MOTICLOD 100 mg /3,3 Ml Injectable Solution

Зміст інструкції

1. MOTICLOD 100 mg/3.3 ml injectable solution, 300 mg/10 ml infusion solution

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MOTICLOD 100 mg/3.3 ml injectable solution, 300 mg/10 ml infusion solution

Disodium Clodronate
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PHARMACOTHERAPEUTIC CATEGORY
Drug acting on bone mineralization.

THERAPEUTIC INDICATIONS
Tumor-related osteolysis. Multiple myeloma, primary hyperparathyroidism.
Prevention and treatment of postmenopausal osteoporosis.

CONTRAINDICATIONS
Hypersensitivity to the active substance or excipients.
Concomitant treatments with other bisphosphonates

PRECAUTIONS FOR USE
Administration by intravenous route must be carried out by slow infusion (2-3 hours) in
0.9% NaCl or 5% glucose solution.

INTERACTIONS
Concomitant use with other bisphosphonates is contraindicated.
The simultaneous use of clodronate with non-steroidal anti-inflammatory drugs (NSAIDs), more often with
diclofenac, has been associated with renal dysfunction.
Due to the increased risk of hypocalcemia, caution should be exercised in case of concomitant administration
of clodronate with aminoglycosides.
It has been reported that the concomitant use of estramustine phosphate with clodronate increases the
serum concentration of estramustine phosphate by up to 80%.
Clodronate forms complexes with divalent cations that are poorly soluble in water. Therefore, clodronate
should not be administered intravenously with solutions containing divalent cations (e.g., Ringer's solution).
From a chemical point of view, the content of the vials is incompatible with alkaline or oxidizing solutions.
Clodronate forms complexes with divalent ions and therefore should not be mixed with solutions
containing calcium (e.g., Ringer's solutions).

SPECIAL WARNINGS
During treatment with clodronate, adequate fluid intake must be maintained. This is
particularly important when the administration of clodronate occurs by intravenous route and in
patients with hypercalcemia or renal insufficiency.
Renal function must be monitored before and during treatment by measuring levels of
serum creatinine, calcium and phosphate.
In clinical studies, asymptomatic and reversible increases in transaminases have occurred, without changes
in other liver function tests. Monitoring of transaminases is recommended (see also
paragraph “Undesirable Effects”).
Since the drug is predominantly eliminated by the kidneys, caution is advised in the treatment of
patients with renal insufficiency (see dosage adjustments in the paragraph “Dosage, method and time of
administration”), especially when the drug is administered intravenously. In such
cases, the use of clodronate should be carried out only after careful evaluation of the risk/benefit ratio and
frequent monitoring of renal function indices.
Intravenous administration of doses significantly higher than those recommended can cause
severe kidney damage, especially if the infusion rate is too high.
Osteonecrosis of the jaw and/or mandible, generally associated with tooth extraction and/or
local infection (including osteomyelitis), has been reported in cancer patients undergoing treatment with regimens
including bisphosphonates administered both intravenously and orally. Many of these
patients were also treated with chemotherapy and corticosteroids. Osteonecrosis of the jaw and/or
mandible has also been reported in patients with osteoporosis treated with oral bisphosphonates.
Before starting treatment with bisphosphonates in patients with concomitant risk factors (such as
cancer, chemotherapy, radiotherapy, corticosteroids, poor oral hygiene), the need for a dental examination with appropriate preventive dental procedures should be considered.
During treatment, these patients should, if possible, avoid invasive dental procedures. In
patients who have developed osteonecrosis of the jaw during bisphosphonate therapy, dental surgery may exacerbate the condition. For patients who require dental surgery, there are no
data available to suggest that discontinuation of bisphosphonate treatment reduces the risk
of osteonecrosis of the jaw and/or mandible.
The physician's clinical judgment must guide the management program for each patient, based on
the individual assessment of the risk/benefit ratio.
Moticlod 300 mg/ml solution for infusion contains 47.7 mg of sodium per dose. This must be
considered in patients on a controlled sodium diet.
Since safety of use has not been established, the product is not recommended during
pregnancy and breastfeeding.
The product does not impair the ability to drive vehicles and operate machinery.

