Spinal Anaesthesia Tray

Dextrose:

• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• Directions for use of pharmacy bulk package container
• How supplied
• Spinal Anaesthesia Tray (Dextrose) reviews

INDICATIONS AND USAGE

70% Spinal Anaesthesia Tray (Dextrose) Injection USP is indicated as a caloric component in a parenteral nutrition regimen. 70% Spinal Anaesthesia Tray (Dextrose) Injection USP is used with an appropriate protein (nitrogen) source in the prevention of nitrogen loss or in the treatment of negative nitrogen balance in patients where: (1) the alimentary tract cannot or should not be used, (2) gastrointestinal absorption of protein is impaired, or (3) metabolic requirements for protein are substantially increased, as with extensive burns.

CONTRAINDICATIONS

The infusion of 70% Spinal Anaesthesia Tray (Dextrose) Injection USP is contraindicated in patients having intracranial or intraspinal hemorrhage, in patients who are severely dehydrated, in patients who are anuric, and in patients in hepatic coma.

Solutions containing Spinal Anaesthesia Tray (Dextrose) may be contraindicated in patients with hypersensitivity to corn products.

WARNINGS

This injection is for compounding only, not for direct infusion.

Dilute before use to a concentration which will, when administered with an amino acid (nitrogen) source, result in an appropriate calorie to gram of nitrogen ratio and which has an osmolarity consistent with the route of administration.

Unless appropriately diluted, the infusion of hypertonic Spinal Anaesthesia Tray (Dextrose) injection into a peripheral vein may result in vein irritation, vein damage, and thrombosis. Strongly hypertonic nutrient solutions should only be administered through an indwelling intravenous catheter with the tip located in a large central vein such as the superior vena cava.

Use of 70% Spinal Anaesthesia Tray (Dextrose) Injection USP to prepare parenteral nutritional admixtures may be incompatible with other components, especially calcium and phosphate salts and lipid emulsions. Incompatibility of admixed components can produce precipitates which may cause particulate emboli. Use 70% Spinal Anaesthesia Tray (Dextrose) Injection USP only to prepare formulations that are known to be stable: refer to standard texts for further information.

The administration of intravenous solutions can cause fluid and/or solute overload resulting in dilution of serum electrolyte concentrations, overhydration, congested states or pulmonary edema. The risk of dilutional states is inversely proportional to the electrolyte concentration.

WARNING: 70% Spinal Anaesthesia Tray (Dextrose) Injection USP contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.

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

Prolonged infusion of isotonic or hypotonic Spinal Anaesthesia Tray (Dextrose) in water may increase the volume of extracellular fluid and cause water intoxication.

Solutions containing Spinal Anaesthesia Tray (Dextrose) without electrolytes should not be administered simultaneously with blood through the same infusion set because of the possibility of agglomeration.

Excessive administration of potassium-free Spinal Anaesthesia Tray (Dextrose) solutions may result in significant hypokalemia. Serum potassium levels should be maintained and potassium supplemented as required.

In very low birth weight infants, excessive or rapid administration of Spinal Anaesthesia Tray (Dextrose) injection may result in increased serum osmolality and possible intracerebral hemorrhage.

PRECAUTIONS

General

This solution should be used with care in patients with hypervolemia, renal insufficiency, urinary tract obstruction, or impending or frank cardiac decompensation.

Solutions containing Spinal Anaesthesia Tray should be used with caution in patients with overt or known subclinical diabetes mellitus or carbohydrate intolerance for any reason.

Essential electrolytes, minerals, and vitamins should be supplied as needed.

Hypokalemia may develop during parenteral administration of hypertonic Spinal Anaesthesia Tray (Dextrose) solutions. Sufficient amounts of potassium should be added to Spinal Anaesthesia Tray (Dextrose) solutions administered to fasting patients with good renal function, especially those on digitalis therapy.

To minimize the risk of possible incompatibilities arising from mixing this solution with other additives that may be prescribed, the final infusate should be inspected for cloudiness or precipitation immediately after mixing, prior to administration, and periodically during administration. See WARNINGS .

Do not use plastic container in series connection.

If administration of 70% Spinal Anaesthesia Tray (Dextrose) Injection USP after admixture or dilution is controlled by a pumping device, care must be taken to discontinue pumping action before the container runs dry or air embolism may result. If administration is not controlled by a pumping device, refrain from applying excessive pressure (>300mmHg) causing distortion to the container such as wringing or twisting. Such handling could result in breakage of the container.

This solution is intended for intravenous administration after admixture or dilution using sterile equipment. When using an automated compounding device replace all disposable components as recommended by manufacturer and at least every 24 hours.

Aseptic technique is essential with the use of sterile preparations for compounding nutritional admixtures. Discard container within 4 hours of entering closure.

Administration of hypertonic Spinal Anaesthesia Tray (Dextrose) and amino acid solutions via central venous catheter may be associated with complications which can be prevented or minimized by careful attention to all aspects of the procedure. This includes attention to solution preparation, administration and patient monitoring.

It is essential that a carefully prepared protocol, based upon current medical practice, be followed, preferably by an experienced team. The package insert of the protein (nitrogen) source should be consulted for dosage and all precautionary information.

Use only if solution is clear and container and seals are intact.

70% Spinal Anaesthesia Tray (Dextrose) Injection USP contains no more than 25 µg/L of aluminum.

Laboratory Tests

Clinical evaluation and periodic laboratory determinations are necessary to monitor changes in fluid balance, electrolyte concentrations, and acid-base balance during prolonged parenteral therapy or whenever the condition of the patient warrants such evaluation. Significant deviations from normal concentrations may require tailoring of the electrolyte pattern, in these or alternative solutions.

Drug Interactions

Caution must be exercised in the administration of 70% Spinal Anaesthesia Tray Injection USP to patients receiving corticosteroids or corticotropin. Some additives may be incompatible. Consult with pharmacist. When introducing additives, use aseptic techniques. Mix thoroughly. Do not store. Dispose of any unused product. See WARNINGS .

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies with Spinal Anaesthesia Tray (Dextrose) Injections USP have not been performed to evaluate carcinogenic potential, mutagenic potential or effects on fertility.

Pregnancy

Pregnancy Category C

There are no adequate and well controlled studies with Spinal Anaesthesia Tray Injections, USP in pregnant women and animal reproduction studies have not been conducted with this drug. Therefore, it is not known whether Spinal Anaesthesia Tray (Dextrose) Injections USP can cause fetal harm when administered to a pregnant woman. Spinal Anaesthesia Tray (Dextrose) Injections USP should be given during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor and Delivery

Intrapartum maternal intravenous infusion of glucose-containing solutions may produce maternal hyperglycemia with subsequent fetal hyperglycemia and fetal metabolic acidosis. Fetal hyperglycemia can result in increased fetal insulin levels which may result in neonatal hypoglycemia following delivery. Consider the potential risks and benefits for each specific patient before administering Spinal Anaesthesia Tray (Dextrose) Injection, USP.

Nursing Mothers

It is not known if this drug is present in human milk. Because many drugs are present in human milk, caution should be exercised when Spinal Anaesthesia Tray Injections USP are administered to a nursing woman.

Pediatric Use

The use of Spinal Anaesthesia Tray (Dextrose) in pediatric patients is based on clinical practice (see DOSAGE AND ADMINISTRATION ). Because of their hypertonicity, 70% Spinal Anaesthesia Tray (Dextrose) Injections must be diluted prior to administration.

Newborns – especially those born premature and with low birth weight - are at increased risk of developing hypo- or hyperglycemia and therefore need close monitoring during treatment with intravenous glucose solutions to ensure adequate glycemic control in order to avoid potential long term adverse effects. Hypoglycemia in the newborn can cause prolonged seizures, coma and brain damage. Hyperglycemia has been associated with intraventricular hemorrhage, late onset bacterial and fungal infection, retinopathy of prematurity, necrotizing enterocolitis, bronchopulmonary dysplasia, prolonged length of hospital stay, and death.

Geriatric Use

An evaluation of literature revealed no clinical experience identifying differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

See WARNINGS .

ADVERSE REACTIONS

Reactions which may occur because of the solution or the technique of administration include febrile response, infection at the site of injection, venous thrombosis or phlebitis extending from the site of injection, extravasation and hypervolemia. Incompatibility of admixed components can produce precipitates which may cause particulate emboli.

