Zinc Sulfate Injection - Indication, Dosage, Precautions, and Pharmacological Aspects

Overview

Zinc sulfate injection is used in adults and kids when they cannot get enough zinc through regular eating or feeding tubes, and it cannot be given by mouth. It is a way to provide the body with zinc when the usual methods are not an option or enough. The Food and Drug Administration (FDA) approved Zinc sulfate injection in 1957.

Drug Group:

Zinc sulfate is a type of compound that falls under metal sulfate compounds. It is made up of Zinc(2+) as the main part. Zinc sulfate is part of a group of inorganic compounds described by the formula ZnSO4(H2O)x.

Available Doses and Dosage Forms:

Zinc Sulfate Injection, USP (unique selling point), comes in a clear, colorless solution available as:

• A 10 mL (milliliter) Pharmacy Bulk Package vial containing 30 mg (milligram) of zinc per 10 mL (3 mg/mL). It is sold in cartons of 25 vials with the NDC 0517-6103-25.

• A 5 mL Pharmacy Bulk Package vial containing 25 mg of zinc per 5 mL (5 mg/mL (milligram per milliliter)). It is sold in cartons of 25 vials with the NDC 0517-8005-25.

The closure of the vial is not made from natural rubber latex.

For Patients

What Is Parenteral Nutrition?

Parenteral nutrition, or PN, involves getting essential nutrients like proteins, carbs, fats, minerals, vitamins, and other important elements through an IV (intravenous). It is for individuals who cannot eat enough or absorb sufficient nutrients through regular food or feeding tubes to stay well-nourished.

How Does Zinc Sulfate Injection Work?

This medicine is a mineral used to treat or prevent low levels of zinc, either on its own or in combination with oral rehydration therapy. It is also applied as a topical astringent. Zinc sulfate injection is an added component in intravenous solutions for TPN (total parenteral nutrition).

What Is the Dosage of Zinc Sulfate Injection?

Zinc Sulfate Injection Concentrations: 1 mg/mL, 3 mg/mL, or 5 mg/mL strengths.

• Pediatric Patients: Typically, the 1 mg/mL concentration is used for children, especially those weighing less than 12 kg (kilogram), and the dosage for pediatric patients varies by age and weight.

• Dosage Determination: Doctors personalize the dose based on the patient's condition, nutritional needs, and oral/enteral Zinc intake.

• Adult Dosage: Usually 3 mg daily, but patients with intestinal issues may need more.

• Monitoring: It is essential to track Zinc levels and signs of deficiency, particularly in children.

• Strengths: 1 mg/mL, 3 mg/mL, and 5 mg/mL are available in Pharmacy Bulk Package vials.

How Effective Is Zinc Sulfate Injection?

Zinc Sulfate injection is meant to be added to suitable intravenous fluids or complete parenteral nutrition solutions. It is used to:

• Prevent zinc deficiency.

• Treat zinc deficiency.

• Poor growth.

• Skin issues.

• Hair loss.

• Reproductive problems.

• Slow wound healing.

What Are the Things to Inform the Doctor Before Taking the Zinc Sulfate Injection?

Before taking Zinc sulfate Injection, make sure to talk to the doctor if a person:

• Has allergies to medications, foods, preservatives, or dyes.

• Has kidney disease or low copper levels in their blood.

• If a person is pregnant or planning to become pregnant or breastfeeding. The doctor can help weigh the risks and benefits.

• Let the doctor know about all the medications the person is taking, including ones they buy without a prescription. Some medicines might not go well with Zinc sulfate, so it is essential to discuss this with the doctor or pharmacist for more information on what to be careful about.

How Is Zinc Sulfate Injection Administered?

• Zinc sulfate should only be administered by a doctor or nurse.

• It must be diluted before use and should not be taken by mouth as it can be harmful and cause burns in the mouth.

• It is mixed with an IV solution and then given through a vein.

• The doctor will determine the dose and duration of this medicine based on the person’s medical condition and factors like weight.

