Zinc Sulfate

Introduction Overview

Generic Name

zinc sulfate

Brand Name

Orazinc 110, Orazinc 220, Zinc, Zinc-220, Zinca-pak, Mar-Zinc, Verazinc, Zincate, Zinc CR, Micro-Zn, Zinc 50 mg Pink

Dosage Form

oral capsule, oral tablet, injectable solution

Drug Class

Minerals and electrolytes

Pharmacokinetics

Absorption:
Zinc sulfate is absorbed primarily in the small intestine through a carrier-mediated process involving zinc transporters such as ZIP4 (SLC39A4). Absorption efficiency depends on the zinc status of the individual; deficiency enhances absorption while excess zinc intake suppresses uptake. Dietary components influence absorption significantly—phytates found in whole grains and legumes bind zinc reducing its bioavailability, whereas animal proteins may enhance absorption. Oral zinc sulfate formulations are typically administered with food to mitigate gastrointestinal intolerance, though this may slightly reduce the absorption rate. Research has demonstrated that zinc sulfate exhibits moderate bioavailability compared to other zinc salts, with absorption values ranging from approximately 20-40% in healthy adults.

Distribution:
Once absorbed, zinc is transported in plasma bound primarily to albumin and alpha-2-macroglobulin. Distribution is widespread, with high concentrations found in skeletal muscle, bone, liver, kidney, and skin. Zinc does not accumulate excessively in tissues but exists in a dynamic equilibrium influenced by metallothionein and other zinc-binding proteins that regulate intracellular zinc levels. In the body, zinc functions as a catalytic, structural, and regulatory ion essential for hundreds of enzymatic reactions. The plasma half-life of zinc is short, reflecting rapid cellular uptake and incorporation into physiological processes. Distribution to the central nervous system occurs via uptake across the blood-brain barrier, playing a role in neurophysiology.

Metabolism:
Zinc is an essential trace element and not metabolized per se but is involved as a cofactor in numerous enzymatic systems including DNA and RNA polymerases, carbonic anhydrase, and superoxide dismutase. Zinc homeostasis is maintained by balancing absorption with excretion. Intracellular zinc levels are tightly controlled via metallothionein binding and zinc transporter proteins, which modulate cellular uptake, sequestration, and efflux. Zinc sulfate administration supplements systemic zinc pools, impacting cellular metabolic pathways including antioxidant defenses and protein synthesis.

Elimination:
Excretion of zinc occurs primarily via the gastrointestinal tract through pancreatic and biliary secretions, as well as via sloughed intestinal mucosal cells, making fecal excretion the dominant elimination pathway. Smaller amounts are excreted in urine and sweat. Zinc retention improves in deficiency states to conserve body stores. The half-life of absorbed zinc is influenced by physiologic and pathological states; elevated GI losses can occur in conditions such as burns or chronic diarrhea. Zinc sulfate injections provide zinc intravenously, bypassing absorption processes with renal and fecal elimination predominating depending on clinical context.

Dosage Forms

Available Dosage Forms:
- Oral capsule: 220 mg (equivalent to elemental zinc 50 mg)
- Oral tablet: 110 mg (equivalent to elemental zinc 25 mg)
- Oral tablet: 66 mg (equivalent to elemental zinc 15 mg)
- Injectable formulation: Zinc sulfate injection for intravenous administration

Dosages for Adults and Adolescents:
- Dietary supplementation recommended daily allowance (RDA) for males 19 years and older: 11 mg elemental zinc (upper intake limit 34 mg)
- Dietary supplementation RDA for females 19 years and older: 9 mg elemental zinc (upper intake limit 34 mg)
- Pregnancy: 11 mg elemental zinc (upper intake limit 40 mg)
- Lactation: 12 mg elemental zinc (upper intake limit 40 mg)
- For metabolically stable adults receiving parenteral nutrition (TPN): IV doses of 2.5 to 4 mg elemental zinc daily
- In acute catabolic states on TPN, additional 2 mg elemental zinc per day is recommended
- Patients with small bowel fluid loss require additional supplementation approximately 12.2 mg zinc per liter of small bowel fluid lost

Specific Patient Populations:
- Pediatric dosing varies substantially by age with RDA ranging from 2 mg/day elemental zinc for infants 0-6 months to 11 mg/day for males aged 14-18 years
- Zinc sulfate injection doses for pediatric patients:
* Full-term infants and children up to 5 years: 100 mcg/kg/day elemental zinc
* Premature infants (<1500 g): 300 mcg/kg/day elemental zinc
- Pregnant and lactating women require increased zinc to support fetal growth and milk production, necessitating dose adjustments within recommended upper limits
- Patients with gastrointestinal losses or malabsorption syndromes require tailored dosing to compensate for zinc depletion
- Caution advised in patients with known hypersensitivity to zinc or zinc salts.