Hyperosmolar syndrome, resulting from excessively rapid administration of concentrated Spinal Anaesthesia Tray (Dextrose) may cause hypovolemia, dehydration, mental confusion and/or loss of consciousness. Too rapid infusion of hypertonic solutions may cause local pain and venous irritation. Rate of administration should be adjusted according to tolerance. Use of the largest peripheral vein and a small bore needle is recommended. (See DOSAGE AND ADMINISTRATION .)

Hypersensitivity reactions, including anaphylaxis and chills.

If an adverse reaction does occur, discontinue the infusion, evaluate the patient, institute appropriate therapeutic countermeasures, and save the remainder of the fluid for examination if deemed necessary.

OVERDOSAGE

In the event of a fluid or solute overload during parenteral therapy, reevaluate the patient’s condition and institute appropriate corrective treatment.

DOSAGE AND ADMINISTRATION

This solution is for intravenous use only after admixture or dilution.

70% Spinal Anaesthesia Tray Injection USP is designed for use with automated compounding devices for preparing intravenous nutritional admixtures or for the filling of empty sterile syringes. Dosages will be in accordance with the recommendation of the prescribing physician. 70% Spinal Anaesthesia Tray (Dextrose) Injection USP is not intended for direct infusion. Admixtures should be made by, or under the direction of, a pharmacist using strict aseptic technique under a laminar flow hood. Compounded admixtures may be stored under refrigeration for up to 24 hours. Administration of admixtures should be completed within 24 hours after removal from refrigeration.

Dosage is to be directed by a physician and is dependent upon age, weight, clinical condition of the patient and laboratory determinations. Frequent laboratory determinations and clinical evaluation are essential to monitor changes in blood glucose and electrolyte concentrations, and fluid and electrolyte balance during prolonged parenteral therapy.

Fluid administration should be based on calculated maintenance or replacement fluid requirements for each patient.

Pediatric Use

The dosage selection and constant infusion rate of intravenous Spinal Anaesthesia Tray (Dextrose) must be selected with caution in pediatric patients, particularly neonates and low birth weight infants, because of the increased risk of hyperglycemia/hypoglycemia. Frequent monitoring of serum glucose concentrations is required when Spinal Anaesthesia Tray (Dextrose) is prescribed to pediatric patients, particularly neonates and low birth weight infants. The infusion rate and volume depends on the age, weight, clinical and metabolic conditions of the patient, concomitant therapy and should be determined by the consulting physician experienced in pediatric intravenous fluid therapy.

Directions for Use of Pharmacy Bulk Package Container

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration or admixture and final infusate should be inspected for cloudiness or precipitation immediately after mixing, prior to administration, and periodically during administration, whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions where possible.

70% Spinal Anaesthesia Tray (Dextrose) Injection USP in the Pharmacy Bulk Package is intended for use in the preparation of sterile, intravenous admixtures.

Refer to standard texts and guidelines on the preparation of parenteral nutritional admixtures.

When compounding admixtures, use aseptic technique. Mix thoroughly.

Do not store any unused portion of 70% Spinal Anaesthesia Tray (Dextrose) Injection USP.

TO OPEN:

• Inspect overwrap. Do not use if overwrap has been damaged.
• Do not use unless solution is clear and closure is intact.
• Tear overwrap starting from the tear notches. (Figure 1)
  

• Inspect the container for minute leaks by squeezing inner bag firmly. If leaks are found, discard the bag as sterility may be impaired.
• For compounding only. Do not use for direct infusion
  

  PREPARATION FOR ADMIXING
  

  Note: Important Admixing Information
  

  
  

• The Pharmacy Bulk Package is to be used only in a suitable work area such as a laminar air flow hood (or an equivalent clean air compounding area).
• The contents are restricted to the preparation of admixtures for infusion or, through a sterile transfer device, for the filling of empty sterile syringes.
• Additives may be incompatible with the fluid withdrawn from this container. When compounding admixtures, use aseptic technique, mix thoroughly and do not store.
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution container permits. (see PRECAUTIONS, General )

• Do not use/penetrate blocked port.
  

• Remove aluminum foil of set port at the bottom of container.
• Attach suitable transfer device or compounding set (Figure 2). Refer to complete directions accompanying device.
• Hang bag on suitable fixture (Figure 3).
• Once container closure has been penetrated, withdrawal of content should be completed within 4 hours.

HOW SUPPLIED

70% Spinal Anaesthesia Tray (Dextrose) Injection USP is supplied in 2000 mL Pharmacy Bulk Package containers packaged 4 per case.

NDC REF SIZE

0264-7387-50 S8705 2000 mL

Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. Protect from freezing. It is recommended that the product be stored at room temperature (25°C); however, brief exposure up to 40°C does not adversely affect the product.

Rx only

Initiated: February 2015

B. Braun Medical Inc.

Bethlehem, PA 18018-3524 USA

1-800-227-2862

www.bbraun.com

Y36-002-865 LD-355-2

Epinephrine:

• Spinal Anaesthesia Tray (Epinephrine) reviews

Indication: Used to treat anaphylaxis and sepsis. Also one of the body's main adrenergic neurotransmitters.

Spinal Anaesthesia Tray (Epinephrine) is indicated for intravenous injection in treatment of acute hypersensitivity, treatment of acute asthmatic attacks to relieve bronchospasm, and treatment and prophylaxis of cardiac arrest and attacks of transitory atrioventricular heart block with syncopal seizures (Stokes-Adams Syndrome). The actions of Spinal Anaesthesia Tray (Epinephrine) resemble the effects of stimulation of adrenergic nerves. To a variable degree it acts on both alpha and beta receptor sites of sympathetic effector cells. Its most prominent actions are on the beta receptors of the heart, vascular and other smooth muscle. When given by rapid intravenous injection, it produces a rapid rise in blood pressure, mainly systolic, by (1) direct stimulation of cardiac muscle which increases the strength of ventricular contraction, (2) increasing the heart rate and (3) constriction of the arterioles in the skin, mucosa and splanchnic areas of the circulation. When given by slow intravenous injection, Spinal Anaesthesia Tray (Epinephrine) usually produces only a moderate rise in systolic and a fall in diastolic pressure. Although some increase in pulse pressure occurs, there is usually no great elevation in mean blood pressure. Accordingly, the compensatory reflex mechanisms that come into play with a pronounced increase in blood pressure do not antagonize the direct cardiac actions of Spinal Anaesthesia Tray (Epinephrine) as much as with catecholamines that have a predominant action on alpha receptors.

Lidocaine Hydrochloride:

• Pharmacological action
• Pharmacokinetics
• Why is Spinal Anaesthesia Tray prescribed?
• Dosage and administration
• Spinal Anaesthesia Tray (Lidocaine Hydrochloride) side effects, adverse reactions
• Spinal Anaesthesia Tray contraindications
• Using during pregnancy and breastfeeding
• Special instructions
• Spinal Anaesthesia Tray drug interactions
• Spinal Anaesthesia Tray in case of emergency / overdose
• Spinal Anaesthesia Tray (Lidocaine Hydrochloride) reviews

Pharmacological action

Spinal Anaesthesia Tray is an antiarrhythmic agent of class IB, local anesthetic, a derivative of acetanilide. This medication has membrane stabilizing activity. Spinal Anaesthesia Tray (Lidocaine Hydrochloride) causes a blockade of sodium channels of excitable membranes of neurons and the membrane of cardiomyocytes.

This drug reduces the duration of the action potential and effective refractory period in Purkinje fibers, inhibits their automaticity. In this case, Spinal Anaesthesia Tray (Lidocaine Hydrochloride) inhibits electrical activity in depolarized, arrhythmogenic sites, but minimally affects the electrical activity of normal tissues. When used in the medium therapeutic doses virtually no effect on myocardial contractility and slows AV-conduction. When applied as an antiarrhythmic agent in IV injection it begin to act in 45-90 seconds, the duration of action is 10-20 minutes; for IM administration the onset of action is in 5-15 minutes, the duration - 60-90 minutes.

Spinal Anaesthesia Tray (Lidocaine Hydrochloride) causes all kinds of local anesthesia: a terminal, infiltration and wires.

