NAD

Nicotinamide adenine dinucleotide (NAD+) is an endogenous coenzyme present in all living cells. It is a bulk drug substance with no FDA-approved drug product, and no FDA-labeled indication or dose exists for any route. NAD+ is compounded into injectable and topical preparations pursuant to patient-specific prescriptions.

No FDA-labeled indication exists. Prescribers use compounded NAD+ by intravenous, intramuscular, subcutaneous and topical routes at their discretion.

NAD+ and its reduced form NADH carry electrons in glycolysis, the citric acid cycle and oxidative phosphorylation. NAD+ is also a substrate for sirtuins, poly(ADP-ribose) polymerases and CD38, enzymes involved in DNA repair, gene regulation and cell signaling. Tissue NAD+ levels decline with age and some disease states; whether exogenously administered NAD+ raises intracellular NAD+ in humans has not been established.

Human pharmacokinetic data are limited. Extracellular NAD+ does not readily cross cell membranes and is rapidly broken down by ectoenzymes such as CD38 and CD73 to nicotinamide mononucleotide, nicotinamide riboside, nicotinamide and adenosine, which cells can take up and use to resynthesize NAD+. Nicotinamide is metabolized in the liver and excreted in urine. Topical absorption has not been characterized.

• Hypersensitivity to NAD+ or any component of the preparation. No other contraindications are established.

• Intravenous use: infusion-related reactions, including flushing, chest tightness, dyspnea, nausea, abdominal cramping, headache and anxiety, are common and are generally related to infusion rate; administer under clinical supervision.
• Intramuscular and subcutaneous use: injection-site pain, erythema and swelling.
• Safety data in pregnancy, lactation, children, and hepatic or renal impairment are not available.
• Topical use: avoid broken skin, eyes and mucous membranes.

No clinically established drug interactions are known. Concurrent niacin, nicotinamide, nicotinamide riboside or other NAD+ precursor supplements add to total nicotinamide exposure.

Intravenous: flushing, chest pressure, shortness of breath, nausea, abdominal cramping, headache, lightheadedness and fatigue during or after infusion. Injection: local pain, redness, swelling and bruising. Topical: local irritation or itching.

No human data exist on exogenous NAD+ in pregnancy or lactation. Use is not recommended unless the prescriber judges it necessary; this is a precaution, not a labeled contraindication.

Intravenous use: vital signs and symptoms during infusion, with rate adjustment as needed. All routes: injection-site or skin reactions and any hypersensitivity.

• The Merck Index: nicotinamide adenine dinucleotide.
• USP General Chapter <797> Pharmaceutical Compounding: Sterile Preparations.
• USP General Chapter <795> Pharmaceutical Compounding: Nonsterile Preparations.