Clodronate sodium is incompatible with Hartmann’s and Ringer’s (which contain Ca).
1. Withdraw 1500 mg (5 5-mL ampoules) and add to 500 mL of either NaCl 0.9% or Gluc 5%.
2. The solution should be clear and colourless. Inspect visually for particulate matter or discolor-ation prior to administrdiscolor-ation and discard if present.
3. Give by IV infusion over 4 hours.
Multiple intravenous infusions
Preparation and administrationClodronate sodium is incompatible with Hartmann’s and Ringer’s (which contain Ca).
1. Withdraw the required dose and add to 500 mL of either NaCl 0.9% or Gluc 5%.
2. The solution should be clear and colourless. Inspect visually for particulate matter or discolor-ation prior to administrdiscolor-ation and discard if present.
3. Give by IV infusion over at least 2 hours.
Technical information
Incompatible with Clodronate sodium is incompatible with Hartmann’s and Ringer’s (which contain Ca).
Compatible with Flush: NaCl 0.9%
Solutions: NaCl 0.9%, Gluc 5%
Y-site: No information
pH 3--4.5
Sodium content Negligible
Storage Store below 25C in original packaging.
Stability after preparation
From a microbiological point of view, should be used immediately; however, prepared infusions should be infused within 12 hours of preparation.
168 | Clodronate sodium
Monitoring
Measure Frequency Rationale
Fluid balance Frequently during therapy
* Hydration "Ca diuresis.
* Hydration reduces decline in renal function and
#formation of calcium renal calculi.
U&E, CrCl (or eGFR) Prior to each dose and periodically post dose
* #Renal function has been reported during bisphosphonate therapy -- may require #dose or cessation of therapy.
Serum Ca, PO4, Mg * Stop treatment if #Ca develops.
* Serum Ca determines if further treatment is required.
* PO4and Ca share common control systems.
Disruption to Ca metabolism affects PO4levels.
* #Mg occurs commonly during treatment.
Additional information
Common and seriousundesirable effects
Immediate: Angioedema and bronchospasm have been reported.
Other: Renal dysfunction, transient proteinuria immediately after IV infusion, reversible "parathyroid hormone, lactic acid dehydrogenase, transaminase and alkaline phosphatase, asymptomatic #Ca has been noted infrequently;
symptomatic #Ca is rare, pruritus, urticaria, exfoliative dermatitis, jaw osteonecrosis (see above).
Pharmacokinetics The half-life for elimination from plasma is 2 hours but a second phase with a half-life of 13 hours has been identified (<10% of total urinary excretion takes place during this phase). The substance which is bound to bone is excreted more slowly at a rate corresponding to bone turnover.
Significant drug interactions
Clodronate sodium may "levels or effect (or "side-effects) of estramustine.
Action in case of overdose
Symptoms to watch for: Clinically significant #Ca (paraesthesia, tetany, #BP).
Antidote: Calcium gluconate infusion (see the Calcium gluconate monograph).
Stop administration and give supportive therapy as appropriate. Monitor serum Ca, PO4, Mg, K.
Counselling Not known to affect the patient’s ability to drive or use machinery.
Maintain fluid intake during the hours post infusion.
Inform of symptoms of #Ca (paraesthesia, tetany, muscle cramps, confusion).
Advise patients with risk factors for osteonecrosis of the jaw (see pre-treatment checks) not to undergo invasive dental procedures during treatment.
Risk rating: AMBER Score ¼ 3
Moderate-risk product: Risk-reduction strategies are recommended.
This assessment is based on the full range of preparation and administration options described in the monograph. These may not all be applicable in some clinical situations.
Clodronate sodium | 169
Bibliography
SPC Bonefos concentrate (accessed 10/02/09).
Clonazepam
1 mg/mL solution in ampoules with 1-mL diluent ampoules (WFI)
* Clonazepam is a benzodiazepine with marked antiepileptic properties.
* It is used for the treatment of epilepsy and myoclonus. By the IV route it has a fast onset of action and may be used in the management of status epilepticus.
* Oral antiepileptic agents should be instituted as soon as the oral route becomes available and is clinically indicated.
Pre-treatment checks
* Do not use in respiratory depression; acute pulmonary insufficiency; sleep apnoea syndrome;
marked neuromuscular respiratory weakness including unstable myasthenia gravis.
