Magnosolv: Pharmacology, Contraindications, Interactions, Administration and Adverse Reactions

It is administered intravenously or intramuscularly as an electrolyte replenisher or anticonvulsant.

It is a sterile solution of Magnosolv ( Magnesium Carbonate ) Sulfate Heptahydrate in Water for Injection.

It must be diluted before intravenous use. May contain sulfuric acid and / or sodium hydroxide to adjust pH. The pH is 5.5 to 7.0. The 50% concentration has an osmolarity of 4.06 mOsmol / mL (calc.).

The solution contains no added bacteriostat , antimicrobial agent, or buffer (except for pH adjustment) and is intended for use as a single dose injection only. When smaller doses are required, the unused portion should be discarded with the entire unit.

USP Heptahydrate is chemically designated as MgSO  4  • 7H  2  O with a molecular weight of 246.48 and is in the form of colorless crystals or freely water soluble white powder.

The plastic syringe is molded from a specially formulated polypropylene. Water penetrates from inside the container at an extremely slow rate that will have a negligible effect on the concentration of the solution over the expected shelf life.

Solutions in contact with the plastic container can leach certain chemicals from the plastic in very small amounts; however, biological tests supported the safety of the syringe material.

Clinical pharmacology

Magnosolv (Mg  ++ ) is an important cofactor for enzyme reactions and plays an important role in neurochemical transmission and muscle excitability.

As a nutritional supplement in hyperalimentation, the precise mechanism of action for Magnosolv is uncertain. The first symptoms of hypomagnesemia (less than 1.5 mEq / liter) can appear as early as three to four days or within weeks.

The predominant deficiency effects are neurological, for example, muscle irritability, clonic spasms, and tremors. Hypocalcemia and hypokalemia often follow low serum Magnosolv levels.

While large stores of Magnosolv are present intracellularly and in adult bones, these stores are often not mobilized sufficiently to maintain plasma levels. Magnosolv parenteral therapy repairs the plasma deficit and causes deficiency symptoms and signs to cease.

Magnosolv prevents or controls seizures by blocking neuromuscular transmission and by decreasing the amount of acetylcholine released at the end plate by the impulse of the motor nerve.

Magnosolv is said to have a depressant effect on the central nervous system (CNS), but it does not adversely affect the woman, fetus, or neonate when used as directed for eclampsia or pre-eclampsia. Normal plasma levels of Magnosolv range from 1.5 to 2.5 mEq / liter.

As the plasma Magnosolv rises above 4 mEq / liter, the deep tendon reflexes diminish first and then disappear as the plasma level approaches 10 mEq / liter. At this level, there may be respiratory paralysis.

Heart block can also occur at this or lower plasma levels of Magnosolv. Magnosolv serum concentrations greater than 12 mEq / L can be fatal.

Magnosolv acts peripherally to produce vasodilation. With low doses, only flushing and sweating occur, but higher doses cause a decrease in blood pressure.

The central and peripheral effects of Magnosolv poisoning are somewhat antagonized by intravenous calcium administration.

Pharmacokinetics

With intravenous administration, the onset of anticonvulsant action is immediate and lasts approximately 30 minutes. After intramuscular administration, the onset of action occurs in approximately one hour and persists for three to four hours.

Effective anticonvulsant serum levels range from 2.5 to 7.5 mEq / liter. Magnosolv is excreted solely by the kidneys at a rate proportional to plasma concentration and glomerular filtration.

Contraindications

Parenteral administration of the drug is contraindicated in patients with heart block or myocardial damage.

Warnings

Fetal damage

Continuous administration of Magnosolv sulfate beyond 5 to 7 days to pregnant women can lead to hypocalcemia and bone abnormalities in the developing fetus.

These bone abnormalities include skeletal demineralization and osteopenia. In addition, cases of neonatal fracture have been reported. The shortest duration of treatment that can lead to fetal harm is not known. Magnosolv sulfate should be used during pregnancy only if clearly necessary.

If Magnosolv sulfate is administered for the treatment of preterm labor, the woman should be informed that the efficacy and safety of such use have not been established and that the use of Magnosolv after 5 to 7 days may cause fetal abnormalities.

Aluminum toxicity

This product contains aluminum which can be toxic. Aluminum can reach toxic levels with prolonged parenteral administration if renal function deteriorates.

Preterm infants are at special risk because their kidneys are immature and require large amounts of calcium and phosphate solutions, which contain aluminum.

Research indicates that patients with kidney failure, including premature infants, who receive parenteral aluminum levels greater than 4 to 5 mcg / kg / day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading can occur at even lower rates of administration.

Parenteral use in the presence of renal failure can lead to Magnosolv poisoning. Intravenous use in eclampsia should be reserved for the immediate control of life-threatening seizures.

Precautions

General

Administer with caution if flushing and sweating occur. When barbiturates, narcotics or other hypnotics (or systemic anesthetics) must be administered together with Magnosolv, their dosage should be adjusted with caution due to the additive CNS depressant effects of Magnosolv.