Pharmacokinetics

After IM administration absorption of Spinal Anaesthesia Tray (Lidocaine Hydrochloride) is almost complete. The distribution is rapid, Vd is about 1 L/kg (in patients with heart failure it is below). The protein binding depends on the concentration of the active substance in the plasma and is 60-80%. Spinal Anaesthesia Tray (Lidocaine Hydrochloride) metabolized mainly in the liver with the formation of active metabolites, that may contribute to the manifestation of the therapeutic and toxic effects, especially after the infusion for 24 hours or more.

T_1/2 tends to be two phases with the phase distribution of 9.7 min. In general T_1/2 depends on the dose is 1-2 hours and can grow up to 3 hours or more during prolonged intravenous infusion (over 24 h). Spinal Anaesthesia Tray (Lidocaine Hydrochloride) excreted by the kidneys as metabolites, 10% unchanged.

Why is Spinal Anaesthesia Tray prescribed?

In cardiological practice: treatment and prevention of ventricular arrhythmias (extrasystoles, tachycardia, atrial flutter, atrial fibrillation), including in acute myocardial infarction, implantation of artificial pacemaker in the glycoside intoxication, narcosis.

Anaesthesia: terminal, infiltration, conduction, spinal (epidural) anesthesia in surgery, obstetrics and gynecology, urology, ophthalmology, dentistry, otolaryngology, blockade of peripheral nerves and ganglion.

Dosage and administration

As an anti-arrhythmic medicine for adult with the introduction of a loading dose by IV - 1-2 mg / kg over 3-4 minutes; the average single dose is 80 mg. Then immediately transferred to drip infusion at a rate of 20-55 mg / kg / min. Drip infusion can be carried out within 24-36 hours. If necessary, against the background of drop infusions can repeat IV jet injection of Spinal Anaesthesia Tray 40 mg after 10 minutes after the first loading dose.

IM is introduced to 2-4 mg / kg, if necessary, repeated administration is possible through 60-90 minutes.

For children with IV injection loading dose - 1 mg / kg, if necessary, it may be repeated administration in 5 min.

For continuous intravenous infusion (usually following the introduction of a loading dose) - 20-30 mg / kg / min.

For use in surgical and obstetric practice, dentistry, ENT practice, dosing regimen set individually, depending on the evidence, the clinical situation and used the dosage form.

Maximum dose: for adults for IV injections the loading dose is 100 mg, in a subsequent drop infusion it is 2 mg / min; when IM administration - 300 mg (about 4.5 mg / kg) for 1 h.

For children in case of reintroduction the loading dose every 5 minutes, the total dose is 3 mg / kg; by continuous intravenous infusion (usually following the introduction of a loading dose) - 50 mg / kg / min.

Spinal Anaesthesia Tray (Lidocaine Hydrochloride) side effects, adverse reactions

CNS and peripheral nervous system: dizziness, headache, weakness, motor restlessness, nystagmus, loss of consciousness, drowsiness, visual and auditory disturbances, tremor, trismus, seizures (risk of their development against the backdrop of increasing hypercapnia and acidosis), a syndrome of "cauda equina" (paralysis of the legs, paresthesia), paralysis of respiratory muscles, respiratory arrest, a block of motor and sensitive, respiratory paralysis (usually develops in the subarachnoid anesthesia), numb tongue (when used in dentistry).

Cardiovascular system: increased or decreased blood pressure, tachycardia if used with a vasoconstrictor, peripheral vasodilatation, collapse, chest pain.

Digestive system: nausea, vomiting, involuntary defecation.

Allergic reactions: skin rash, hives (on skin and mucous membranes), itching, angioedema, anaphylactic shock.

Local reactions: during spinal anesthesia - a pain in the back, with an epidural anesthesia - a random hit in the subarachnoid space, when applied topically in urology - urethritis.

Other: incontinent, methemoglobinemia, persistent anesthesia, decreased libido and / or potency, respiratory depression, until the stop, hypothermia; during anesthesia in dentistry: numbness and paresthesia of the lips and tongue, the lengthening of anesthesia.

Spinal Anaesthesia Tray contraindications

Severe bleeding, shock, hypotension, infection of the proposed injection site, marked bradycardia, cardiogenic shock, severe forms of chronic heart failure, SSS in elderly patients, AV-block II and III degree (except in cases when the probe was introduced to stimulate the ventricles), severe liver function abnormalities.

For subarachnoid anesthesia - complete heart block, bleeding, hypotension, shock, infection of the venue lumbar puncture, septicemia.

Increased sensitivity to Spinal Anaesthesia Tray (Lidocaine Hydrochloride) and other amide type local anesthetics.

Using during pregnancy and breastfeeding

During pregnancy and lactation be used only for health reasons. Spinal Anaesthesia Tray is excreted in breast milk.

In obstetric practice used with caution in paracervical for violations of fetal development, placental insufficiency, prematurity, postmaturity, gestosis.

Category effects on the fetus by FDA - B.

Special instructions

Use with caution in liver disease and kidney failure, hypovolemia, severe heart failure, in violation of the contractility of genetic susceptibility to malignant hyperthermia. In children, debilitated patients, elderly patients are required in dosage adjustment in accordance with the age and physical status. When injected into vascularized tissue it is recommended an aspiration test.

Spinal Anaesthesia Tray drug interactions

Beta-blockers increase the risk of bradycardia and hypotension. Norepinephrine and beta-blockers by reducing hepatic blood flow decrease (increased toxicity), isadrine and glucagon - increase the clearance of Spinal Anaesthesia Tray (Lidocaine Hydrochloride). Cimetidine increases the plasma concentration of Spinal Anaesthesia Tray (Lidocaine Hydrochloride) (displaces from its association with proteins and slows inactivation in the liver). Barbiturates causing induction of microsomal enzymes stimulate the degradation of Spinal Anaesthesia Tray (Lidocaine Hydrochloride) and reduce its activity. Anticonvulsants (hydantoin derivatives) accelerate the biotransformation in the liver (decreased concentration in the blood), for IV injections it may increases cardiodepressive action of Spinal Anaesthesia Tray (Lidocaine Hydrochloride). Antiarrhythmics (amiodarone, verapamil, quinidine, aymalin) potentiate cardiac depression. Combination with novocainamide may cause CNS excitement and hallucinations. Spinal Anaesthesia Tray (Lidocaine Hydrochloride) strengthens the inhibitory effect of anesthesia (hexobarbital, thiopental sodium), hypnotics and sedatives on the respiratory center, weakens the cardiac effects of digitoxin, enhances muscle relaxation caused by drugs curare like (possible paralysis of respiratory muscles). MAO inhibitors prolong local anesthesia.

Spinal Anaesthesia Tray in case of emergency / overdose

Symptoms: psychomotor agitation, dizziness, weakness, decreased blood pressure, tremors, tonic-clonic convulsions, coma, collapse, possible AV blockade, CNS depression, respiratory arrest.

Treatment: discontinuation, pulmonary ventilation, oxygen therapy, anticonvulsants, vasoconstrictors (norepinephrine, mezaton), when bradycardia - anticholinergics (atropine). It is possible to carry out intubation, mechanical ventilation, resuscitation. Dialysis is ineffective.

Povidone-Iodine:

• Active ingredient
• Purpose
• Use
• Warnings
• Directions
• Other information
• Inactive ingredients
• Spinal Anaesthesia Tray (Povidone-Iodine) reviews

Active ingredient

Purpose

Antiseptic

Use

Warnings

Do not use

• if allergic to iodine
• in the eyes

Avoid pooling beneath patient

Ask a doctor before use if injuries are

• deep or puncture wounds
• serious burns
  

Stop use and ask a doctor if

• redness, irritation, swelling or pain persists or increases
• infection occurs
  

Keep out of reach of children. In case of accidental ingestion, seek professional assistance or consult a poison control center immediately.

Directions

Other information

• 1 percent titratable iodine
• latex free
• for hospital or professional use only
  

Inactive ingredients

citric acid, disodium phosphate, nonoxynol-9, sodium hydroxide, water

1-800-760-3236 (Mon to Fri 8:30 AM-5:00 PM EST)

THREE Spinal Anaesthesia Tray (Povidone-Iodine) SWABSTICKS

Three 4-inch saturated swabsticks

STERILE unless opened or damaged.

