Clodronate disodium and lidocaine hydrochloride Ipsopharma: detailed information

Package leaflet: Information for the patient

CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA 200 mg + 40 mg

injectable solution
Clodronate disodium – lidocaine hydrochloride
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 they have the same symptoms as you, because it could be harmful.
If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

What CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA is and what it is used for
What you need to know before using CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA
How to use CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA
Possible side effects
How to store CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA
Contents of the pack and other information

1. What CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA is and what it is used for
CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA is a medicine that contains clodronic acid, an active substance belonging to a group of drugs used to treat bone diseases called bisphosphonates.
CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA is used in women for the prevention and treatment of bone thinning (osteoporosis) after menopause (the period of permanent cessation of menstrual cycles).

2. What you need to know before using CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE

IPSO PHARMA
Do not use CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA:

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 CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA.
If you are allergic to lidocaine or to other amide-type local anesthetics, such as for example: bupivacaine, mepivacaine, ropivacaine, levobupivacaine.
If you suffer from a heart disease causing loss of consciousness (Adam-Stokes syndrome).
If you suffer from 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 suffer from a condition characterized by reduced blood volume (hypovolemia).

The medicine is for intramuscular use only (i.e. to be 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 CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA than you should).

Warnings and precautions

Talk to your doctor or pharmacist before using CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA.

Before and during treatment, your doctor will ask you to undergo blood tests to monitor kidney and liver function (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 kidney problems (see section 3. How to use CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA).

In particular, inform your doctor:

If you have high levels of calcium in your blood.
If you suffer from kidney disease (renal insufficiency).
If you are being treated with CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA for cancer or osteoporosis and are undergoing dental treatment or are scheduled for dental surgery. Also inform your dentist that you are being treated with CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA (see section 4. Possible side effects), as preventive dental treatment may be necessary.
If you suffer from heart diseases (particularly rhythm disorders with slow heart rate and heart failure) or if you have undergone heart surgery.
If you suffer from 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 during treatment you experience weakness or pain in the thigh, hip or groin, as this could be an early sign 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 suffer from respiratory or lung disorders.
If you suffer from a disease causing muscle weakness (myasthenia gravis).
If you have porphyria (a rare inherited blood cell 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 CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA

Inform your doctor or pharmacist if you are taking, have recently taken or might take any other medicine.

This is particularly important if:

You are taking other bisphosphonates, medicines used to treat bone diseases, as concomitant use of CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA with other bisphosphonates is contraindicated (see section 2. Do not use CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA).
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 blood calcium levels 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 circulation longer.
You are taking cimetidine, a medicine mainly used to treat gastritis and gastric ulcer (lesion of the stomach wall); fluvoxamine (a medicine used for depression); antiviral medicines such as ritonavir; medicines for treating infections such as macrolide antibiotics (erythromycin) or other antibiotics such as 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 reduced 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, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before using this medicine.

Pregnancy

Avoid using CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA during pregnancy and if you are of childbearing age and are not using effective contraception (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 CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA, breastfeeding should be discontinued.

Fertility

It is not known whether clodronic acid and lidocaine have effects on human fertility.

Driving and using machines

CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA 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 CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA than you should, avoid driving and operating machinery.

CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA contains sodium

This medicine contains 32 mg of sodium (a key component of table salt) per dose. This corresponds to 1.6% of the maximum daily dietary intake recommended for an adult.

3. How to use CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA

Use this medicine exactly as instructed by your doctor, who 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 Leaflet).

Clodronic acid is mainly eliminated via the kidneys. Therefore, during treatment with clodronic acid, you must drink an adequate amount of fluids.

Method of administration
CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA is for intramuscular use only (i.e. to be injected into a muscle). To avoid accidental intravascular injection, it is recommended to aspirate before injecting the medicine.
Do not massage the injection site.

If you use more CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA than you should
If you accidentally take an excessive dose of CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA, contact your doctor or go immediately to the nearest hospital.

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 lidocaine overdose symptoms may occur:

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

Treatment
Your doctor will manage symptoms with specific therapies.

If you forget to use CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA
Do not take a double dose to make up for the missed dose.

If you stop treatment with CLODRONATE DISODIUM AND LIDOCAINE HYDROCHLORIDE IPSO PHARMA
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 everyone experiences them.
If you experience any visual or eye disturbances during treatment, STOP the treatment immediately 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 death of the jaw and/or maxilla), usually 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):

decrease in blood calcium levels without symptoms (asymptomatic hypocalcaemia),
diarrhoea, nausea, vomiting (usually mild in intensity),
increased transaminase levels in the blood (a test to assess liver function), usually within normal limits.

