What it is and what it is used for

for

− if you have kidney problems (you will need reduced dose); − if you have liver problems. Tell your doctor or nurse if flushing and sweating occurs. Your magnesium and calcium blood levels will be monitored during treatment. Your reflexes, breathing and urine output will also be checked while receiving magnesium sulfate. Other medicines and Magnesium Sulfate Injection/Infusion Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines. Medicines which may interact with magnesium sulfate include:  Muscle relaxants e.g. vecuronium  Nifedipine (used to treat high blood pressure or chest pain)  Calcium channel blockers (medicines to treat high blood pressure and chest pain)  Diuretics (medicines that increase the passage of urine) such as thiazides and furosemide  Calcium salts  Digitalis glycosides e.g. digoxin (a medicine used to treat heart problems)  Aminoglycoside antibacterial agents (medicines used to treat bacterial infections)  Barbiturates (medicines for treating anxiety, insomnia)  Opioids (medicines for treating chronic pain) such as morphine  Hypnotics (medicines for sleep disorders).

Pregnancy, breast-feeding and fertility If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before being given this medicine. Magnesium Sulfate Injection/Infusion may be used to treat the fits associated with In adults, adolescents and children pre-eclampsia and eclampsia, a serious − to treat magnesium deficiency (shortage); complications of pregnancy. If you are pregnant − to prevent and treat low levels of magnesium in and you are given Magnesium Sulfate the blood in patients receiving total parenteral Injection/Infusion, your baby's heart rate will be nutrition (nutrients that are infused into the thoroughly monitored and use within 2 hours of bloodstream). delivery will be avoided. Magnesium sulfate can cause foetal skeletal adverse effects when given In pregnant women continuously for more than 5 to 7 days to − to control and prevent seizures in severe pregnant women. In case of prolonged or pre-eclampsia (serious complication of pregnancy repeated use of magnesium sulfate during characterised by high blood pressure and protein pregnancy, your baby will be monitored for in your urine); abnormal calcium or magnesium levels and − to control and prevent recurrent seizures in skeletal adverse effects. You will not receive eclampsia (convulsions as a result of Magnesium Sulfate Injection/Infusion during pre-eclampsia). pregnancy or breast-feeding unless considered essential by your doctor, and it will be given to you under medical supervision. Your doctor will

What you need to know before you take it

assess that the potential benefits outweigh the Magnesium Sulfate Injection/Infusion risks before giving this medicine to you. Magnesium sulfate has no effects on fertility. You should not be given Magnesium Sulfate Injection/Infusion Driving and using machines − if you are allergic to magnesium sulfate, its Magnesium Sulfate Injection/Infusion is unlikely salts or any of the other ingredients of this to affect the ability to drive and use machines. medicine (listed in section 6); However, some people may feel dizzy or drowsy − you have liver failure or condition known as after receiving Magnesium Sulfate injection. If 'hepatic encephalopathy' (impaired brain you experience these side effects, do not to drive function due to liver disease); or use machines. − you have kidney failure or severe kidney problems, or you cannot make or pass urine; Magnesium Sulfate Injection/Infusion contains − you have heart problems or a disease causing sodium muscle weakness and fatigue called This medicinal product contains less than 1 mmol 'myasthenia gravis' (in these cases you should sodium (23 mg) per 1 ml, that is to say essentially not be given magnesium sulfate by injection). 'sodium-free'. Magnesium Sulfate Injection/Infusion contains magnesium (as magnesium sulfate heptahydrate). Magnesium sulfate heptahydrate (hereafter referred to as magnesium sulfate) is a magnesium salt. It is used:

If any of the above apply to you please tell your doctor or nurse before you are given Magnesium Sulfate Injection/Infusion.

How to take it

Warnings and precautions Talk to your doctor, pharmacist or nurse before you are given Magnesium Sulfate Injection/Infusion:

This medicine will be given to you as an injection or infusion into a vein (after being diluted) or as an injection into a muscle.

The following information is intended for healthcare professionals only:

Adults Hypomagnesaemia The dose is strictly individual. As a general guideline, 8-12 g of magnesium sulfate (32-48 mmol Mg2+) can be administered in the first 24 hours followed by 4-6 g (16-24 mmol Mg2+) per day for 3 or 4 days, to replete body stores. Maximum infusion rates should not exceed 2 g/hour (8 mmol Mg2+/hour). The aim should be to maintain serum magnesium concentrations above 0.4 mmol/l.

Magnesium Sulfate 50% w/v Solution for Injection/Infusion Magnesium sulfate heptahydrate Route and method of administration For intravenous injection or infusion or intramuscular injection. Intravenous (IV): DILUTE BEFORE IV USE For intravenous administration, a concentration of 20% or less should be used; the rate of injection not exceeding 1.5 ml/minute of a 10% solution or its equivalent.