3/4 FLUID OUNCE Spinal Anaesthesia Tray (Povidone-Iodine) SOLUTION

0.75 Fl. oz. (22.5 mL)

STERILE unless opened or damaged.

Three Spinal Anaesthesia Tray (Povidone-Iodine) Swabsticks 3/4 Fluid Ounce Spinal Anaesthesia Tray (Povidone-Iodine) Solution

Total Joint Prep Kit

Total Joint Prep Kit

Tetracaine Hydrochloride:

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Overdosage
• Description
• Clinical pharmacology
• Non-clinical toxicology
• Clinical studies
• How supplied/storage and handling
• Patient counseling information
• Spinal Anaesthesia Tray (Tetracaine Hydrochloride) reviews

1 INDICATIONS AND USAGE

Spinal Anaesthesia Tray (Tetracaine Hydrochloride) ^TM is indicated for regional anesthesia when performing a restorative procedure on Teeth 4-13 and A-J in adults and children who weigh 40 kg or more.

Spinal Anaesthesia Tray (Tetracaine Hydrochloride) contains Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl, an ester local anesthetic, and oxymetazoline HCl, a vasoconstrictor. Spinal Anaesthesia Tray (Tetracaine Hydrochloride) is indicated for regional anesthesia when performing a restorative procedure on Teeth 4-13 and A-J in adults and children who weigh 40 kg or more ( 1).

2 DOSAGE AND ADMINISTRATION

Spinal Anaesthesia Tray is for intranasal use only ( 2). Administer Spinal Anaesthesia Tray (Tetracaine Hydrochloride) ipsilateral (on the same side) to the maxillary tooth on which the dental procedure will be performed.

2.1 Important Dosage and Administration Instructions

• Spinal Anaesthesia Tray (Tetracaine Hydrochloride) is for intranasal use only.
• Administer ipsilateral (same side) to the maxillary tooth on which the dental procedure will be performed.
• Wait 10 minutes after administration of Spinal Anaesthesia Tray (Tetracaine Hydrochloride) to perform a test drill to confirm that the tooth involved is anesthetized. A patient may not experience the same sensations of numbness or tingling of the lips and cheeks associated with injectable dental anesthetics.

2.2 Dosing in Adults

• 2 sprays (0.2 mL each) administered 4 to 5 minutes apart in the nostril ipsilateral to the maxillary tooth on which the dental procedure will be performed. Initiate the dental procedure 10 minutes after the second spray.
• 1 additional spray (0.2 mL) if adequate anesthesia to initiate the dental procedure has not been achieved 10 minutes after the second spray.

2.3 Dosing in Children

• 2 sprays (0.2 mL each) administered 4 to 5 minutes apart in the nostril ipsilateral to the maxillary tooth on which the dental procedure will be performed. Initiate the dental procedure 10 minutes after the second spray.

3 DOSAGE FORMS AND STRENGTHS

Spinal Anaesthesia Tray (Tetracaine Hydrochloride) Nasal Spray is a pre-filled, single-use, intranasal sprayer containing a clear 0.2 mL aqueous solution at pH 6.0 ± 1.0 comprising 30 mg/mL of Spinal Anaesthesia Tray (Tetracaine Hydrochloride) hydrochloride and 0.5 mg/mL of oxymetazoline hydrochloride (equivalent to 26.4 mg/mL Spinal Anaesthesia Tray (Tetracaine Hydrochloride) and 0.44 mg/mL oxymetazoline).

Each nasal spray unit delivers one 0.2 mL spray.

Each 0.2 mL spray contains 6 mg Spinal Anaesthesia Tray (Tetracaine Hydrochloride) hydrochloride (equivalent to 5.27 mg Spinal Anaesthesia Tray (Tetracaine Hydrochloride)) and 0.1 mg oxymetazoline hydrochloride (equivalent to 0.088 mg oxymetazoline).

Nasal spray in pre-filled, single-use sprayer: 6 mg Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl and 0.1 mg oxymetazoline HCl (equivalent to 5.27 mg Spinal Anaesthesia Tray (Tetracaine Hydrochloride) and 0.088 mg oxymetazoline) in each 0.2 mL spray ( 3).

4 CONTRAINDICATIONS

Spinal Anaesthesia Tray (Tetracaine Hydrochloride) is contraindicated in patients with a history of allergy to or intolerance of Spinal Anaesthesia Tray (Tetracaine Hydrochloride), benzyl alcohol, other ester local anesthetics, p-aminobenzoic acid (PABA), oxymetazoline, or any other component of the product .

Known hypersensitivity to Spinal Anaesthesia Tray (Tetracaine Hydrochloride), benzyl alcohol, other ester local anesthetics, p-aminobenzoic acid (PABA), oxymetazoline, or any other component of the product ( 4).

5 WARNINGS AND PRECAUTIONS

Hypertension and Thyroid Disease: Shown to increase blood pressure in some clinical trial patients. Monitor blood pressure. Use in patients with inadequately controlled hypertension or active thyroid disease is not advised.

Epistaxis: Use is not recommended in patients with a history of frequent nose bleeds (≥5 per month). If a decision to use is made, monitor these patients carefully ( 5.2).

Dysphagia: Carefully monitor patients for dysphagia ( 5.3).

Methemoglobinemia: May cause methemoglobinemia, particularly when used with methemoglobin-inducing agents. Use in patients with history of congenital or idiopathic methemoglobinemia not advised. If central cyanosis unresponsive to oxygen therapy occurs, suspect methemoglobinemia, confirm diagnosis with CO-oximetry, and treat with a standard clinical regimen ( 5.4).

Anaphylactic Reactions: Seek emergency help if an anaphylactic reaction occurs ( 5.5).

5.1 Risk of Hypertension

Spinal Anaesthesia Tray (Tetracaine Hydrochloride) has not been studied in Phase 3 trials in adult dental patients with blood pressure greater than 150/100 or in those with inadequately controlled active thyroid disease. Spinal Anaesthesia Tray (Tetracaine Hydrochloride) has been shown to increase blood pressure in some patients in clinical trials. Monitor patients for increased blood pressure. Use in patients with uncontrolled hypertension or inadequately controlled active thyroid disease of any type is not advised .

5.2 Epistaxis

In clinical trials, epistaxis occurred more frequently with Spinal Anaesthesia Tray than placebo. Either do not use Spinal Anaesthesia Tray (Tetracaine Hydrochloride) in patients with a history of frequent nose bleeds (≥ 5 per month) or monitor patients with frequent nose bleeds more carefully if Spinal Anaesthesia Tray (Tetracaine Hydrochloride) is used. [see Adverse Reactions ( 6.1 )].

5.3 Dysphagia

In clinical trials, dysphagia occurred more frequently with Spinal Anaesthesia Tray (Tetracaine Hydrochloride) than placebo. Carefully monitor patients for this adverse reaction.

5.4 Methemoglobinemia

Spinal Anaesthesia Tray may cause methemoglobinemia, particularly in conjunction with methemoglobin-inducing agents. Based on the literature, patients with glucose-6-phosphate dehydrogenase deficiency or congenital or idiopathic methemoglobinemia are more susceptible to drug-induced methemoglobinemia. Use of Spinal Anaesthesia Tray (Tetracaine Hydrochloride) in patients with a history of congenital or idiopathic methemoglobinemia is not advised.

Patients taking concomitant drugs associated with drug-induced methemoglobinemia, such as sulfonamides, acetaminophen, acetanilide, aniline dyes, benzocaine, chloroquine, dapsone, naphthalene, nitrates and nitrites, nitrofurantoin, nitroglycerin, nitroprusside, pamaquine, p-aminosalicylic acid, phenacetin, phenobarbital, phenytoin, primaquine, and quinine, may be at greater risk for developing methemoglobinemia.

