MAGNESIUM SULFATE 50% W/V SOLUTION FOR INJECTION OR CONCENTRATE FOR SOLUTION FOR INJECTION OR INFUSI - patient leaflet, side effects, dosage

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Package leaflet: Information for the user

Magnesium sulfate 50% w/v solution for injection or concentrate for solution for injection or infusion

Magnesium

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• – Keep this leaflet. You may need to read it again.

• – If you have any further questions, ask your doctor, or pharmacist or nurse.

• – This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

• – If you get any side effects, talk to your doctor, or pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

The name of your medicine is Magnesium sulfate 50% w/v Solution for injection or concentrate for solution for injection or infusion. In the rest of this leaflet the name of the medicine shall be Magnesium sulfate 50%.

What is in this leaflet

• 1. What Magnesium sulfate 50% is and what it is used for

• 2. What you need to know before you are given Magnesium sulfate 50%

• 3. How Magnesium sulfate 50% is given

• 4. Possible side effects

• 5. How to store Magnesium sulfate 50%

• 6. Contents of the pack and other information

1. what magnesium sulfate 50% is and what it is used for

Magnesium sulfate 50% contains magnesium as magnesium sulfate heptahydrate. Magnesium sulfate heptahydrate is a magnesium salt.

Magnesium sulfate 50% is given:

• To increase the amount of magnesium in the body in conditions where, because of a variety of causes, the blood level of magnesium is below normal (hypomagnesaemia) and especially when it is followed by tetany symptoms.
• For the prevention and control of further fits (seizures) occurring because of very high blood pressure in pregnancy (eclampsia).
• For the prevention and control of fits (seizures) in severe pre-eclampsia.
• For the prevention and treatment of hypomagnesaemia in patients receiving Total Parenteral Nutrition.

2. what you need to know before you are given magnesium sulfate 50%

Do not use Magnesium sulfate 50%:

• If you are allergic to magnesium sulfate and magnesium salts or any of the other ingredients of this medicine (listed in section 6)
• If you have liver problems (particularly in hepatic coma if there is a risk of kidney failure)
• If you have kidney failure or severe kidney problems, or you cannot make or pass urine (anuria)
• If you have heart problems
• If you have a disease causing muscle weakness and fatigue called myasthenia gravis.

Warnings and precautions

Talk to your doctor, or pharmacist or nurse before you are given Magnesium sulfate 50% if:

• You have kidney problems, a reduction in the usual dosage may be appropriate.

Preparationan­dhandling

The 50% w/v solution MUST be diluted before use for IV administration; concentrations up to 20% w/v are usually employed.

Incompatibilities

This medicinal product must not be mixed with other medicinal products/diluents except Glucose 5% or sodium chloride 0.9%.

Magnesium sulfate is incompatible with alkali hydroxides (forming insoluble magnesium hydroxide), alkali carbonates (forming insoluble magnesium carbonate) and salicylates. The activities of streptomycin sulfate and tetramycin sulfate are inhibited by magnesium ions.

Posology and method of administration Treatment of magnesium deficiency in proven hypomagnesaemia

Adults:

Intravenous Route:

Up to 80 mL Magnesium sulfate 50% w/v solution (corresponding to 160 mmol ~ 4 g Mg2+) diluted should be administered by slow intravenous infusion over a period of up to five days and titrated to clinical need. The usual regimen is 16 – 24 mL Magnesium sulfate 50% w/v solution (corresponding to 32 –48 mmol» 0.8 –1.2 g Mg2+) diluted in the first 24 hours followed by 8 – 12 mL Magnesium sulfate 50% w/v solution (corresponding to 16–24 mmol ~ 0.4 – 0.6 g Mg2+) diluted per day for 3 or 4 days. Intramuscular Route:

2 – 4 mL Magnesium sulfate 50% w/v solution (corresponding to 4 – 8 mmol ~ 0.1 – 0.2 g Mg2+) undiluted or 4 – 8 mL of Magnesium sulfate 50% w/v solution diluted to 25% w/v solution can be given intramuscularly every 6 hours for 24 hours (a total of 4 doses).

Children and adolescents:

Neonate

0.2 mL/kg Magnesium sulfate 50% w/v solution (corresponding to 0.4 mmol/kg ~ 0.01 g/kg Mg2+) diluted to 20% w/v solution (i.e. 0.5 mL/kg of a 20% w/v solution) every 6–12 hours as required, to be given by intravenous injection over at least 10 minutes.