Mechanism Of Action

Zinc sulfate acts primarily as a source of elemental zinc, an essential trace mineral that functions as a catalytic and structural cofactor in numerous enzymes and transcription factors pivotal to cellular metabolism and DNA synthesis. At the molecular level, zinc binds to specific sites on metalloproteins and enzymes, stabilizing their structures and maintaining functional conformations necessary for biological activity.

Cellularly, zinc modulates various signaling pathways including those involved in immune function, such as the activation and proliferation of T-lymphocytes, and the regulation of cytokine production. Zinc ions influence oxidative stress responses by contributing to the function of antioxidant enzymes like superoxide dismutase, reducing cellular damage.

Biochemically, zinc participates in the regulation of gene expression through zinc-finger transcription factors which control the expression of genes involved in growth, differentiation, and repair. Clinical implications of zinc’s mechanism include its role in wound healing, immune defense, growth and development, and sensory function.

Comparatively, zinc sulfate provides a bioavailable form of zinc among various salts, differing from zinc acetate or zinc gluconate in absorption kinetics but sharing the fundamental mechanism of zinc ion supplementation. Clinical studies have demonstrated zinc sulfate’s efficacy in correcting zinc deficiency states, supporting immune function, and improving clinical outcomes in conditions such as zinc-responsive dermatitis and taste disorders.

Pharmacological Actions

Provides essential zinc, a vital trace element involved in numerous enzymatic reactions
Supports immune system function by enhancing T-cell-mediated immunity and cytokine regulation
Acts as an antioxidant cofactor through enzymes such as superoxide dismutase, reducing free radical damage
Facilitates wound healing by promoting cell proliferation and collagen synthesis
Maintains structural integrity of proteins and cellular membranes via zinc-finger protein stabilization
Contributes to DNA and RNA synthesis necessary for cellular division and repair
Regulates sensory functions including taste and smell by influencing neural signaling pathways
Inhibits apoptosis and modulates inflammatory responses at the cellular level
Stimulates growth and development by supporting metabolic pathways
Balances cellular redox status and promotes enzymatic activities in metabolic processes
Enhances gastrointestinal mucosal defenses and repair mechanisms
Metallothionein induction protects against heavy metal toxicity and oxidative stress

Therapeutic Or Clinical Uses

Treatment and prevention of zinc deficiency states in adults and children
Dietary supplementation to maintain adequate zinc status in populations at risk
Adjunctive therapy in patients receiving long-term total parenteral nutrition (TPN) requiring zinc supplementation
Management of conditions related to impaired wound healing and tissue repair
Supportive treatment in immune dysfunction and recurrent infections
Used in certain dermatological conditions like acrodermatitis enteropathica and zinc-responsive dermatitis
Prevention of growth retardation and delayed development associated with zinc deficiency
Supportive treatment in taste and smell disorders associated with zinc deficiency
Beneficial in chronic gastrointestinal losses due to diarrhea or surgeries resulting in malabsorption
Adjunctive therapy during pregnancy and lactation to meet increased zinc demands
Potential use in managing certain inflammatory and oxidative stress-related disorders
May be employed off-label in the supportive care of upper respiratory tract infections and the common cold

Side Or Adverse Effects

Nausea and gastrointestinal upset such as abdominal pain or discomfort
Vomiting, especially with doses taken on an empty stomach
Metallic taste sensation which may affect compliance
Possible allergic reactions including rash, pruritus, or urticaria
Risk of copper deficiency and related hematological abnormalities with chronic high-dose use
Interference with absorption of other trace minerals such as iron and copper leading to mineral imbalance
Gastrointestinal irritation and rarely gastric ulceration with prolonged use
Headache and dizziness reported infrequently
Potential for zinc toxicity presenting as lethargy, ataxia, and immune dysfunction with overdose
Possible changes in lipid profile with long-term, high-dose zinc administration
Rare cases of hypersensitivity pneumonitis in occupational or high exposure scenarios
May exacerbate pre-existing anemia if copper deficiency develops