Initial signs and symptoms of methemoglobinemia (which may be delayed for up to several hours following exposure) are characterized by a slate grey cyanosis seen in, e.g., buccal mucous membranes, lips and nail beds. In severe cases, symptoms may include central cyanosis, headache, lethargy, dizziness, fatigue, syncope, dyspnea, CNS depression, seizures, dysrythmia and shock. Methemoglobinemia should be considered if central cyanosis unresponsive to oxygen therapy occurs, especially if methemoglobinemia-inducing agents have been used. Calculated oxygen saturation and pulse oximetry are inaccurate in the identification of methemoglobinemia. Confirm diagnosis by measuring methemoglobin level with co-oximetry. Normally, methemoglobinemia levels are <1%, and cyanosis may not be evident until a level of at least 10% is present.

Treat clinically significant symptoms of methemoglobinemia with a standard clinical regimen such as a slow intravenous infusion of methylene blue at a dosage of 1-2 mg/kg given over a 5 minute period.

5.5 Anaphylactic Reactions

Allergic or anaphylactic reactions have been associated with Spinal Anaesthesia Tray (Tetracaine Hydrochloride), and may occur with other components of Spinal Anaesthesia Tray (Tetracaine Hydrochloride). They are characterized by urticaria, angioedema, bronchospasm, and shock. If an allergic reaction occurs, seek emergency help immediately.

6 ADVERSE REACTIONS

The following adverse reactions are described elsewhere in the labeling:

• Hypertension
• Epistaxis
• Dysphagia
• Methemoglobinemia
• Anaphylatic Reactions

The most common adverse reactions occurring in >10% of patients include rhinorrhea, nasal congestion, nasal discomfort, oropharyngeal pain, and lacrimation increased ( 6).

Transient, asymptomatic elevations in systolic blood pressure (≥ 25 mm Hg from baseline) and diastolic blood pressures (≥ 15 mm Hg from baseline) have been reported ( 6).

To report SUSPECTED ADVERSE REACTIONS, contact St. Renatus, LLC at 800-865-4925 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The adverse reactions information described below is from Phase 3 randomized, controlled clinical trials [see Clinical Studies ( 14)] . These data reflect exposure to Spinal Anaesthesia Tray (Tetracaine Hydrochloride) in 154 adult dental patients and 20 pediatric dental patients (aged 7 to 17 years) with a need for an operative restorative dental procedure requiring local anesthesia for a single vital maxillary tooth (other than a maxillary first, second, or third molar) with no evidence of pulpal pathology. .

Common Adverse Reactions in Adult Dental Patients and Pediatric Patients Weighing 40 kg or More

The most common adverse reactions to occur in Phase 3 trials with Spinal Anaesthesia Tray (Tetracaine Hydrochloride) in adult dental patients and pediatric dental patients weighing 40 kg or more were rhinorrhea, nasal congestion, nasal discomfort, oropharyngeal pain, and lacrimation increased [ Table 1] .

No serious adverse events with Spinal Anaesthesia Tray (Tetracaine Hydrochloride) have occurred .

Intranasal ulcerations, some of which were transient, were noted to have occurred following treatment with Spinal Anaesthesia Tray (Tetracaine Hydrochloride). In Phase 3 trials, 6 (3%) patients who received Spinal Anaesthesia Tray (Tetracaine Hydrochloride), but no patients who received placebo, developed nasal ulcers that were present on exam the same day as Spinal Anaesthesia Tray (Tetracaine Hydrochloride) dosing. Three (2%) Spinal Anaesthesia Tray (Tetracaine Hydrochloride) and 2 (2%) placebo-treated patients without nasal ulcerations on the day of Spinal Anaesthesia Tray (Tetracaine Hydrochloride) or placebo dosing were observed to have nasal ulcerations at the next day follow-up visit.

Less Common Adverse Reactions in Phase 3 Clinical Trials Adult Dental Patients and Pediatric Dental Patients Weighing 40 kg or More

Dysphagia (i.e., the sensation of difficult swallowing) is a notable adverse reaction reported in Phase 3 trials, occurring in 1.15% of patients.

For medical advice about adverse reactions, contact your medical professional. To report SUSPECTED ADVERSE REACTIONS, contact St. Renatus, LLC at 800-865-4925 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch/.

7 DRUG INTERACTIONS

Monoamine oxidase inhibitors : Concomitant use of MAOIs, nonselective beta adrenergic antagonists, or tricyclic antidepressants may cause hypertension and is not recommended ( 7.1).

Oxymetazoline-containing products: Discontinue use 24 hours prior to Spinal Anaesthesia Tray (Tetracaine Hydrochloride) administration ( 7.2).

Intranasal products: Avoid concomitant use ( 7.3).

7.1 Monoamine Oxidase Inhibitors

Use of Spinal Anaesthesia Tray (Tetracaine Hydrochloride) in combination with monoamine oxidase inhibitors (MAOIs), nonselective beta adrenergic antagonists, or tricyclic antidepressants may cause hypertension and is not recommended. Alternative anesthetic agents should be chosen for patients who cannot discontinue use of MAOIs, nonselective beta adrenergic antagonists, or tricyclic antidepressants.

7.2 Oxymetazoline-containing Products

Concomitant use with other oxymetazoline-containing products has not been adequately studied. Use of Spinal Anaesthesia Tray (Tetracaine Hydrochloride) with other products containing oxymetazoline may increase risk of hypertension, bradycardia, and other adverse events associated with oxymetazoline. Discontinue use 24 hours prior to administration of Spinal Anaesthesia Tray (Tetracaine Hydrochloride).

7.3 Intranasal Products

Oxymetazoline has been known to slow the rate, but not affect the extent of absorption of concomitantly administered intranasal products. Do not administer other intranasal products with Spinal Anaesthesia Tray (Tetracaine Hydrochloride).

7.4 Drugs That May Cause Methemoglobinemia When Used with Spinal Anaesthesia Tray

Spinal Anaesthesia Tray (Tetracaine Hydrochloride) may cause methemoglobinemia, particularly in conjunction with methemoglobin-inducing agents such as sulfonamides, acetaminophen, acetanilide, aniline dyes, benzocaine, chloroquine, dapsone, naphthalene, nitrates and nitrites, nitrofurantoin, nitroglycerin, nitroprusside, pamaquine, p- aminosalicylic acid, phenacetin, phenobarbital, phenytoin, primaquine, and quinine. Monitor patients carefully for signs of methemoglobinemia if Spinal Anaesthesia Tray (Tetracaine Hydrochloride) is used in the setting of these drugs.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

Limited published data on Spinal Anaesthesia Tray use in pregnant women are not sufficient to inform any risks. Published epidemiologic studies of nasal oxymetazoline used as a decongestant during pregnancy do not identify a consistent association with any specific malformation or pattern of malformations . In animal reproduction and development studies, oxymetazoline given subcutaneously to rats during the period of organogenesis caused structural abnormalities at a dose approximately 7.6 times the exposure of oxymetazoline HCl at the 0.3 mg maximum recommended human dose (MRHD) of Spinal Anaesthesia Tray (Tetracaine Hydrochloride). In a pre- and post-natal development study, oxymetazoline given subcutaneously to rats caused embryo-fetal toxicity manifested by reduced implantation sites and live litter sizes at approximately 1.5 times the MRHD and increased pup mortality at 6 times the MRHD. No adverse developmental effects were observed following subcutaneous administration of Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl only to rats and rabbits during organogenesis at 32 and 6 times, respectively, the estimated exposure of Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl at the 18 mg MRHD of Spinal Anaesthesia Tray (Tetracaine Hydrochloride) .

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 and to 20%, respectively.

Data

Human Data

Published epidemiologic studies of nasal oxymetazoline used as a decongestant during pregnancy do not identify a consistent association with any specific malformation or pattern of malformations. These data are limited by the small number of cases exposed, multiple comparisons which may have resulted in chance findings, and analyses based on decongestants as a group.