• You are taking or using other medicines (see ‘Other medicines and Magnesium sulfate 50%’ below).

Other medicines and Magnesium sulfate 50%

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

Tell your doctor if you are taking any of the following medicines:

• Hypnotics (medicines for sleep disorders) such as nitrazepam or temazepam
• Barbiturates (medicines for anxiety, insomnia) such as amylobarbitone
• Opioids (medicines for chronic pain) such as morphine or codeine
• Muscle relaxants (used during anaesthesia) such as tubocurarine
• Digoxin or other digitalis glycosides (medicines used for the treatment of heart problems)
• Suxamethonium (medicine used for anaesthesia).
• Aminoglycoside antibacterial medicines (medicines used to treat bacterial infections) such as streptomycin.
• Calcium channel blockers (medicines used to treat high blood pressure and chest pain (angina)) such as nifedipine or amlodipine and diuretics (medicines that increase the passage of urine) such as thiazides and furosemide.
• Calcium salts

Pregnancy and breast-feeding

Magnesium sulfate 50% is used for the control and prevention of fits (seizures) related with severe preeclampsia and eclampsia, two serious complications of pregnancy. Magnesium sulfate crosses the placenta. Small amounts of magnesium get into breast milk.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

Your medicine is unlikely to affect your ability to drive or to operate machinery. However, some people may feel dizzy or drowsy when given Magnesium sulfate 50%. If this happens to you, do not drive or operate machinery.

• 3. How Magnesium sulfate 50% is given Magnesium sulfate will be given to you by injection either into a muscle (intramuscularly) or into a vein (intravenously) after being diluted. The dose depends on your individual needs and responses to treatment. Your blood levels will be monitored during treatment. If you have doubts about the treatment or want more information about your medicine or the monitoring procedure, do ask the doctor or nurse.

If you are given more Magnesium sulfate 50% than you should be

As this medicine will be given to you by a doctor or nurse, it is unlikely that you will be given too much. Excessive administration of magnesium leads to the development of hypermagnesaemia, i.e. high blood levels of magnesium. Hypermagnesaemia may only be associated with mild symptoms initially – see “Possible side effects” below – but if treatment is not terminated or efforts made to reduce the blood level, symptoms may become more serious and could lead eventually to coma or cardiac arrest.

Tell the doctor if you are experiencing any side effects or think you may be reacting badly so that he/ she can give appropriate treatment.

If you have already left the medical premises, contact your nearest hospital, doctor or pharmacist.

If you forget to be given Magnesium sulfate 50% It is unlikely that you will miss a dose as your doctor or nurse will be giving it to you.

Child 1 month - 11 years

0.1 mL/kg Magnesium sulfate 50% w/v solution (corresponding to 0.2 mmol/kg ~ 0.005 g/kg Mg2+) diluted to 20% w/v solution (i.e. 0.25 mL/kg of a 20% w/v solution) every 12 hours as required, to be given by intravenous injection over at least 10 minutes.

Adolescent 12–17 years

2 mL Magnesium sulfate 50% w/v solution (corresponding to 4 mmol ~ 0.1 g Mg2+) diluted to 20% w/v solution (i.e. 5 mL of a 20% w/v solution) every 12 hours as required, to be given by intravenous injection over at least 10 minutes. Elderly:

As for adults. Magnesium sulfate 50% w/v solution should be used with caution in elderly because of often renal impairment in this age group.

Prevention of hypomagnesaemia in patients receiving total parenteral nutrition

Adults:

5 – 10 mL Magnesium sulfate 50% w/v solution (corresponding to 10 – 20 mmol = 0.25 – 0.5 g Mg2+) diluted daily, usual dose 6 mL Magnesium sulfate 50% w/v solution (corresponding to 12 mmol == 0.3 g Mg2+) diluted daily, by intravenous infusion or intramuscular injection.

Neonates and infants (up to 12 months): 0.1 mL/kg Magnesium sulfate 50% w/v solution (corresponding to 0.2 mmol/kg = 0.005 g/kg Mg2+) diluted daily by intravenous infusion.

Children (1 – 13 years) and adolescents (14–18 years):

0.05 mL/kg Magnesium sulfate 50% w/v solution (corresponding to 0.1 mmol/kg ~ 0.0025 g/kg Mg2+) diluted daily by intravenous infusion.

