• If you have a disease causing muscle weakness (myasthenia gravis).
• If you have porphyria (a rare inherited blood disorder affecting the skin and nervous system).

Children and adolescents
The safety and efficacy of this medicine in pediatric patients have not been established.
Other medicines and OSTEONORM
Inform your doctor or pharmacist if you are currently using, have recently used, or might use any other
medicine.
This is particularly important if:

• You are taking other bisphosphonates, medicines used to treat bone diseases, as concomitant use of OSTEONORM with other bisphosphonates is contraindicated (see section 2. Do not use OSTEONORM).
• You are taking non-steroidal anti-inflammatory drugs (NSAIDs), medicines used to treat inflammation (particularly diclofenac), as kidney problems may occur.
• You are taking aminoglycosides, medicines used to treat infections, as calcium levels in the blood may decrease (hypocalcemia).
• You are taking estramustine, a medicine used to treat prostate cancer (a gland in men that produces seminal fluid), as blood levels of estramustine may increase.
• You are taking medicines used to treat heart disorders, including irregular heartbeat, such as beta-blockers (e.g. propranolol), calcium channel blockers (e.g. amiodarone) or sodium channel blockers, as lidocaine may remain in the bloodstream longer.
• You are taking cimetidine, a medicine mainly used to treat gastritis and gastric ulcer (a lesion of the stomach wall); fluvoxamine (a medicine used for depression); antiviral medicines such as ritonavir; macrolide antibiotics such as erythromycin or antibiotics like ciprofloxacin; antifungal medicines such as ketoconazole, itraconazole, as this may lead to increased blood levels of lidocaine.
• You are taking barbiturates such as phenobarbital; medicines used to treat epilepsy such as carbamazepine; phenytoin; primidone; oral contraceptives or hormone replacement therapy, as this may lead to decreased blood levels of lidocaine.
• You are being treated with digitalis, medicines used to treat heart rhythm disorders, as this may increase the risk of heart rhythm disturbances.
• You are taking medicines used to relax muscles during general anesthesia, such as suxamethonium.
• The solution is incompatible with alkaline solutions or oxidizing solutions.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding,
please consult your doctor or pharmacist before using this medicine.
Pregnancy
Avoid using OSTEONORM during pregnancy or if you are of childbearing age and not using an effective
contraceptive method (medicines used to prevent pregnancy).
Breastfeeding
It is not known whether clodronic acid passes into breast milk, whereas lidocaine is excreted in breast milk in
small amounts. Therefore, during treatment with OSTEONORM, breastfeeding should be discontinued.
Fertility
It is not known whether clodronic acid and lidocaine have effects on human fertility.
Driving and using machines
OSTEONORM may cause visual disturbances that could affect your ability to drive or
operate machinery.
If you experience one or more of the symptoms listed in section 4 or if you use more OSTEONORM than you should, avoid driving and operating machinery.
Important information about certain excipients
OSTEONORM contains sodium
OSTEONORM 200 mg + 40 mg injectable solution with lidocaine contains 32.9 mg of sodium (the main
component of table salt) per dose, equivalent to 1.6% of the maximum daily recommended dietary intake
for an adult.

3. How to use OSTEONORM

Use this medicine exactly as your doctor has instructed you. Your doctor will determine the correct dose according to the severity of your condition and the duration of treatment. If you have any doubts, consult your doctor or pharmacist (see the section DOSAGE, METHOD AND DURATION OF ADMINISTRATION at the end of this Package Leaflet).
Clodronic acid is primarily eliminated via the kidneys. Therefore, adequate fluid intake must be maintained during treatment with clodronic acid.
Method of administration
OSTEONORM 200 mg + 40 mg solution for injection with lidocaine is for intramuscular use only (i.e. to be injected into a muscle). To avoid accidental injection into a blood vessel, it is recommended to aspirate before injecting the medicine.
Do not massage the injection site.
If you use more OSTEONORM than you should
If you accidentally take too much OSTEONORM, contact your doctor or go to the nearest hospital immediately.
Symptoms of overdose may include:

• increased blood creatinine levels and kidney disease (renal dysfunction) (with high doses of clodronic acid administered intravenously),
• elevated blood nitrogen levels (uraemia),
• liver damage,
• low levels of calcium in the blood (hypocalcaemia).

In case of accidental intravascular injection, the following symptoms of lidocaine overdose may occur:

• drowsiness,
• drunkenness (state of excessive excitement),
• sedation (physical and mental relaxation),
• loss of sensation in certain parts of the body (paraesthesia),
• muscle spasms (sudden involuntary muscle contractions), uncontrolled body movements (convulsions),
• reduced blood flow to the body (cardiovascular collapse).