Alternatively, 2-4 ml of Magnesium Sulfate 50% w/v solution (4-8 mmol Mg2+) can be injected intramuscularly every 6 hours for 24 hours (4 doses in total). Severe pre-eclampsia or eclampsia Intravenously an initial loading dose of 4-5 g of magnesium sulfate (16-20 mmol Mg2+) diluted to an appropriate volume may be infused. This is followed by a maintenance regimen of either an intravenous (IV) infusion or regular intramuscular (IM) injections as follows:

Intramuscular (IM): Intramuscular injection is painful (avoid if possible). Adults: For deep intramuscular injection in adults, undiluted Magnesium sulfate 50% w/v solution is used. Children: The solution should be diluted to a 20% or less concentration prior to deep intramuscular

• IV maintenance regimen: the loading dose is injection in children. followed by an IV infusion of 1-2 g/hour (4-8 mmol Mg2+/hour); Note: Do not administer into muscles which are emaciated or atrophied. Do not use an injection
• IM maintenance regimen: the loading dose is site that has evidence of infection or injury. followed by regular IM injections of 4-5 g of Dorsogluteal muscle and sciatic nerve should be magnesium sulfate (8-10 ml of undiluted avoided. If the total dose to be administered Magnesium Sulfate 50% w/v solution exceeds 5 ml, the injection volume should be corresponding to 16-20 mmol Mg2+) into divided between more than one deep muscular alternate buttocks every 4 hours, depending on injection site. Use caution in older or thin patients the continuing presence of the patellar reflex who may only tolerate up to 2 ml in a single and adequate respiratory function. injection. If repeating an IM dose, rotate injection sites to avoid injury or discomfort to the muscles. Therapy should continue until paroxysms cease. For instructions on dilution before administration, Paediatric population see 'Instructions for use, disposal and other For deep intramuscular injection in children, handling' below. Magnesium Sulfate 50% w/v solution should be diluted to a 20% or less concentration prior to use. Posology Magnesium sulfate heptahydrate 50% w/v Renal insufficiency (2 mmol Mg2+ in 1 ml). Patients with renal insufficiency should receive Magnesium sulfate heptahydrate 1 g = 98.6 mg or 25-50% of the initial dose recommended for patients 2+ 8.1 mEq or approximately 4 mmol magnesium (Mg ). with normal kidney function. ECG monitoring is 2+ The concentrations of magnesium ions (Mg ) in recommended with high doses and in the elderly. millimoles are given as approximate values. Hepatic impairment Therapeutic levels are reached almost immediately No special dosage instructions are available. with appropriate intravenous doses and within 60 minutes following intramuscular injection.

Your doctor will decide how much magnesium sulfate should be given to you. The usual doses are given below. Adults For magnesium deficiency, you will be given 8-12 g of magnesium sulfate in the first 24 hours followed by 4-6 g/day for 3 or 4 days, to replete body stores. Alternatively, 2-4 ml of undiluted Magnesium Sulfate 50% w/v solution can be injected into a muscle (may be painful) every 6 hours for 24 hours (4 doses in total). For the control and prevention of seizures in severe pre-eclampsia or eclampsia, an initial loading dose of 4-5 g magnesium sulfate diluted to an appropriate volume will be given into your vein. It will be followed by either an infusion into a vein of 1-2 g/hour or regular injections into a muscle of undiluted Magnesium Sulfate 50% w/v solution, until seizures cease.

Hypersensitivity reactions cannot be ruled out. Reporting of side effects If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via Yellow Card Scheme. Website: www.mhra.gov.uk/yellowcard 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.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Frequency not known (cannot be estimated from the available data)  Electrolyte/fluid abnormalities  Breathing difficulties  Feeling or being sick  Drowsiness  Confusion  Slurred speech  Double vision  Loss of tendon reflexes  Irregular heartbeat  Cardiac arrest  Electrocardiogram (ECG) abnormalities  Slowed heart rate  Flushing of the skin and low blood pressure due to dilation of blood vessels  Muscle weakness  Thirst  Coma Low blood calcium levels in pregnant women and their developing babies have been reported extremely rarely with high doses of magnesium sulfate (see 'Pregnancy, breast-feeding and fertility').

Elderly Parenteral magnesium sulfate should be used with caution in the elderly because renal and/or hepatic disorders are more frequent in this age group and the tolerance to adverse effects may be lower. Instructions for use, disposal and other handling For single use only. Discard any unused contents. Can be diluted with 0.9% sodium chloride or 5% glucose solutions. This medicinal product must not be mixed with other medicinal products except those mentioned above. An antidote of injectable calcium gluconate solution should be immediately available. Any unused medicinal product or waste material should be disposed of in accordance with local requirements. Instruction of ampoule opening 1) Hold the ampoule upright. If there is any solution in the upper part of the ampoule, gently tap with your finger to get all the solution to the lower part of the ampoule. 2) Use both hands to open; while holding the lower part of the ampoule in one hand, use the other hand to break off the upper part of the ampoule in the direction away from the coloured point (see the pictures below).