• Be cautious to prevent spills on the skin or the eyes because they can cause harm. If this happens, wash the area thoroughly.

What Are the Side Effects of Zinc Sulfate Injection?

No zinc-related adverse reactions are present for intravenously administered parenteral nutrition solutions within recommended doses.

Adverse Reactions Are Challenging to Estimate Frequency:

• Pulmonary embolism due to pulmonary vascular precipitates.

• Vein damage and thrombosis (blockage of blood in veins or arteries).

• Aluminum toxicity.

Adverse Reactions Associated with Zinc-containing Products Administered Through Other Routes:

• Copper deficiency.

• Hypersensitivity reactions.

Dietary Considerations:

• Do not have Zinc along with milk or dairy products.

• If the food contains phosphorus, separate its use from zinc sulfate injection at least two hours before and after taking zinc.

• Avoid pairing Zinc sulfate with bran and high-fiber foods.

• For best absorption, take Zinc sulfate at least 2 hours before or after eating foods high in fiber.

• Taking Zinc sulfate on an empty stomach is best.

• Try to take Zinc sulfate at least one hour before and two hours after eating.

• If Zinc sulfate upsets the stomach, take it with food.

Missed Dose:

1. For Oral Products: If someone misses a dose, they should take it when they remember. But if it is almost time for the next dose, just take it. Do not take two doses together or extra doses.

2. For Injections: If a person misses a dose, contact the doctor to know what to do next.

Overdose:

• Large oral intake of Zinc sulfate (around 30 to 44 grams) has led to fatal cases with symptoms like nausea, vomiting, dehydration, electrolyte imbalances, dizziness, abdominal pain, fatigue, and lack of coordination.

• Intravenous doses of one to two mg zinc per kg body weight in adult leukemia patients have not shown harmful effects.

• Normal blood zinc levels range from about 88 to 112 mcg/100 mL; specific levels causing toxic symptoms are unknown.

• Calcium supplements offer protection against zinc toxicity.

Storage:

Zinc sulfate should be stored in the hospital's pharmacy or on the ward in a cool, dry place below 30 degrees Celsius. It is for single use by a person, and any leftover medicine should be discarded afterward. It should only be stored after opening it or used for up to one person.

For Doctors

Indication:

• Acrodermatitis enteropathica (an uncommon genetic illness where the body has trouble absorbing zinc, which can cause gastrointestinal problems, skin sores, and hair loss).

• Acute diarrhea (sudden onset of frequent, loose bowel movements, typically lasting for a short period).

• Zinc deficiency (inadequate consumption of Zinc, illnesses, or malabsorption, which impacts wound healing, immunity, and growth).

• Wilson’s disease (a hereditary condition that causes the body, especially the liver and brain, to become overloaded with copper).

Dose:

Zinc sulfate injection, USP, is available in two formulations:

1. A 10 mL pharmacy bulk package vial containing a clear and colorless solution, providing 30 mg of zinc at a concentration of 3 mg/mL.

2. A 5 mL pharmacy bulk package vial containing a clear and colorless solution delivers 25 mg of zinc at a 5 mg/mL concentration.

Dosing Considerations:

The administration of the ultimate parenteral nutrition solution, incorporating Zinc sulfate injection, should be determined by considering the concentrations of all solution components and adhering to recommended daily nutritional requirements. Before administering the parenteral nutrition solution with Zinc sulfate Injection, address any severe fluid, electrolyte, and acid-base disorders.

Zinc sulfate Injection is available in concentrations of 3 mg/mL or 5 mg/mL of zinc. The dosage of Zinc sulfate injection should be tailored to the patient's clinical status, nutritional demands, and the extent of oral or enteral Zinc intake.

Adults: The recommended dosage is 3 mg/day for metabolically stable patients. However, in closely monitored individuals with conditions such as small bowel fluid loss, excessive stool, or ileostomy output, a higher daily dosage may be necessary.

Pediatric Patients: The recommended dosage is 50 mcg/kg based on age and estimated weight. These dosages are general guidelines applicable to most pediatric patients. Nevertheless, certain patients may require an elevated dosage based on clinical needs.