Control and prevention of recurrent seizures in severe pre-eclampsia and eclampsia

Adult women:

Loading dose: An initial IV loading dose of approximately 8 – 10 mL Magnesium sulfate 50% w/v solution (corresponding to 16 – 20 mmol == 0.4 – 0.5 g Mg2+) diluted to an appropriate volume is administered over 5 – 15 minutes followed either by maintenance intravenous infusion or regular IM injections for 24 hours, as follows:

Intravenous maintenance regimen:

The IV loading dose (above) is followed by an infusion of approximately 2 mL Magnesium sulfate 50% w/v solution (corresponding to 4 mmol ~ 0.1 g Mg2+) diluted per hour for at least 24 hours after the last fit.

However, it is important not to have a double dose if you have missed one. Ask your doctor pharmacist or nurse when you should have the next dose.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

4. possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Seek immediate medical help if you have an allergic reaction. This included any of the following symptoms:

• Difficulty in breathing, – slow and/or shallow breathing
• Swelling of your eyelids, face or lips
• Rash or itching especially those covering your whole body

The frequency of side effects is not known (cannot be estimated from the available data).

Nervous System disorders

• Feeling sick (nausea)
• Vomiting
• Drowsiness
• Feeling confused
• Coma
• Slurred speech
• Double vision

Heart problems

• Drop in blood pressure
• Flushing of the skin
• Irregular heart beats
• Heart attack

Other effects

• Loss of the knee jerk reflex
• Muscle weakness
• Feeling thirsty
• Low blood calcium levels in pregnant women and their developing babies have been reported extremely rarely
• Low levels of calcium in your blood. (This may cause you to have pins and needles or twitching muscles)
• Vein irritation
• Tissue damage due to extravasation (medication injected or leaked outside the vein into the surrounding tissue)
• Dilatation of blood vessels
• Pain
• Redness
• Swelling or warmth at the injection site
• Drainage at the injection site
• Continuing bleeding
• Skin infection (cellulitis)
• Abscess (especially near injection site),
• Injury to nearby structures (blood vessels, bones, or nerves)
• Accidental injection into a vein or a bone
• Death of tissue cells (tissue necrosis)
• Poor absorption due to high volume injected.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme, Website: or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

5. how to store magnesium sulfate 50% after dilution, the product should be used immediately. if not used immediately, in-use storage times and conditions prior to use are the responsibilities of the user and would normally not be longer than 48 hours at 23 - 27°c and 2 - 8°c when diluted to a concentration of not more than 200 mg/ml magnesium sulfate heptahydrate in sodium chloride 0.9% or glucose 5%, unless reconstitution/dilution has taken place in controlled and validated aseptic conditions. this medicinal product does not require any special storage conditions.

Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the ampoule and carton after EXP. The expiry date refers to the last day of that month. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. contents of the pack and other information what magnesium sulfate 50% contains

• – The active substance is magnesium as magnesium sulfate heptahydrate. 1 mL of Magnesium sulfate 50% w/v (5 g/10 mL) solution for injection or concentrate for solution for injection or infusion contains 500 mg of magnesium sulfate heptahydrate. Each 10 mL ampoule contains 5 g magnesium sulfate heptahydrate.

• – The other ingredients are water for injections and sulfuric acid.

What Magnesium sulfate 50% looks like and contents of the pack

Magnesium sulfate 50% w/v (5 g/10 mL) solution for injection or concentrate for solution for injection or infusion is a clear, colourless solution. The product is available in 10 mL polypropylene ampoules in packs of 10, 20, and 50 ampoules.

Marketing Authorization Holder and Manufacturer DEMO S.A., PHARMACEUTICAL INDUSTRY, 21st km National Road Athens-Lamia, GR-14568 Krioneri, Attiki, Greece, T.: +30 210 8161802, F.: +30 210 8161587.

This medicinal product is authorised in the Member States of the EEA under the following names:

United Kingdom: Magnesium sulfate 50% w/v Solution for injection or concentrate for solution for injection or infusion Magnesium sulfate/DEMO 50% w/v nuKvo SidAupa yia napaaKsuq svsaipou SiaAuparo^/ SiaAuparo^ npo^ muan Magnesium DEMO 2,0 mmol/ml Losung zur Injektion oder Konzentrat zur Herstellung einer Injektion oder Infusion

This leaflet was last revised in 10/2018.