Treatment
The doctor will monitor symptoms and provide specific treatments.
If you forget to use OSTEONORM
Do not use a double dose to make up for the forgotten dose.
If you stop treatment with OSTEONORM
If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you experience any eye or vision disturbances during treatment, STOP the treatment and consult an ophthalmologist.
Inform your doctor immediately if you experience:

• pain or sores in the mouth or jaw and/or maxilla (two facial bones), as these may be early signs of serious problems (bone tissue death in the jaw and/or maxilla), generally associated with tooth extraction and/or local infection (see section 2. Warnings and precautions).

The possible side effects are listed below by frequency:
Common (may affect up to 1 in 10 people)

• decreased levels of calcium in the blood, without symptoms (asymptomatic hypocalcemia),
• diarrhoea, nausea, vomiting (usually mild in intensity),
• increased levels of transaminases in the blood (a test to assess liver function), usually within normal ranges.

Rare (may affect up to 1 in 1,000 people)

• decreased levels of calcium in the blood, with symptoms (symptomatic hypocalcemia),
• increased levels of parathyroid hormone (a hormone regulating blood calcium levels) associated with low blood calcium,
• increased levels of alkaline phosphatase in the blood (a test to assess bone and liver condition),
• increased levels of transaminases in the blood (a test to assess liver function) more than twice the upper normal limit, without other liver function abnormalities,
• allergic reactions manifesting as skin reactions,
• unusual fracture of the femur (long bone of the leg), particularly in patients receiving long-term treatment for osteoporosis. Contact your doctor if you experience pain or weakness in the thigh, hip, or groin, as this may be an early sign of a possible femoral fracture.

Very rare (may affect up to 1 in 10,000 people)

• Consult your doctor if you experience ear pain, ear discharge, and/or ear infection. These events could be signs of bone damage in the ear.

The following side effects may also occur, for which frequency cannot be estimated from the available data:

• Effects related to the eyes

  • inflammation of the conjunctiva, the membrane covering the eye and inner eyelids (conjunctivitis)
  • eye inflammation (episcleritis, scleritis, and uveitis). Episcleritis and scleritis have been reported with other drugs in the same class as clodronic acid (bisphosphonates)

• Effects related to the lungs

  • breathing difficulties in patients with asthma sensitive to acetylsalicylic acid (a medicine used to treat fever, pain, and inflammation)
  • allergic reactions manifesting as respiratory problems

• Effects related to the kidneys and urinary tract

  • kidney disease (renal failure), severe kidney damage. Rarely, and especially in association with NSAIDs (medicines used to treat inflammation and pain), renal failure has led to death (more frequently with concomitant use of diclofenac). See section 2. Other medicines and Osteonorm.

• Effects related to bones and muscles

  • severe bone, joint, and muscle pain. The onset of symptoms varies from days to several months after starting treatment with OSTEONORM.
  • pain or sores in the mouth or jaw and/or maxilla (two facial bones). These may be early signs of serious problems (bone tissue death in the jaw and/or maxilla), generally associated with tooth extraction and/or local infection (see section 2. Warnings and precautions). In most cases, this occurred in cancer patients.

• Effects related to the injection site

  • pain at the injection site, particularly considering the duration of treatment.

Side effects specific to lidocaine
The following side effects are associated with lidocaine; however, insufficient data are available to determine the frequency of the individual effects listed. Side effects are generally due to either allergic reactions or excessively high blood concentrations resulting from accidental intravascular injection and/or overdose. This may occasionally cause central nervous system excitation and occasional cardiovascular depression (see section 2. Warnings and precautions).

Immune system disorders
Severe allergic reaction (anaphylactoid), swelling of the larynx leading to breathing difficulty (bronchospasm), and drop in blood pressure (cardiorespiratory collapse) due to anaphylactic shock.

Nervous system disorders
Manifestations of excitation or depression associated with dizziness, drowsiness, visual disturbances, tremors, followed by changes in consciousness, seizures, coma, prolonged contraction of the jaw muscles leading to tight closure of the jaw and maxilla (trismus), altered sensation in limbs or other body parts (paraesthesia).

Psychiatric disorders
Anxiety, disorientation.

Cardiac disorders
Slowing of the heartbeat (bradycardia), changes in heart rhythm (arrhythmias), myocardial depression up to cardiac arrest.

