18.2 Parenteral, TPN & Cytotoxic Preparation

Parenteral preparations are administered by a route that bypasses gastrointestinal and skin barriers, so compatibility and sterility are equally critical. The DHA Pharmacist blueprint tests two distinct knowledge sets here: (1) the physicochemical compatibility of parenteral nutrition components, especially calcium-phosphate interactions, and (2) the containment requirements for hazardous and cytotoxic drugs under USP <800>.

Parenteral Nutrition Components

A total parenteral nutrition (TPN) formulation typically contains:

• Amino acids — the nitrogen source
• Dextrose — the carbohydrate/energy source
• Lipids (intravenous fat emulsion) — calorie source and essential fatty acids
• Electrolytes — sodium, potassium, magnesium, calcium, phosphate, chloride, acetate
• Trace elements — zinc, copper, chromium, manganese, selenium
• Vitamins — multivitamin preparation; some components (e.g., riboflavin, vitamin A) are light-sensitive

A 2-in-1 admixture contains dextrose and amino acids only; lipids are infused separately via a Y-site. A 3-in-1 (total nutrient admixture, TNA) combines dextrose, amino acids, and lipids in a single bag. The 3-in-1 is convenient and reduces line-handling, but lipids can destabilize the emulsion and shorten the permissible hang time.

Calcium-Phosphate Precipitation

The single most tested parenteral incompatibility is calcium-phosphate precipitation. When calcium and phosphate ions exceed their solubility product in the TPN, insoluble calcium phosphate crystals form and can embolize to pulmonary capillaries.

Key factors that affect calcium-phosphate solubility:

Exam trap: Calcium gluconate, not calcium chloride, is the preferred salt for neonatal and adult TPN because it produces a lower localized calcium concentration at the injection site and a lower precipitation risk. The traditional rule of "phosphate first, calcium last" is a sequence safeguard, not a substitute for calculating the Ca/Ph product against published solubility curves.

Incompatibilities — General Principles

Beyond calcium-phosphate, parenteral incompatibilities fall into physicochemical categories:

• Precipitation — visible or invisible solid formation (e.g., calcium phosphate, ceftriaxone-calcium).
• pH-mediated incompatibility — many drugs are soluble only at a narrow pH range; mixing an acidic and an alkaline drug can precipitate one of them.
• Ionic incompatibility — oppositely charged drugs or ions form insoluble complexes.
• Adsorption — drug binds to infusion-set materials (e.g., nitroglycerin to PVC).
• Light degradation — photolabile drugs (some vitamins, amphotericin B) require light protection.

Hang Time and Stability

TPN hang time is generally limited to 24 hours once the infusion begins, because lipid-containing admixtures can support microbial growth and because emulsion stability degrades over time. For 3-in-1 admixtures, some institutions shorten hang time further. Lipids infused alone (as in 2-in-1 setups) typically have a 12-hour hang limit because the emulsion is a growth medium.

Some vitamins (notably vitamin A and riboflavin) degrade on light exposure, so TPN bags may be protected from light during storage and infusion when stability data require it.

Cytotoxic and Hazardous Drug Preparation — USP <800>

USP <800> governs handling of hazardous drugs (HDs) — antineoplastics, some hormones, certain antivirals, and other agents identified by the National Institute for Occupational Safety and Health (NIOSH). The chapter applies to the entire HD lifecycle: receipt, storage, compounding, dispensing, administration, and disposal.

Engineering and PPE requirements for HD sterile compounding:

Why a Class II B2? A Class II B2 BSC recirculates no air to the operator — 100% of the contaminated airflow is exhausted through HEPA filtration to the outside. This protects both the product (from the operator's microbial shed) and the operator (from hazardous drug aerosols and vapors). A Class II A2 recirculates a portion of air and is not preferred for high-risk cytotoxic work.

Closed-system transfer devices (CSTDs) mechanically prevent drug aerosol and vapor from escaping during reconstitution, transfer, and administration. USP <800> requires CSTDs for administration and recommends them for compounding; they are a key exam concept for HD handling.

Exam trap: Hazardous drug compounding must never occur in a horizontal LAFW. The horizontal airflow would direct hazardous aerosols toward the operator's face. Use a containment PEC (BSC or CACI) under negative pressure, separate from the non-hazardous compounding area.

Administration-Side Considerations

Cytotoxic administration also requires PPE: double chemo gloves, impervious gown, eye protection, and a CSTD on the IV line. Spills are managed with a designated HD spill kit (absorbent pads, spill control pillows, chemo-rated gloves, gown, face shield, scoop, and hazardous-waste bag). Contaminated PPE and disposable materials are disposed of as trace chemotherapy waste, typically in yellow or blue chemo-rated containers.