What Magnesium Sulfate Injection/Infusion contains − The active substance is magnesium sulfate heptahydrate. Each 1 ml of solution contains 2 mmol Mg2+ (equivalent to 500 mg magnesium sulfate heptahydrate). Each 2 ml ampoule contains 4 mmol Mg2+ (equivalent to 1 g magnesium sulfate heptahydrate). Each 10 ml ampoule contains 20 mmol Mg2+ (equivalent to 5 g magnesium sulfate heptahydrate). − The other ingredients are sulfuric acid (for pH adjustment), sodium hydroxide (for pH adjustment), water for injections. What Magnesium Sulfate Injection/Infusion looks like and contents of the pack Clear colourless solution, free from visible particles. 2 ml or 10 ml of solution in colourless glass ampoules with red one point cut. Ampoules are packed in polyvinylchloride film liner. Liners are packed into a cardboard box. Pack size: 10 or 100 ampoules Not all pack sizes may be marketed. Marketing Authorisation Holder and Manufacturer AS KALCEKS Krustpils iela 71E, Rīga, LV-1057, Latvia Tel.: +371 67083320 E-mail: [email protected] This leaflet was last revised in 03/2022 If this leaflet is difficult to see or read, please contact: Local safety officer (UK), email: [email protected] 15.03.2022. HUK/I/50/3

would normally not be longer than 24 hours at 2 to 8°C, unless dilution has taken place in controlled and validated aseptic conditions. Overdose Symptoms Intravenous magnesium infusions can result in hypermagnesaemia even in the presence of normal kidney function. Clinical signs of overdose will be those of hypermagnesaemia. Patients with renal failure and metabolic derangements develop toxicity at lower doses. Disappearance of the deep tendon reflex is a useful clinical sign to detect the onset of magnesium intoxication. Magnesium intoxication is manifested by a sharp drop in blood pressure and respiratory paralysis. The potential symptoms of hypermagnesaemia are as follows: Magnesium levels mg/dl mEq/l mmol/l <1.2 1.2-1.8 1.8-2.5 2.5-5.0 5.0-7.0

7.0-12 Shelf life Shelf life after first opening: The medicinal product should be used immediately after opening the ampoule. Shelf life after dilution: Chemical and physical in-use stability has been demonstrated for 72 hours at 25°C and 2 to 8°C after dilution with 0.9% sodium chloride or 5% glucose solution. From a microbiological point of view, 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

>12

Manifestation of overdose symptoms Tetany <1 <0.5 Seizures Arrhythmias 1.0-1.5 0.5-0.75 Neuromuscular irritability Hypocalcaemia Hypokalaemia 1.5-2.1 0.75-1.05 Normal magnesium level 2.5-5.0 1.05-2.1 Typically asymptomatic Lethargy Drowsiness 4.2-5.8 2.1-2.9 Flushing Nausea and vomiting Diminished deep tendon reflex Somnolence Loss of deep tendon 5.8-10 2.9-5 reflexes Hypotension ECG changes Complete heart arrest >10 >5 Apnoea Paralysis Coma

Treatment In symptomatic hypermagnesaemia, administration of calcium, usually at a dose of 100 to 200 mg intravenously over 5 to 10 min, antagonizes the toxic effects of magnesium. In patients with severe renal dysfunction, peritoneal dialysis or haemodialysis will rapidly and effectively lower serum magnesium levels.

How to store it

Magnesium Sulfate Injection/Infusion Keep this medicine out of the sight and reach of children. Do not freeze.

Patients with kidney problems Patients with kidney problems will be given a reduced dose.

Do not use this medicine after the expiry date which is stated on the label and carton after {EXP}. The expiry date refers to the last day of that month.

Patients with liver problems There are no special dosage instructions.

Do not use this medicine if you notice any visible signs of deterioration (e.g. particles).

Elderly Caution should be observed as kidney and/or liver disorders and side effects are more likely in this age group.

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.

Use in children In children, Magnesium Sulfate 50% w/v solution, appropriately diluted prior to use, may be given as an injection into a muscle.

Contents of the pack and other information

If you are given too much Magnesium Sulfate Injection/Infusion As this medicine will be given to you by a doctor or nurse, it is unlikely that you will be given too much. However, tell your doctor or nurse if you have any concerns. If you forget to be given Magnesium sulfate Injection/Infusion It is unlikely that you will miss a dose as your doctor or nurse will be giving it to you. You should not receive a double dose if you have missed one. Ask your doctor or nurse when you should have the next dose.