Eye disorders
Pupil dilation (mydriasis), blurred vision, double vision (diplopia).

Gastrointestinal disorders
Nausea, vomiting.

Respiratory, thoracic and mediastinal disorders
Difficulty breathing (dyspnoea), reduced respiratory rate (respiratory depression).

Vascular disorders
Low blood pressure (hypotension), high blood pressure (hypertension), interruption of normal blood circulation due to cardiac arrest and reduced blood flow (circulatory collapse).

Skin and subcutaneous tissue disorders
Sudden reddening of the skin (various types of skin rashes), skin rash with more or less itchy wheals (urticaria), itching.

Ear and labyrinth disorders
Ringing in the ears (tinnitus), increased sensitivity to relatively weak sounds (hyperacusis).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at the following website: https://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 OSTEONORM

Keep in the original packaging to protect the medicine from light.
Keep this medicine out of the sight and reach of children.
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 OSTEONORM contains
OSTEONORM 200 mg + 40 mg injectable solution with lidocaine

• The active substances are Clodronic acid, disodium salt (disodium clodronate) 200 mg and Lidocaine hydrochloride 40 mg.
• The other components are Sodium bicarbonate (see section 2. OSTEONORM contains sodium), water for injections.

Description of the appearance of OSTEONORM and contents of the package
OSTEONORM 200 mg + 40 mg injectable solution with lidocaine
Clear, colourless solution.
Injectable solution supplied in packs of 1, 3, 5 or 6 vials for intramuscular use.
Marketing Authorization Holder and Manufacturer
MARKETING AUTHORIZATION HOLDER
I.B.N. Savio S.r.l., Via del Mare, 36 00071 Pomezia (RM)
MANUFACTURER
OSTEONORM 200 mg + 40 mg injectable solution with lidocaine
Savio Industrial S.r.l., Via E. Bazzano n° 14 – Ronco Scrivia (GE)
Biomedica Foscama Industria Chimico-Farmaceutica S.p.A., Via Morolense 87, Ferentino – Italy
The manufacturing site responsible for release of the medicinal product will be indicated in each package leaflet.

The following information is intended exclusively for physicians or healthcare professionals:
DOSAGE, METHOD AND DURATION OF ADMINISTRATION
Prevention and treatment of postmenopausal osteoporosis
The dosage according to clinical condition and bone mineral density values may vary as reported below.
OSTEONORM 200 mg + 40 mg injectable solution with lidocaine
by intramuscular route: 200 mg every 14–28 days for 1 year or longer, depending on the patient's condition.
OSTEONORM 200 mg + 40 mg injectable solution with lidocaine can be used in patients who have never previously received clodronate treatment.
When switching from other clodronate formulations of 100 mg + 33 mg to
OSTEONORM 200 mg + 40 mg, administration of one vial of OSTEONORM 200 mg + 40 mg every 14 days may be used as an alternative dosing regimen in patients already being treated with one 100 mg vial per week.
Administration of one vial of OSTEONORM 200 mg + 40 mg every 28 days may be used as an alternative dosing regimen in patients already being treated with one 100 mg vial every two weeks.
Alternatively
Oral therapy
OSTEONORM is available only in formulations for intramuscular use and intravenous infusion.
Therefore, for oral therapy, a medicinal product with an oral formulation of clodronate must be prescribed.
Duration
The optimal duration of bisphosphonate treatment for osteoporosis has not been established. The need for continued treatment should be periodically reassessed for each individual patient based on potential benefits and risks, particularly after 5 or more years of use.
Special populations

• Children: The safety and efficacy of the drug in pediatric patients have not been established.
• Elderly: There are no specific dosage recommendations for elderly patients. Clinical studies have included patients aged over 65 years and no age-specific adverse events have been reported in this age group.
• Patients with renal impairment: Clodronate is mainly eliminated via the renal route. Therefore, it should be used with caution in patients with renal impairment.

Parenteral administration:
It is recommended to reduce the clodronate dosage as follows:

Clodronate is recommended to be administered before hemodialysis, the dose should be reduced by 50% on dialysis-free days, and the treatment regimen should be limited to 5 days. It should be noted that peritoneal dialysis poorly removes clodronate from the circulation.

Instructions for use

OSTEONORM 200 mg + 40 mg injectable solution with lidocaine

is for intramuscular use only: to avoid accidental intravascular injection, it is recommended to
aspirate before injecting the medicinal product.
Avoid massaging the injection site.
The solution is incompatible with alkaline solutions or oxidizing solutions.