* Caution in elderly or debilitated patients, respiratory disease, spinal or cerebellar ataxia; history of alcohol or drug abuse, depression or suicidal ideation; avoid sudden withdrawal; myasthenia gravis (avoid if unstable); acute porphyria; hepatic impairment; renal impairment; pregnancy and breast feeding.
* Ensure that resuscitation equipment is available.
Biochemical and other tests (not all are necessary in an emergency situation) Blood pressure
LFTs
Renal function: U, Cr, CrCl (or eGFR)
Dose
Standard dose: 1 mg by slow IV injection or intermittent IV infusion. The dose may be repeated if required.
Continuous IV infusion: the BNF advises that IV infusion is potentially hazardous (particularly if prolonged), calling for close and constant observation, and is best carried out in specialist centres with intensive care facilities. Prolonged infusion may lead to accumulation and delayed recovery.
Dose in hepatic impairment: reduce dose and avoid if severe.
Intravenous injection
Preparation and administrationGive slowly into a large vein to reduce risk of thrombophlebitis.
1. Withdraw the required dose and dilute with an equal volume of WFI (supplied) to give a concentration of 0.5 mg/mL.
2. The solution should be clear and colourless to slightly greenish yellow. Inspect visually for particulate matter or discoloration prior to administration and discard if present.
3. Give by IV injection into a large vein of the antecubital fossa at a maximum rate of 0.5 mg/
minute. (There is a risk of thrombophlebitis if smaller veins or faster rates are used.) 170 | Clodronate sodium | Clonazepam
Intermittent intravenous infusion
Preparation and administration1. Withdraw the required dose and add to a suitable volume of compatible infusion fluid to give a maximum concentration of 3 mg in 250 mL, e.g. add 1 mg to 100 mL NaCl 0.9%.
2. The solution should be clear and colourless to slightly greenish yellow. Inspect visually for particulate matter or discoloration prior to administration and discard if present.
3. Give by IV infusion at a maximum rate of 0.5 mg/minute via volumetric infusion device.
Technical information
Incompatible with Sodium bicarbonate
Compatible with Flush: NaCl 0.9%
Solutions: NaCl 0.9%, Gluc 5%, Gluc-NaCl Y-site: Nil
pH 3.8
Sodium content Nil
Excipients Contains benzyl alcohol, ethanol, propylene glycol (adverse effects seen if renal elimination is impaired and may interact with disulfiram and metronidazole).
Storage Store below 30C in original packaging.
Stability after preparation
Use diluted injection immediately.
Use prepared infusions immediately. Complete the infusion within 2 hours if PVC containers are used, or 12 hours if glass bottles are used.
Monitoring
Measure Frequency Rationale
Seizure frequency and severity
At regular intervals * Monitor for reduction in the frequency and severity to ensure therapeutic effect.
Injection site * Thrombophlebitis may occur (rarely).
Respiration, blood pressure and EEG (where available)
Continuously through administration
* "Drowsiness and CNS depression may occur.
* #BP or apnoea may occur (rarely).
Full blood count Periodically * May cause blood dyscrasias.
* Withdraw therapy if spontaneous bruising or bleeding occurs.
LFTs * Altered LFTs may occur.
Clonazepam | 171
Additional information
Common andserious undesirable effects
Injection/infusion-related: Local: Thrombophlebitis and thrombus formation (particularly if a small vein is used).
Other: Drowsiness, fatigue, dizziness, disorientation, muscle hypotonia, restlessness, confusion, amnesia.
Pharmacokinetics Elimination half-life is 20--60 hours (average 30 hours).
Significant interactions
* The following may "clonazepam levels or effect (or "side-effects):
olanzapine IM (#BP, #pulse, respiratory depression), ritonavir.
* Clonazepam may "levels or effect (or "side-effects) of sodium oxybate (avoid combination).
* Injectable preparation contains ethanol and propylene glycol: may interact with disulfiram and metronidazole.
Action in case of overdose
Symptoms to watch for:"Sedation, respiratory depression, #BP.
Antidote: Flumazenil (use with caution in patients with a history of seizures, head injury or chronic benzodiazepine use including for the control of epilepsy).
Stop administration and give supportive therapy as appropriate.
Counselling May cause transient drowsiness -- if affected do not drive or operate machinery.
Advise women of child-bearing potential to use adequate contraception.
Risk rating: AMBER Score ¼ 3
Moderate-risk product: Risk-reduction strategies are recommended.
This assessment is based on the full range of preparation and administration options described in the monograph. These may not all be applicable in some clinical situations.
Bibliography
SPC Rivotril ampoules (accessed 14/07/08)