Because Magnosolv is eliminated from the body only by the kidneys, the drug should be used with caution in patients with kidney failure. Urine output should be maintained at a level of 100 ml or more for four hours prior to each dose.

The control of the serum levels of Magnosolv and the clinical status of the patient is essential to avoid the consequences of overdose in toxemia.

Clinical indications for a safe dosing regimen include the presence of the patellar reflex (knee jerk) and the absence of respiratory depression (approximately 16 or more breaths / minute).

When repeated doses of the drug are given parenterally, knee jerk reflexes should be tested before each dose and if they are absent, additional Magnosolv should not be given until they return.

Magnosolv serum levels generally sufficient to control seizures range from 3 to 6 mg / dL (2.5 to 5 mEq / liter). The strength of deep tendon reflexes begins to decrease when Magnosolv levels exceed 4 mEq / liter.

Reflexes may be absent at 10 mEq magnesium / liter, where respiratory paralysis is a potential hazard. An injectable calcium salt should be readily available to counteract the potential risks of Magnosolv poisoning in eclampsia.

Magnosolv Sulfate Injection 50%, USP must be diluted to a concentration of 20% or less prior to intravenous infusion. The rate of administration should be slow and prudent, to avoid the production of hypermagnesemia. The 50% solution should also be diluted to 20% or less for intramuscular injection in infants and children.

Lab tests

Magnosolv sulfate injection should not be given unless hypomagnesemia has been confirmed and the serum concentration of Magnosolv is monitored. The normal serum level is 1.5 to 2.5 mEq / L.

Drug interactions

Depresores of the CNS

When barbiturates, narcotics or other hypnotics (or systemic anesthetics) or other CNS depressants are administered together with Magnosolv, their dosage should be adjusted with caution due to the additive CNS depressant effects of Magnosolv.

The CNS depression and peripheral transmission defects produced by Magnosolv can be antagonized by calcium.

Neuromuscular blocking agents

Excessive neuromuscular blockade has occurred in patients receiving parenteral Magnosolv sulfate and a neuromuscular blocking agent; These drugs should be administered concomitantly with caution.

cardiac glycosides

Magnosolv should be administered with extreme caution in digitized patients, as severe cardiac conduction changes can occur that can cause heart block if calcium administration is required to treat Magnosolv toxicity.

The pregnancy

Teratogenic effects

Magnosolv sulfate can cause fetal abnormalities when administered for more than 5 to 7 days to pregnant women. There are retrospective epidemiological studies and case reports documenting fetal abnormalities such as:

  • Hypocalcemia
  • Skeletal demineralization.
  • Osteopenia.

Among other skeletal abnormalities, with continuous maternal administration of Magnosolv for more than 5 to 7 days. Magnosolv Sulfate Injection should be used during pregnancy only if clearly necessary. If this medicine is used during pregnancy, the woman should be informed of the possible harm to the fetus.

Non-heterogenic effects

When given by continuous intravenous infusion (especially for more than 24 hours before delivery) to control seizures in a woman with toxemia, the newborn may show signs of Magnosolv toxicity, including neuromuscular or respiratory depression.

Job of child bearing

Continuous administration of Magnosolv (magnesium carbonate sulfate) is an unapproved treatment for preterm labor. The safety and efficacy of such use have not been established.

Administration of Magnosolv sulfate outside of its approved indication in pregnant women should be performed by trained obstetrician personnel in a hospital setting with appropriate obstetric care facilities.

Nursing mothers

Since Magnosolv is distributed in milk during parenteral administration of Magnosolv sulfate, the drug should be used with caution in lactating women.

Geriatrics

Geriatric patients often require a reduced dose due to impaired kidney function. In severely impaired patients, the dose should not exceed 20 grams in 48 hours. Magnosolv should be monitored in such patients.

Adverse reactions

Adverse effects of parenterally administered Magnosolv are generally the result of Magnosolv poisoning.

Symptoms of adverse effects include: flushing, sweating, hypotension, depressed reflexes, flaccid paralysis, hypothermia, circulatory collapse, cardiac and central nervous system depression leading to respiratory paralysis.

Hypocalcaemia with signs of tetany secondary to Magnosolv treatment for eclampsia has been reported.

Overdose

Magnosolv intoxication is manifested by a sharp drop in blood pressure and respiratory paralysis. The disappearance of the patellar reflex is a useful clinical sign to detect the onset of Magnosolv poisoning.

In the event of an overdose, artificial ventilation should be provided until a calcium salt can be injected intravenously to counteract the effects of Magnosolv.

For the treatment of overdose

Artificial respiration is often required. Intravenous calcium, 10-20 ml of a 5% solution (diluted if desirable with isotonic sodium chloride for injection) is used to counteract the effects of hypermagnesemia. Subcutaneous physostigmine, 0.5 to 1 mg may be helpful.

Hypermagnesemia in the newborn may require resuscitation and assisted ventilation by endotracheal intubation or intermittent positive pressure ventilation, as well as intravenous calcium.