Fertility, Pregnancy and Lactation

Fertility
In animal studies, clodronate does not cause fetal damage, but high doses reduce male fertility.
There are no clinical data on the effect of clodronate on human fertility.

Pregnancy
Although clodronate crosses the placental barrier in animals, it is not known whether it crosses into the fetus in humans. Furthermore, it is not known whether clodronate can cause fetal harm or affect reproductive function in humans. There is only a limited amount of data on the use of clodronate
in pregnant women. Moticlod is not recommended during pregnancy and in women of childbearing potential
not protected by effective contraceptive therapy.

Lactation
It is not known whether clodronate is excreted in human milk. A risk to the infant cannot be excluded. Therefore, breastfeeding should be discontinued during treatment with Moticlod.

Effects on ability to drive and operate machines
The drug has no effects on the ability to drive and operate machinery.
KEEP THE MEDICINE OUT OF REACH OF CHILDREN.

DOSAGE, METHOD AND DURATION OF ADMINISTRATION
Clodronate is predominantly eliminated by the kidneys. Therefore, during treatment with
Clodronate, adequate fluid intake is necessary.

Tumor-related osteolysis - Multiple myeloma - Primary hyperparathyroidism
The dosage regimen should be considered as a guideline and can therefore be adapted to the needs
of the individual patient.
a) Attack phase:

• 200 - 300 mg/day in a single administration by slow intravenous route for 3-8 days depending on the trend of clinical and laboratory parameters (calcemia, hydroxyprolinuria, etc.) b) Maintenance phase: 100 mg/day intramuscularly for 2-3 weeks. These cycles can be repeated at variable intervals depending on the evolution of the disease. Periodic evaluation of bone resorption parameters can usefully guide therapeutic cycles.

Prevention and treatment of postmenopausal osteoporosis
The dosage depending on the clinical picture and mineralometric values can vary as reported below:
Intramuscularly 100 mg every 7 – 14 days or by intravenous infusion 200 mg every 3 – 4
weeks, for 1 year or more depending on the patient's conditions.
The optimal duration of treatment with bisphosphonates for osteoporosis has not been established. The need
for continuous treatment must be re-evaluated in each individual patient periodically based on
potential benefits and risks, in particular after 5 or more years of use.

• Children The safety and efficacy of the drug in pediatric patients have not been established
• Elderly There are no specific dosage recommendations for the drug for the elderly. Clinical studies have included patients over 65 years of age and no specific adverse events have been reported for this age group.

Intravenous infusion (only for short-term therapies)
During intravenous treatment with Moticlod, adequate hydration must be ensured.

• Patients with renal insufficiency It is recommended to reduce the dosage of clodronate as follows:

It is recommended to administer clodronate before hemodialysis, to reduce the dose by 50% on non-dialysis days and to limit the treatment regimen to 5 days. It should be noted that peritoneal dialysis
removes clodronate poorly from the circulation.

OVERDOSAGE
Although there is no experience of overdose, it is theoretically possible that high
quantities of product may induce hypocalcemia. In such cases, treatment should consist of
correction of hypocalcemia by adequate dietary supplementation or, in severe cases, by
intravenous administration of calcium.
If alterations in renal function occur due to the formation of calcium aggregates, therapy should aim to restore
functionality itself.
One case of uremia and liver damage has been reported after accidental ingestion of 20,000 mg (50 x
400 mg) of clodronate.

• Symptoms Increased serum creatinine and renal dysfunction have been reported with high doses of clodronate administered intravenously.
• Treatment

Treatment of overdose should be symptomatic. Adequate
hydration should be ensured, and renal function and serum calcium should be monitored.