What Are the Pharmacological Aspects of Zinc Sulfate Injection?

Pharmacodynamics:

Zinc serves as a cofactor for more than 70 enzymes, encompassing alkaline phosphatase, lactic dehydrogenase, and both RNA and DNA ( Ribonucleic acid and Deoxyribonucleic acid) polymerase. Its functions include facilitating wound healing, regulating normal growth rates, maintaining optimal skin hydration, and preserving sensory perception of taste and smell.

Mechanism of Action:

Zinc is a crucial trace element with diverse biological functions. It serves as a cofactor for various enzymes, playing essential roles in the activities of DNA polymerases, RNA polymerases, alcohol dehydrogenase, and alkaline phosphatases. Additionally, zinc acts as a coordinator in the structural folding of proteins, particularly in forming "zinc finger" motifs that interact with various proteins, lipids, and nucleic acids. Furthermore, zinc functions as a catalyst in fundamental biochemical reactions, such as activating substrates of carbonic anhydrase in erythrocytes. Moreover, zinc operates as a signaling mediator, influencing multiple signaling pathways in cellular processes.

Pharmacokinetics:

Distribution:

• More than 85 percent of the body's total zinc is in skeletal muscle and bone.

• Other organs that house significant zinc stores include the liver, kidney, skin, brain, and heart.

• In the blood, zinc is predominantly found within erythrocytes.

• About 80 percent of serum zinc is bound to albumin, with the remaining portion binding to alpha2-macroglobulin and amino acids.

Elimination:

• In adults, the primary route of zinc excretion is through the gastrointestinal tract, with elimination occurring in the feces.

• A smaller proportion of zinc is excreted through the kidneys in urine.

• Preterm infants with very low birth weight exhibit higher urinary zinc excretion rates in the neonatal period, gradually reaching levels comparable to those of normal adults by two months of age.

• Additionally, the body experiences endogenous zinc loss through hair loss, skin desquamation, and sweat.

Toxicity:

• Zinc sulfate injection includes aluminum, which is potentially toxic in prolonged use for individuals with impaired kidney function.

• Inhaling Zinc sulfate might cause nasal and throat irritation.

• Exposure to Zinc sulfate can lead to symptoms such as headache, dizziness, nausea, and vomiting. No specific occupational exposure limits have been set for Zinc sulfate.

• Zinc sulfate irritates the gastrointestinal tract and has historically caused fatalities due to gastrointestinal bleeding from smaller ingestions.

• It irritates the skin and eyes and can induce contact sensitivity.

• While there are no documented reports of Zinc sulfate inhalation, it could irritate the respiratory system.

• Ingesting Zinc sulfate causes gastrointestinal irritation, headache, and dizziness. Fatalities have occurred, albeit less frequently than with Zinc chloride ingestion.

• Chronic excessive ingestion may result in reversible anemia, decreased white blood cell count, transient irritability, tremors, and seizures, particularly in cases involving infants inadvertently given excess Zinc sulfate supplements.

• Excessive Zinc sulfate in parenteral nutrition solutions has been associated with symptoms such as nausea, vomiting, anemia, reduced platelet count, and increased amylase activity.

What Are the Contraindications of Zinc Sulfate Injection?

• There are no established contraindications.

• Excessive zinc accumulation may occur in instances of renal failure.

• Overdosing can result in zinc toxicity.

• Ingesting a zinc supplement of 2 gm/day (gram per day) may cause acute toxicity, presenting symptoms such as nausea, vomiting, abdominal pain, diarrhea, and convulsions.

• Prolonged excessive intake may lead to symptoms like tiredness, anemia, reduced white blood cell count, and disturbances in the central nervous system, primarily due to decreased copper levels.

Warnings and Precautions:

Pulmonary Embolism Due to Pulmonary Vascular Precipitates:

• Pulmonary vascular precipitates leading to embolism and respiratory distress have been observed in individuals receiving parenteral nutrition.