Animal Data

In an embryo-fetal development study, pregnant rats were administered subcutaneous doses of oxymetazoline HCl only at 0.1 mg/kg, Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl only at 7.5 mg/kg, or oxymetazoline HCl at 0.01, 0.03, and 0.1 mg/kg/day in combination with 7.5 mg/kg Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl during the period of organogenesis (Gestational Days [GD] 7-17). Oxymetazoline HCl treatment at 0.1 mg/kg/day (7.6 times the oxymetazoline AUC exposure at the maximum recommended human dose [MRHD] of Spinal Anaesthesia Tray (Tetracaine Hydrochloride) [3 mg oxymetazoline HCl and 18 mg Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl]) caused reduced fetal weight and structural abnormalities including external and skeletal malformations (e.g., short forelimb digits, fused arches in thoracic vertebrae, fused ribs, and irregular number of ribs), and variations (e.g., irregularly shaped arches and increased bifid centra in thoracic vertebrae, and un-ossified forelimb phalanx) in the presence of maternal toxicity (reduced food consumption, body weight gain, and absolute body weight); however, the structural abnormality findings cannot be clearly attributed to the maternal toxicity. Adverse developmental effects were not observed when pregnant rats were co-administered the same dose of oxymetazoline HCl in combination with 7.5 mg/kg/day Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl, or with 7.5 mg/kg/day Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl alone. The no-observed-adverse-effect-level (NOAEL) for fetal effects was 0.03 mg/kg/day oxymetazoline HCl (1.5 times the oxymetazoline AUC exposure at the MRHD) and 7.5 mg/kg/day Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl (30 times the AUC exposure as measured by PBBA [major Spinal Anaesthesia Tray (Tetracaine Hydrochloride) metabolite] at the MRHD).

In other embryo-fetal development studies, Spinal Anaesthesia Tray (Tetracaine Hydrochloride) base alone administered subcutaneously did not cause structural abnormalities in rats at doses up to 10 mg/kg/day (approximately 6.1 times the MRHD level of 18 mg Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl by body surface area (BSA) comparison) or in rabbits at subcutaneous doses up to 5 mg/kg/day (approximately 6.1 times the MRHD level by BSA comparison).

In a prenatal and postnatal development study, pregnant rats were given subcutaneous doses of oxymetazoline HCl only at 0.1 mg/kg/day, Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl only at 7.5 mg/kg/day, and oxymetazoline HCl at 0.01, 0.03, and 0.1 mg/kg/day in combination with 7.5 mg/kg/day Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl from GD 7 to Lactation Day [LD] 20 (corresponding to the beginning of organogenesis through parturition and subsequent pup weaning). Oxymetazoline HCl treatment decreased the mean number of implant sites/litter at ≥ 0.03 mg/kg (≥ 1.5 times the oxymetazoline AUC exposure at the MRHD) when administered with 7.5 mg/kg Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl (approximately 9%) and without Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl (5.5%), which resulted in a reduction in live litter sizes in these groups. At the end of the lactation period, fetal body weights were significantly decreased at 0.1 mg/kg oxymetazoline HCl (6 times the oxymetazoline AUC exposure at the MRHD) when administered alone (19%) and co-administered with 7.5 mg/kg/day Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl (11%). In addition, a decrease in pup survival was observed at the 0.1/7.5 mg/kg oxymetazoline HCl/tetracaine HCl dose (91.9%) compared to the control (99.6%), but no effects in any other groups. Maternal toxicity (e.g., mortality and reduced body weight gain, absolute body weight and food consumption) occurred in groups administered 0.1 mg/kg/day oxymetazoline HCl; however, the adverse developmental findings observed at this dose cannot clearly be attributed to the maternal toxicity. There were no adverse effects on sexual maturation, neurobehavioral, or reproductive function in the offspring at any maternal dose. The no-effect level for oxymetazoline HCl for maternal reproduction was 0.01 mg/kg/day (0.5 times oxymetazoline AUC exposure at the MRHD) and for pup growth and development was 0.03 mg/kg/day (1.5 times oxymetazoline AUC exposure at the MRHD). The no-effect level for Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl for maternal reproduction and pup growth and development was 7.5 mg/kg/day (12 times the AUC exposure as measured by PBBA at the MRHD).

8.2 Lactation

Risk Summary

There are no data on the presence of Spinal Anaesthesia Tray (Tetracaine Hydrochloride), oxymetazoline, or their metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. Detectable levels of oxymetazoline, Spinal Anaesthesia Tray (Tetracaine Hydrochloride) and the major metabolite of Spinal Anaesthesia Tray (Tetracaine Hydrochloride), p-butylaminobenzoic acid (PBBA), were found in the milk of lactating rats following subcutaneous administration of oxymetazoline HCl in combination with Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl during the period of organogenesis through parturition and subsequent pup weaning . Due to species-specific differences in lactation physiology, animal data may not reliably predict drug levels in human milk.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Spinal Anaesthesia Tray (Tetracaine Hydrochloride) and any potential adverse effects on the breastfed infant from Spinal Anaesthesia Tray (Tetracaine Hydrochloride) or from the underlying maternal condition.

Data

In a pre- and post-natal development study, rats were given oxymetazoline HCl subcutaneously at doses of 0.01, 0.03, and 0.1 mg/kg/day (0.6, 1.5, and 7.6 times, respectively, the oxymetazoline AUC exposure at the MRHD) in combination with 7.5 mg/kg Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl (12 times the AUC exposure as measured by PBBA at the MRHD) from Gestational Day [GD] 7 to Lactation Day [LD] 20. Concentrations of oxymetazoline, Spinal Anaesthesia Tray (Tetracaine Hydrochloride), and PBBA were measured in the milk of lactating rats at approximately 2 hours postdose on LD 15. The concentrations of oxymetazoline were generally dose dependent (2.5, 7.0, and 33.8 ng/mL at 0.01, 0.03, and 0.1 mg/kg/day, respectively). The concentrations of Spinal Anaesthesia Tray (Tetracaine Hydrochloride) and PBBA were generally similar across all 7.5 mg/kg/day Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl dosing groups regardless of the presence of oxymetazoline (54.2 – 72.9 ng/mL for Spinal Anaesthesia Tray (Tetracaine Hydrochloride), and 100.5 – 131.2 ng/mL for PBBA).

8.3 Females and Males of Reproductive Potential

Infertility

No information is available on fertility effects in humans.

Females

Based on animal data, Spinal Anaesthesia Tray may reduce fertility in females of reproductive potential. In female rats, decreased fertility noted as a decrease in litter size occurred at 0.7 times the oxymetazoline AUC exposure at the MRHD of Spinal Anaesthesia Tray (Tetracaine Hydrochloride). It is not known if the effects on fertility are reversible [ see Nonclinical Toxicology ( 13.1)] .

Males

Based on animal data, Spinal Anaesthesia Tray (Tetracaine Hydrochloride) may reduce male fertility. In male rats, decreased sperm motility and sperm concentration occurred at approximately 2 times the oxymetazoline AUC exposure at the MRHD of Spinal Anaesthesia Tray (Tetracaine Hydrochloride) .

8.4 Pediatric Use

Spinal Anaesthesia Tray (Tetracaine Hydrochloride) has not been studied in pediatric patients under 3 years of age and is not advised for use in pediatric patients weighing less than 40 kg because efficacy has not been demonstrated in these patients .

8.5 Geriatric Use

Clinical studies of Spinal Anaesthesia Tray did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Monitor geriatric patients for signs of local anesthetic toxicity, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Of note, comparisons of Spinal Anaesthesia Tray (Tetracaine Hydrochloride) safety and efficacy results were generally similar among dental patients who were > 50 years old (n=66) and ≤ 50 years old (n=148). However, a trend toward a higher incidence of notable increases in systolic blood pressure was observed in dental patients > 50 years of age compared with patients ≤ 50 years of age (16.6% vs 1.4, respectively) [see Adverse Reactions ( 6.1 )]. These increases in blood pressure measurements were generally asymptomatic and transient in nature, and all spontaneously resolved without the need for medical intervention [see Clinical Studies ( 14.1 )] .

8.6 Hepatic Disease

Because of an inability to metabolize local anesthetics, those patients with severe hepatic disease may be at a greater risk of developing toxic plasma concentrations of Spinal Anaesthesia Tray (Tetracaine Hydrochloride). Monitor patients with hepatic disease for signs of local anesthetic toxicity.

8.7 Pseudocholinesterase Deficiency

Because of an inability to metabolize local anesthetics, those patients with pseudocholinesterase deficiency may be at a greater risk of developing toxic plasma concentrations of Spinal Anaesthesia Tray (Tetracaine Hydrochloride). Monitor patients with pseudocholinesterase deficiency for signs of local anesthetic toxicity.