If this leaflet is difficult to see or read, please contact the following address for help:

Athlone Laboratories, Ballymurray, Co. Roscommon, Ireland, Tel: +353–9066–61109, Email: .

Intramuscular maintenance regimen:

The IV loading dose (above) is immediately followed by deep IM injection of 10 mL Magnesium sulfate 50% w/v solution (corresponding to 20 mmol ~ 0.5 g Mg2+) undiluted. Maintenance therapy is a further 10 mL Magnesium sulfate 50% w/v solution (corresponding to 20 mmol ~ 0.5 g Mg2+) undiluted IM every four hours, continued for 24 hours after the last fit (provided respiratory rate is >16/min, urine output >25 mL/min and knee jerks are present).

Recurrent convulsions: In both IV and IM regimens, a further 4 – 8 mL Magnesium sulfate 50% w/v solution (corresponding to 8 –16 mmol ~ 0.2 – 0.4 g Mg2+) diluted depending on body weight [if less than 70 kg 4 mL Magnesium sulfate 50% w/v solution (corresponding to 8 mmol ~ 0.2 g Mg2+) diluted] are given IV over a period of 5 minutes.

Renal impairment

Magnesium sulfate 50% w/v solution is contraindicated in patients with severe renal impairment. Magnesium sulfate 50% w/v solution should be used with caution in mild to moderate renal impairment. A reduction in dosage to 40 mL Magnesium sulfate 50% w/v solution (corresponding to 80 mmol ~ 2 g Mg2+) diluted over 48 hours may be given.

Patients with impaired liver function

There are no recommended special dosage instructions for patients with impaired liver function because of insufficient data.

Method of administration

Intravenous use in adults and adolescents

Intravenous infusion: For the intravenous route, the 50% w/v solution requires dilution to a concentration of not more than 20% (< 200 mg/ mL magnesium sulfate heptahydrate) – with a suitable diluent, such as Glucose 5% or sodium chloride 0.9%. Infuse via a volumetric infusion device at a rate appropriate to the indication (see posology above).

Intravenous injection: Give by slow IV injection at a rate appropriate to the indication (see posology above).

Intravenous use in children:

Rate of administration should not exceed

0.02 mL/kg/min of appropriately diluted Magnesium sulfate 50% w/v solution (corresponding to 0.04 mmol/kg/min ~ 0.001 g/kg/mi­n Mg2+).

Deep Intramuscular injection (adults only) For the intramuscular route, the 50% w/v solution should be used undiluted or diluted to 25% w/v. If the total dose to be administered exceeds 5 mL, the injection volume should be divided between more than one deep muscular injection site.

For the intramuscular route, use good clinical practice for intramuscular injections. Avoid muscles which are emaciated or atrophied. Avoid the dorsogluteal muscle and sciatic nerve. If the total dose to be administered exceeds 5 mL, the injection volume should be divided between more than one deep muscular injection site. Use caution in older or thin patients who may only tolerate up to 2 ml in a single injection. Do not use an injection site that has evidence of infection or injury. If repeating an intramuscular dose, rotate injection sites to avoid injury or discomfort to the muscles.

Disposal

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Overdose

Signs

Excessive administration of magnesium leads to the development of hypermagnesaemia. Magnesium intoxication is manifested by a sharp drop in blood pressure and respiratory paralysis. Disappearance of the patellar reflex is a useful clinical sign to detect the onset of magnesium intoxication.

Mg plasma concentration (mmol/L)	Symptoms and undesirable effects
2 to 3	nausea, flushing, headache, lethargy, drowsiness, diminished deep tendon reflexes, platelet disaggregation
3 to 5	somnolence, hypocalcemia, absent deep tendon reflexes, hypotension, bradycardia, and ECG changes
> 5	muscle paralysis, respiratory paralysis, coma. In most cases, respiratory failure precedes cardiac collapse
> 7.0	Complete heart block and cardiac arrest

Patients with renal failure and metabolic derangements develop toxicity at lower doses. Treatment

Appropriate action should be taken to reduce the blood level of magnesium. In the event of overdosage, artificial ventilation must be provided until a calcium salt can be injected IV to antagonize the effects of Magnesium.

Neuromuscular blockade associated with hypermagnesaemia may be reversed with calcium salts, such as calcium gluconate, which should be administered intravenously in a dose equivalent to 2.5 to 5 mmol of calcium.