POSSIBLE SIDE EFFECTS
Rarely, an unusual fracture of the femur may occur, particularly in patients undergoing long-term treatment for
osteoporosis. Contact your doctor if you experience pain, weakness or discomfort in the thigh,
hip or groin as this may be an early indication of a possible femur fracture.
In patients treated with regimens including bisphosphonates administered primarily by
intravenous route, osteonecrosis of the jaw and/or mandible has been reported, generally associated with
tooth extraction and/or local infection (including osteomyelitis) (see also paragraph “Special Warnings”). Most
reports concern cancer patients, but cases have also occurred in patients treated
for osteoporosis. In rare circumstances, bisphosphonates (including clodronate) have been associated with visual and ocular disturbances. If such disorders occur, treatment should be discontinued and
refer to an ophthalmologist.
The most commonly reported reaction is diarrhea, which is usually mild and more frequent with
higher dosages.
These adverse reactions can occur with both oral and intravenous treatment,
although their frequency may differ.

* In patients with metastases, these may also be due to liver or
bone involvement.
** Usually mild
The most appropriate MedDRA term is used to describe a reaction, its
synonyms and related conditions.
Very rare

• Contact your doctor if you experience ear pain, ear discharge and/or ear infection. These episodes may be signs of bone damage to the ear.

Post-marketing experience

• Respiratory, thoracic and mediastinal disorders Impairment of respiratory function in patients with aspirin-sensitive asthma. Hypersensitivity reactions manifesting as respiratory disorders.
• Renal and urinary disorders

Renal insufficiency (increased serum creatinine and proteinuria), severe renal damage especially
after rapid intravenous infusion of high doses of clodronate (for instructions on dosage see
paragraph “Dosage, method and duration of administration”, chapter “Patients with renal insufficiency”).
Isolated cases of renal failure, rarely with fatal outcome, have been reported especially with the concomitant use
of NSAIDs, more frequently diclofenac.

• Musculoskeletal and connective tissue disorders

Isolated cases of osteonecrosis of the jaw have been reported, primarily in patients who had been
previously treated with amino-bisphosphonates such as zoledronate and pamidronate (see also
paragraph “Special warnings”). Severe bone, joint and/or muscle pain has been reported in patients taking clodronate.
However, such reports have been infrequent and, in placebo-controlled randomised studies, no differences appear
between patients treated with placebo or with clodronate. The onset of symptoms varies from days to several months
after the start of therapy with clodronate
Eye disorders
During post-marketing experience with clodronate, cases of uveitis have been reported. The following
reactions have been reported with other bisphosphonates: conjunctivitis, episcleritis and scleritis. Conjunctivitis
has only been reported with clodronate in one patient undergoing concomitant treatment with another bisphosphonate.
So far, episcleritis and scleritis have not been reported with clodronate (adverse reaction of the bisphosphonate class).
It is important to inform your doctor of the appearance of any undesirable effects, even if not described in the

EXPIRY DATE AND STORAGE
Expiry date: see the expiry date printed on the packaging
The expiry date refers to the product in intact packaging, correctly stored.

Warning: do not use the medicine after the expiry date printed on the packaging.
Medicines should not be disposed of via wastewater or household waste. Ask your
pharmacist how to dispose of medicines you no longer use. This will help protect
the environment.
Keep the medicine out of the reach and sight of children.
COMPOSITION
MOTICLOD 100 mg/3.3 ml injectable solution
Each 3.3 ml vial contains

Active ingredient
Disodium clodronate tetrahydrate 125 mg equivalent to disodium clodronate 100 mg

Excipients
sodium bicarbonate, water for injections

MOTICLOD 300 mg/10 ml solution for intravenous infusion
Each 10 ml vial contains

Active ingredient
Disodium clodronate tetrahydrate 375 mg equivalent to disodium clodronate 300 mg

Excipients
sodium bicarbonate, water for injections

PHARMACEUTICAL FORM AND CONTENT
100 mg/3.3 ml injectable solution. 6 vials of 3.3ml.
100 mg/3.3 ml injectable solution. 12 vials of 3.3ml.
300 mg/10 ml solution for infusion. 6 vials of 10ml.

MARKETING AUTHORISATION HOLDER
S.F. Group S.r.l.
Via Tiburtina, 1143 – 00156 Rome

PRODUCER
Lab. It. Biochim. Farm.co LISAPHARMA S.p.A.
Via Licinio, 11 – 22036 ERBA (CO)

OF THE MEDICINAL PRODUCT