10 OVERDOSAGE

No addictive properties have been reported in the literature for either Spinal Anaesthesia Tray (Tetracaine Hydrochloride) or oxymetazoline, but there have been numerous case reports of unintended overdose for both compounds. Side effects in adults and children associated with oxymetazoline overdose include dizziness, chest pain, headaches, myocardial infarction, stroke, visual disturbances, arrhythmia, hypertension, or hypotension. Side effects of Spinal Anaesthesia Tray (Tetracaine Hydrochloride) overdose include rapid circulatory collapse, cardiac arrest, and cerebral events.

Possible rebound nasal congestion, irritation of nasal mucosa, and adverse systemic effects (particularly in children), including serious cardiac events, have been associated with overdosage and/or prolonged or too frequent intranasal use of oxymetazoline containing agents.

Accidental ingestion of imidazoline derivatives (i.e., oxymetazoline, naphazoline, tetrahydrozoline) in children has resulted in serious adverse events requiring hospitalization (e.g., coma, bradycardia, decreased respiration, sedation, and somnolence).

Patients should be instructed to avoid using oxymetazoline-containing products (such as Afrin ^®) and other α-adrenergic agonists within 24 hours prior to their scheduled dental procedure .

Management of an overdose includes close monitoring, supportive care, and symptomatic treatment.

11 DESCRIPTION

Spinal Anaesthesia Tray (Tetracaine Hydrochloride) (tetracaine HCl and oxymetazoline HCl) Nasal Spray is a clear aqueous solution in a pre-filled, single-use intranasal sprayer. The solution pH is 6.0 ± 1.0. The product contains two active ingredients: 30 mg/mL Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl (equivalent to 26.4 mg/mL Spinal Anaesthesia Tray (Tetracaine Hydrochloride)) and 0.5 mg/mL oxymetazoline hydrochloride (equivalent to 0.44 mg/mL oxymetazoline). Each spray delivers 0.2 mL of solution containing 6 mg Spinal Anaesthesia Tray (Tetracaine Hydrochloride) hydrochloride (equivalent to 5.27 mg Spinal Anaesthesia Tray (Tetracaine Hydrochloride)) and 0.1 mg of oxymetazoline hydrochloride (equivalent to 0.088 mg oxymetazoline). The product also contains citric acid, sodium citrate, hydroxyethylcellulose, benzyl alcohol, and water. Sodium hydroxide and/or hydrochloric acid are added for pH adjustment as needed.

Spinal Anaesthesia Tray (Tetracaine Hydrochloride) hydrochloride is an ester local anesthetic. Chemically it is 2-(dimethylamino)ethyl 4-(butylamino)benzoate hydrochloride. Its molecular weight is 300.8 for the hydrochloride salt and 264.4 for the free base. It is freely soluble in water and soluble in ethanol. Its structural formula is:

Oxymetazoline hydrochloride is a vasoconstrictor. Chemically it is 3-[(4,5-dihydro-1 H-imidazol-2-yl)methyl]-6-(1,1,-dimethylethyl)-2,4-dimethylphenol mono-hydrochloride. Its molecular weight is 296.8 for the hydrochloride salt and 260.4 for the free base. It is freely soluble in water and ethanol and has a partition coefficient of 0.1 in octanol/water. Its structural formula is:

Spinal Anaesthesia Tray (Tetracaine Hydrochloride) Hydrochloride Structural Formula Oxymetazoline Hydrochloride Structural Formula

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Spinal Anaesthesia Tray is a local anesthetic of the ester type and exerts its activity by blocking sodium ion channels required for the initiation and conduction of neuronal impulses. Oxymetazoline is an imidazoline derivative with sympathomimetic activity. It is believed to be a mixed α ₁/α ₂-adrenoceptor agonist and, by stimulating adrenergic receptors, it elicits vasoconstriction of dilated arterioles and reduces nasal blood flow.

12.3 Pharmacokinetics

Absorption

Following nasal administration of 0.6 mL Spinal Anaesthesia Tray (Tetracaine Hydrochloride) in adult subjects (n=24), oxymetazoline attained maximum concentrations within approximately 10 minutes following the end of dosing. The observed mean oxymetazoline C _max and AUC _0-inf value were 1.78 ng/mL and 4.24 ng.h/mL, respectively. The observed median T _max was 5 minutes.

Plasma concentrations of Spinal Anaesthesia Tray (Tetracaine Hydrochloride) in all subjects were at or below the limit of assay quantification (0.05 ng/mL). Of all plasma samples analyzed, only one quantifiable Spinal Anaesthesia Tray (Tetracaine Hydrochloride) concentration was observed in a single sample from one subject, which was at the limit of assay quantification. The primary metabolite of Spinal Anaesthesia Tray (Tetracaine Hydrochloride), p-butylaminobenzoic acid (PBBA) achieved peak concentrations within approximately 25 minutes following the end of Spinal Anaesthesia Tray (Tetracaine Hydrochloride) dosing. The observed mean PBBA C _max and AUC _0-inf value were 465 ng/mL and 973 ng.h/mL, respectively. The observed median T _max was 20 minutes.

Distribution

Protein binding and distribution of oxymetazoline and PBBA have not been determined. Plasma protein binding of Spinal Anaesthesia Tray (Tetracaine Hydrochloride) has been reported to be 75% to 85%.

Elimination

The terminal half-life of oxymetazoline in plasma following nasal administration of Spinal Anaesthesia Tray (Tetracaine Hydrochloride) to adult subjects is approximately 5.2 hours.

The elimination half-life and apparent clearance of Spinal Anaesthesia Tray (Tetracaine Hydrochloride) could not be determined after Spinal Anaesthesia Tray (Tetracaine Hydrochloride) administration because it is rapidly and thoroughly hydrolyzed in plasma. The plasma half-life of PBBA is approximately 2.6 hours in adult subjects.

Metabolism

Oxymetazoline is converted to a glucuronide conjugate in vitro by UGT1A9.

Spinal Anaesthesia Tray (Tetracaine Hydrochloride) is rapidly and thoroughly cleaved by esterases in plasma and other tissues to PBBA and dimethylaminoethanol. These metabolites have an unspecified activity.

Excretion

The apparent clearance of oxymetazoline after nasal administration of Spinal Anaesthesia Tray (Tetracaine Hydrochloride) has not been determined. It is thought that the primary route of oxymetazoline elimination at clinically relevant concentrations is by renal excretion.

PBBA clearance cannot be determined after administration of Spinal Anaesthesia Tray (Tetracaine Hydrochloride).

Special Populations

Pediatrics:

In subjects 4-15 years of age (n=18) that received Spinal Anaesthesia Tray (Tetracaine Hydrochloride) doses of 0.1 mL (10 to < 20 kg body weight), 0.2 mL (20 to < 40 kg), or 0.4 mL (≥ 40 kg), oxymetazoline attained maximum concentrations within approximately 10 minutes to 30 minutes (median time) following the end of dosing. The observed oxymetazoline mean C _max values were 0.37 ± 0.43, 0.85 ± 0.45, and 1.2 ± 0.39 ng/mL in the 0.1 mL, 0.2 mL, and 0.4 mL dose groups, respectively. The observed oxymetazoline mean AUC _0-inf values were 0.99 (AUC can be calculated only in one subject), 2.53 ± 1.08, and 2.64 ± 0.41 ng.h/mL in the 0.1 mL, 0.2 mL, and 0.4 mL dose groups, respectively. Mean elimination half-life values for oxymetazoline were approximately 1.6 to 4.3 hours across pediatric dose groups.

Plasma concentrations of Spinal Anaesthesia Tray (Tetracaine Hydrochloride) were below the limit of assay quantification (0.05 ng/mL) in all subjects.

PBBA attained maximum concentrations within approximately 20 minutes to 30 minutes (median time) following the end of dosing. The observed PBBA mean C _max values were 166 ± 71, 345 ± 172, and 365 ± 30 ng/mL in the 0.1 mL, 0.2 mL, and 0.4 mL dose groups, respectively. The observed PBBA mean AUC _0-inf values were 529 ± 222, 826 ± 606, and 665 ± 86 ng.h/mL in the 0.1 mL, 0.2 mL, and 0.4 mL dose groups, respectively. Mean elimination half-life values for PBBA were approximately 1.6 to 2.8 hours across pediatric dose groups.