• The cause of precipitate formation is not universally identified, but in fatal instances, pulmonary emboli result from calcium phosphate precipitates.

• Precipitation has occurred post-in-line filtration; in vivo, precipitate formation is also possible.

• If signs of respiratory distress arise, cease parenteral nutrition infusion and initiate medical evaluation. Regularly inspect the solution, infusion set, and catheter for precipitates.

Vein Damage and Thrombosis:

• With its low pH (Potential of Hydrogen), Zinc sulfate injection should be prepared and used as an admixture in parenteral nutrition solutions, not for direct intravenous infusion.

• Consider the osmolarity of the final solution when deciding on peripheral or central administration. Solutions exceeding 900 mOsm/L (milliosmoles/liter) must be administered through a central catheter to avoid vein irritation, damage, or thrombosis.

• Peripheral access complications may include venous thrombophlebitis; remove the catheter promptly if thrombophlebitis occurs.

Aluminum Toxicity:

• Zinc sulfate injection contains potentially toxic aluminum, which is particularly risky for preterm infants due to their immature kidneys and high requirements for aluminum-containing solutions.

• Patients with impaired kidney function, including preterm infants, may accumulate toxic levels of aluminum with prolonged parenteral administration.

• Maintain total daily patient exposure to aluminum from the admixture, including other small-volume parenteral products, at no more than 5 mcg/kg/day (microgram/kilogram/day).

Monitoring and Laboratory Tests:

• Regularly monitor zinc concentrations, fluid and electrolyte status, serum osmolarity, blood glucose, liver and kidney function, blood count, and coagulation parameters throughout treatment.

Copper Deficiency:

• High doses of supplemental zinc may lead to decreased enteral copper absorption and copper deficiency.

• Complications of copper deficiency include anemia, leukopenia, thrombocytopenia, myeloneuropathy, and nephrotic-range proteinuria.

• Interrupt zinc treatment and assess zinc, copper, and ceruloplasmin levels if signs of copper deficiency arise. Treat with supplemental copper and discontinue zinc supplementation.

Hypersensitivity Reactions:

• Hypersensitivity reactions, identified in post-marketing reports, can occur with subcutaneously administered zinc-containing insulin products.

• Reactions may include injection site induration, erythema, pruritus, papular rash, generalized urticaria, facial swelling, and dyspnea.

• Discontinue Zinc sulfate injection and initiate appropriate medical treatment if hypersensitivity reactions occur.

What Are the Drug Interactions of Zinc Sulfate Injection?

• Medications can interact with this product, impacting their effectiveness or increasing the risk of side effects.

• Avoid changing any medication without the doctor's approval.

• Potential interactions exist with drugs like Penicillamine and those containing phosphorus.

• Zinc sulfate products might decrease the absorption of tetracycline antibiotics, bisphosphonates, and quinolone antibiotics.

• It is advised to separate the doses of these medications from Zinc sulfate as much as possible.

• Seek guidance from a doctor or pharmacist to determine the waiting duration between doses and to create a dosing schedule that aligns with all medications.

Specific Considerations:

Pregnancy:

• Administering the recommended dose of Zinc sulfate injection in parenteral nutrition does not pose significant risks for major birth defects or miscarriage.

• Zinc deficiency links to adverse pregnancy outcomes. Pregnant women with increased trace element demand may opt for parenteral nutrition if oral or enteral intake is insufficient.

Lactation:

• Administering the recommended dose of Zinc sulfate injection in parenteral nutrition does not harm breastfed infants. Consider the benefits of breastfeeding against potential adverse effects.

Pediatric Use:

• Zinc sulfate injection is approved for pediatric use, including neonates, when oral or enteral nutrition is not feasible.

• Preterm infants on prolonged parenteral nutrition may have an increased risk of aluminum toxicity.

Geriatric Use:

• Clinical experience shows no difference in zinc requirements between elderly and younger patients.

• Dose selection should be individualized based on the patient's clinical condition and nutritional needs.