Uncommon (may affect up to 1 in 1,000 people):

decrease in blood calcium levels with symptoms (symptomatic hypocalcaemia),
increased levels of parathyroid hormone (a hormone that regulates calcium levels) in the blood, associated with low blood calcium,
increased alkaline phosphatase levels in the blood (a test to assess bone and liver conditions),
increased transaminase levels in the blood (a test to assess liver function) more than twice the upper normal limit, without other abnormalities in liver function,
allergic reactions manifesting as skin reactions,
unusual femur fracture (thigh bone), 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 could be an early sign of a possible femur 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 symptoms could indicate bone damage in the ear.

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

inflammation of the conjunctiva, the membrane covering the eye and the inner surface of the eyelids (conjunctivitis);
inflammation of the eye (episcleritis, scleritis, and uveitis).
Episcleritis and scleritis have been reported with other drugs in the same class as clodronic acid (adverse class reaction of 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 CLODRONATO DISODICO E LIDOCAINA CLORIDRATO IPSO PHARMA.

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 CLODRONATO DISODICO E LIDOCAINA CLORIDRATO IPSO PHARMA;
pain or sores in the mouth or jaw and/or maxilla (two facial bones). These may be early signs of serious problems (bone death of the jaw and/or maxilla), usually associated with tooth extraction and/or local infection (see section 2. Warnings and precautions). In most cases, this has occurred in patients with cancer.

Effects related to the injection site

tenderness at the injection site, particularly considering the duration of treatment.

Side effects specific to lidocaine
The following side effects are associated with lidocaine; however, there are insufficient data to determine the frequency of the individual effects listed. Side effects are generally due to either allergic reactions or excessively high blood concentrations caused by accidental injection into a blood vessel and/or overdose.
This may occasionally cause central nervous system excitation and occasional cardiovascular depressive effects (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
Symptoms 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 heart rate (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 breathing 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 quiet sounds (hyperacusis).
Reporting of side effects
If you experience any side effects, 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 https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
Reporting side effects can help provide more information on the safety of this medicine.

5. How to store CLODRONATO DISODICO E LIDOCAINA CLORIDRATO IPSO

PHARMA
Keep this medicine out of the sight and reach of children.
This medicine does not require any special storage conditions.
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 medicines 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 CLODRONATO DISODICO E LIDOCAINA CLORIDRATO IPSO PHARMA contains

The active substances are clodronic acid disodium salt (disodium clodronate) 200 mg and lidocaine hydrochloride 40 mg.
The other components are sodium hydrogen carbonate (see section 2. CLODRONATO DISODICO E LIDOCAINA CLORIDRATO IPSO PHARMA contains sodium), water for injections.

Description of the appearance of CLODRONATO DISODICO E LIDOCAINA CLORIDRATO IPSO PHARMA and contents of the pack
Injectable solution, clear and colourless, in packs of 3 - 6 - 9 - 12 vials for intramuscular use.
Marketing Authorization Holder
Ipso Pharma S.r.l., Via San Rocco 6, 85033 Episcopia (PZ).
Manufacturer
Biomedica Foscama Industria Chimico-farmaceutica S.p.A. - Via Morolense 87 - 03013 Ferentino (FR)
The following information is intended exclusively for physicians or healthcare professionals:
DOSAGE, METHOD AND DURATION OF ADMINISTRATION
The dosage, depending on the clinical condition and mineralometric values, may vary as follows:
CLODRONATO DISODICO E LIDOCAINA CLORIDRATO IPSO PHARMA every 14–28 days, for 1 year or longer depending on the patient's condition.
CLODRONATO DISODICO E LIDOCAINA CLORIDRATO IPSO PHARMA may be used in patients who have never previously received clodronate treatment.
When switching from clodronate 100 mg + lidocaine 33 mg to CLODRONATO DISODICO E LIDOCAINA CLORIDRATO IPSO PHARMA 200 mg + 40 mg, administration of one vial of CLODRONATO DISODICO E LIDOCAINA CLORIDRATO IPSO PHARMA 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 CLODRONATO DISODICO E LIDOCAINA CLORIDRATO IPSO PHARMA 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.
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 years or more of use.
Special populations
Children
The safety and efficacy of the medicinal product in paediatric patients have not been established.
Elderly
There are no specific dosage recommendations for elderly patients. Clinical studies conducted have included patients over 65 years of age, and no age-specific adverse events have been reported in this group.
Patients with renal impairment
Clodronate is primarily eliminated via the kidneys. Therefore, it should be used with caution in patients with renal impairment. It is recommended to reduce the clodronate dosage as follows:

Renal impairment degree: Creatinine clearance, ml/min	Dosage reduction, %
50-80	25
12-50	25-50
<12	50

It is recommended to administer clodronate before hemodialysis, to reduce the dose by 50% on dialysis-free days, and to limit the treatment schedule to 5 days. It should be noted that peritoneal dialysis poorly removes clodronate from the circulation.
The solution is incompatible with alkaline solutions or oxidizing solutions.