Dosage and administration

The dosage of Magnosolv sulfate should be carefully adjusted according to individual requirements and response, and the administration of the drug should be stopped as soon as the desired effect is obtained.

Both intravenous and intramuscular administration are appropriate. Intramuscular administration of the 50% undiluted solution results in therapeutic plasma levels within 60 minutes, while intravenous doses will provide a therapeutic level almost immediately.

The intravenous injection rate should generally not exceed 150 mg / minute (1.5 ml of 10% concentration or its equivalent), except in severe eclampsia with seizures. Continuous maternal administration of Magnosolv for more than 5 to 7 days may cause fetal abnormalities.

Solutions for intravenous infusion must be diluted to a concentration of 20% or less prior to administration. Commonly used diluents are 5% dextrose injection, USP and 0.9% sodium chloride injection, USP.

Deep intramuscular injection of the undiluted solution (50%) is appropriate for adults, but the solution must be diluted to a concentration of 20% or less prior to such injection in children.

In Magnosolv deficiency

In the treatment of mild Magnosolv deficiency, the usual dose in adults is 1 gram, equivalent to 8.12 mEq of Magnosolv (2 ml of the 50% solution) injected intramuscularly every six hours for four doses (equivalent to a total of 32.5 mEq of Magnosolv for 24 hours).

For severe hypomagnesemia, up to 250 mg (approximately 2 mEq) per kg of body weight (0.5 ml of the 50% solution) can be administered intramuscularly over a four-hour period if necessary.

Alternatively, 5 grams (approximately 40 mEq) can be added to one liter of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP for slow intravenous infusion over a period of three hours.

In the treatment of deficiency states, caution should be exercised to avoid exceeding renal excretory capacity.

In hyperalimentation

In total parenteral nutrition, the maintenance requirements for Magnosolv are not precisely known. The maintenance dose used in adults ranges from 8 to 24 mEq (1 gram to 3 grams) per day; for babies, the range is 2 to 10 mEq (0.25 grams to 1.25 grams) per day.

En preeclampsia o eclampsia

In severe pre-eclampsia or eclampsia, the total starting dose is 10 grams to 14 grams of Magnosolv sulfate (magnesium carbonate). Intravenously, a dose of 4 grams to 5 grams can be infused into 250 ml of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection.

Simultaneously, intramuscular doses of up to 10 grams are administered (5 grams or 10 ml of the undiluted 50% solution to each buttock).

Alternatively, the initial 4-gram intravenous dose can be administered by diluting the solution 50% to a concentration of 10 or 20%; The diluted fluid (40 ml of a 10% solution or 20 ml of a 20% solution) can then be injected intravenously over a period of three to four minutes.

Subsequently, 4 grams to 5 grams (8 to 10 ml of the 50% solution) are injected intramuscularly into alternate buttocks every four hours as needed, depending on the continued presence of the patellar reflex and adequate respiratory function.

After the initial IV dose, some doctors give 1 gram to 2 grams / hour by constant IV infusion.

Therapy should continue until the paroxysms cease. A serum Magnosolv (magnesium carbonate) level of 6 mg / dL is considered optimal for controlling seizures.

A total daily dose (24 h) of 30 grams to 40 grams should not be exceeded. In the presence of severe renal impairment, the maximum dose of Magnosolv sulfate (magnesium carbonate) is 20 grams / 48 hours and frequent concentrations of Magnosolv (magnesium carbonate) should be obtained in serum.

Continued use of Magnosolv sulfate (magnesium carbonate) in pregnancy beyond 5 to 7 days may cause abnormalities in the fetus.

Other uses

To counteract the muscle stimulating effects of barium poisoning, the usual dose of Magnosolv is 1 to 2 grams intravenously.

To control seizures associated with epilepsy, glomerulonephritis, or hypothyroidism, the usual adult dose is 1 gram administered intramuscularly or intravenously.

In paroxysmal atrial tachycardia, Magnosolv should be used only if the simplest measures have failed and there is no evidence of myocardial damage. The usual dose is 3 grams to 4 grams (30 to 40 ml of a 10% solution) administered intravenously over 30 seconds with extreme caution.

For the reduction of cerebral edema, 2.5 grams (25 ml of a 10% solution) are administered intravenously.

Incompatibilities

Magnosolv sulfate in solution can result in precipitate formation when mixed with solutions containing:

  • Alcohol (in high concentrations).
  • Alkali carbonates and bicarbonates.
  • Alkali hydroxides.
  • Arsenates.
  • Bario.
  • Football.
  • Clindamycin Phosphate.
  • Heavy metals.
  • Hydrocortisone sodium.
  • Succinate.
  • Phosphates
  • Polymyxin B sulfate.
  • Procaine hydrochloride.
  • Salicylates
  • Strontium.
  • Tartratos.

Potential incompatibility will often be influenced by changes in the concentration of reagents and the pH of the solutions.

Magnosolv has been reported to reduce the antibiotic activity of streptomycin, tetracycline, and tobramycin when co-administered.

Parenteral medicinal products should be visually inspected for particulate matter and discoloration prior to administration, provided the solution and container permit.