Precautions

Use cautiously in patients with pre-existing copper deficiency or at risk for mineral imbalances
Administer with food to minimize gastrointestinal irritation and prevent nausea
Avoid concomitant administration with high-calcium or high-phosphorus foods as these reduce zinc absorption
Monitor zinc levels in patients on long-term supplementation or those receiving parenteral nutrition
Evaluate for signs of allergic reactions or hypersensitivity especially upon initial dosing
Adjust doses appropriately in pediatric, pregnant, and lactating patients according to recommended guidelines
Use with caution in patients with renal impairment given altered zinc elimination
Advise patients to adhere to recommended dosing to prevent toxicity
Counsel on potential interactions with other minerals and medications that may affect zinc status
Avoid use in patients with known hypersensitivity to zinc sulfate or its preservatives
Be vigilant for signs of gastrointestinal bleeding during prolonged use
Careful consideration when prescribing to patients with a history of gastrointestinal ulcers or bleeding disorders

Warnings

Follow dosing instructions strictly to avoid zinc overdose, which can be toxic
Keep out of reach of children to prevent accidental ingestion and toxicity
Discontinue use and seek emergency medical attention if signs of allergic reaction occur (hives, swelling, difficulty breathing)
Avoid concurrent use with products containing high calcium or phosphorus to prevent decreased zinc absorption
Pregnant and lactating women should use under medical supervision to avoid excessive zinc intake
Zinc sulfate may interact with medications and supplements; inform healthcare providers about all concomitant products
Overdosage may cause severe nausea, vomiting, dehydration, and restlessness requiring prompt medical intervention
Do not use zinc sulfate for indications other than those prescribed
Avoid use in patients with known hypersensitivity to zinc sulfate
Monitor patients on long-term therapy for potential mineral imbalances
Use caution in manufacturing settings due to potential inhalation hazards from powder forms
In patients receiving parenteral nutrition, correct dosing is essential to avoid systemic zinc deficiency or toxicity

Contraindication

Known hypersensitivity or allergy to zinc sulfate or any components of the formulation
Patients with documented copper deficiency anemia without concurrent copper supplementation
Severe renal impairment where zinc excretion is significantly compromised unless monitored
Use in patients with active peptic ulcer disease may be contraindicated due to potential GI irritation
Avoid use in individuals with iron overload disorders without medical supervision
Not indicated for use in prophylaxis without clinical evidence of deficiency
Contraindicated in patients with history of zinc toxicity
Avoid use in neonates without specific indications and monitoring
Patients with severe allergic reactions to previous mineral supplements
Avoid concurrent administration with chelating agents unless separated by appropriate time intervals

Drug Interactions

Absorption reduced by concurrent intake of high-calcium foods and supplements (e.g., milk, dairy products)
Phosphorus-containing foods and beverages (e.g., cola drinks) can impair zinc bioavailability
May reduce absorption of tetracycline and quinolone antibiotics; separate dosing by at least 2 hours
Concurrent administration with penicillamine reduces zinc absorption and effectiveness
High doses of zinc may interfere with copper absorption leading to copper deficiency
May interact with diuretics affecting zinc excretion and plasma levels
Antibiotics such as cephalexin may have altered serum concentrations when taken with zinc sulfate
Zinc can affect the efficacy of certain antivirals when co-administered
Concurrent use with iron supplements may reduce absorption of both minerals if taken simultaneously
Potential interaction with chemotherapeutic agents altering drug toxicity and efficacy profile
Co-administration with folic acid may influence zinc metabolism
Herbal products containing high levels of minerals should be monitored during zinc therapy
Interactions with antacids containing magnesium or aluminum hydroxide reducing zinc absorption
Zinc supplements may modulate immune responses affecting immunosuppressant drugs
Alteration of absorption kinetics of oral contraceptives with concomitant zinc supplementation

Preparations Of The Drug

Oral capsules containing 220 mg zinc sulfate equivalent to 50 mg elemental zinc
Oral tablets available in 110 mg (25 mg elemental zinc) and 66 mg (15 mg elemental zinc) strengths
Injectable zinc sulfate formulation for intravenous administration in critical care and TPN settings
Commercially available brand formulations: Orazinc 110, Orazinc 220, Zinc-220, Zinca-pak, Micro-Zn, Zincate, Zinc CR
Powdered forms intended for reconstitution in clinical settings
Combination products containing zinc sulfate with other minerals or vitamins for dietary supplementation
Topical preparations containing zinc sulfate for dermatological uses (less common)
Various generic and brand-name oral supplements regulated as dietary minerals
Pharmaceutical-grade intravenous zinc sulfate indicated for parenteral nutrition supplementation
Liquid oral preparations formulated for pediatric dose adjustments
Extended release formulations designed for sustained zinc delivery
Effervescent tablets enhancing palatability and absorption
Over-the-counter zinc sulfate supplements commonly used for prevention of deficiency
Pharmaceutical packaging includes bottles, blister packs, and parenteral vials
Storage conditions generally involve room temperature protection from moisture and heat