Elderly: The pharmacokinetics of Spinal Anaesthesia Tray (Tetracaine Hydrochloride) were not evaluated in subjects greater than 50 years of age.

Renal or Hepatic Impairment: The pharmacokinetics of oxymetazoline, Spinal Anaesthesia Tray (Tetracaine Hydrochloride), and PBBA were not evaluated after nasal administration of Spinal Anaesthesia Tray (Tetracaine Hydrochloride) in subjects with renal or hepatic impairment.

Race: There were insufficient data to evaluate the effect of race on oxymetazoline, Spinal Anaesthesia Tray (Tetracaine Hydrochloride), and PBBA pharmacokinetics after nasal administration of Spinal Anaesthesia Tray (Tetracaine Hydrochloride).

13 NON-CLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Long-term studies in animals have not been performed to evaluate the carcinogenic potential of Spinal Anaesthesia Tray (Tetracaine Hydrochloride) or oxymetazoline.

Mutagenesis

Spinal Anaesthesia Tray (Tetracaine Hydrochloride) base was negative in the in vitro Ames bacterial reverse mutation assay and the in vivo mouse micronucleus assay. In the in vitro chromosome aberration assay using Chinese hamster ovary cells, Spinal Anaesthesia Tray (Tetracaine Hydrochloride) base was negative in the absence of metabolic activation, and equivocal in the presence of metabolic activation. No studies have been conducted to evaluate the mutagenic potential of oxymetazoline.

Impairment of Fertility

Male and female rats were given subcutaneous doses of oxymetazoline HCl alone at 0.1 mg/kg/day, Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl alone at 7.5 mg/kg/day, or the combination of oxymetazoline HCl at 0.01, 0.03, or 0.1 mg/kg/day oxymetazoline with 7.5 mg/kg/day Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl prior to and during mating. Oxymetazoline HCl at ≥ 0.03 mg/kg/day reduced the percentage of motile sperm and sperm counts at 2 times the oxymetazoline AUC exposure at the MRHD of Spinal Anaesthesia Tray (Tetracaine Hydrochloride). There were no effects on male mating behavior at any dose tested. The no-effect level for sperm effects was 0.01 mg/kg/day (0.7 times the oxymetazoline AUC exposure at the MRHD of Spinal Anaesthesia Tray (Tetracaine Hydrochloride)).

In female rats, a reduction in the number of viable embryos was observed at oxymetazoline AUC exposures equivalent to 0.7 times the MRHD and higher, given alone or in combination with Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl. Reduced numbers of corpora lutea and implantation sites were observed at 7.5 times the oxymetazoline AUC exposure at the MRHD in animals given oxymetazoline HCl alone or in combination with Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl. These effects were attributed to oxymetazoline HCl because similar effects were not observed in rats given Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl alone. A no-effect level for fertility in female rats was not established in this study.

No effects on male or female fertility were attributed to Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl at 7.5 mg/kg/day (28 and 33 times the AUC exposure for males and females, respectively, as measured by PBBA [major Spinal Anaesthesia Tray (Tetracaine Hydrochloride) metabolite] at the MRHD of Spinal Anaesthesia Tray (Tetracaine Hydrochloride)).

14 CLINICAL STUDIES

The efficacy of Spinal Anaesthesia Tray Nasal Spray for regional anesthesia when performing a restorative procedure on Teeth 4-13 and A-J has been evaluated in three adult dental patient studies, as well as one pediatric dental patient study. The primary endpoint for all four studies was the successful completion of a restorative operative dental procedure without the need for a rescue injection. One adult dental study was terminated early for reasons related to the administration of Spinal Anaesthesia Tray (Tetracaine Hydrochloride). Unlike the other studies conducted, in this study all three sprays were delivered horizontally.

14.1 Studies in Adults

Study 1

Study 1 was a Phase 3, multicenter, randomized, double-blind, placebo and active-controlled, parallel-groups study designed to compare the efficacy and safety of intranasally administered Spinal Anaesthesia Tray (Tetracaine Hydrochloride) to both Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl alone and placebo, for providing dental anesthesia sufficient to allow completion of the standard dental procedure on a single maxillary tooth (#4-13) in adults.

A total of 110 patients were enrolled in two clinical centers and randomized to receive three 0.2 mL intranasal sprays of either Spinal Anaesthesia Tray (Tetracaine Hydrochloride) (n=44), Spinal Anaesthesia Tray (Tetracaine Hydrochloride) alone (n=44), or placebo (n=22). All randomized patients completed the study dental procedure.

Fifty-three percent (53%) of randomized patients were female and 76% were White, with a mean age of 35 years (range 18 to 73 years).

Eighty-four percent (95% CI: 70%, 93%) of Spinal Anaesthesia Tray (Tetracaine Hydrochloride) patients were able to complete the dental procedure without the need for rescue medication compared to 27% (95% CI: 15%, 43%) who received Spinal Anaesthesia Tray (Tetracaine Hydrochloride) alone and 27% (95% CI: 11%, 50%) who received placebo.

Spinal Anaesthesia Tray (Tetracaine Hydrochloride) had a lower success rate for dental procedures on the 2 ^nd pre-molar (teeth #4 and #13) compared with more anterior teeth (#5 through #12): 63% for the 2 ^nd pre-molars vs 96% for more anterior teeth.

In this trial, the median duration of a dental procedure successfully completed with Spinal Anaesthesia Tray (Tetracaine Hydrochloride) was 11 minutes, although one successfully completed dental procedure was as long as 43 minutes. Of the people that needed rescue medication in the Spinal Anaesthesia Tray (Tetracaine Hydrochloride) arm, they required it within the first 6 minutes following the start of the dental procedure.

Study 2

Study 2 was a Phase 3, multicenter, randomized, double-blind, parallel-groups study designed to compare the efficacy and safety of intranasally administered Spinal Anaesthesia Tray (Tetracaine Hydrochloride) to placebo, for providing dental anesthesia sufficient to allow completion of the standard dental procedure on a single maxillary tooth (#4-13) in adults.

A total of 150 adult patients were enrolled at three study centers and received either Spinal Anaesthesia Tray (Tetracaine Hydrochloride) (n=100) or placebo (n=50) as a dose of two or three 0.2 mL intranasal sprays. All except two randomized patients (one each in the Spinal Anaesthesia Tray (Tetracaine Hydrochloride) and placebo groups) completed the study dental procedure.

Fifty-five percent (55%) of randomized patients were female and 63% were White, with a mean age of 41 years (range 18 to 78 years).

Eighty-eight percent (95% CI: 80%, 94%) of Spinal Anaesthesia Tray (Tetracaine Hydrochloride) patients were able to complete the dental procedure without the need for rescue medication compared to 28% (95% CI: 16%, 43%) of patients who received placebo.

Spinal Anaesthesia Tray (Tetracaine Hydrochloride) had a lower success rate for dental procedures on the 2 ^nd pre-molar (teeth #4 and #13) compared with more anterior teeth (#5 through #12): 64% for the 2 ^nd pre-molars vs 96% for more anterior teeth.

14.2 Study in Children

Study 3

Study 3 was a Phase 3, multicenter, randomized, double-blind, parallel-groups study designed to compare the efficacy and safety of intranasally administered Spinal Anaesthesia Tray (Tetracaine Hydrochloride) to placebo for providing dental anesthesia sufficient to allow completion of the standard dental procedure on a single maxillary tooth (permanent teeth 4-13 or primary teeth A-J) for pediatric patients aged 3 through 17.

A total of 90 patients, 3 through 17 years of age inclusive, were enrolled at two study centers. Patients received one or two intranasal sprays of either Spinal Anaesthesia Tray (Tetracaine Hydrochloride) (n=60) or placebo (n=30) based on body weight: one 0.1 mL spray for patients weighing 10 kg to less than 20 kg; two 0.1 mL sprays for 20 kg to less than 40 kg; or two 0.2 mL sprays for patients weighing 40 kg or more. All except one randomized patient in the Spinal Anaesthesia Tray (Tetracaine Hydrochloride) group completed the study dental procedure.

Fifty-one percent (51%) of randomized patients were male and 89% were White, with a mean age of 8 years (range 3 to 17 years).

Even though a greater percentage of patients were able to complete the dental procedure without the need for rescue anesthesia for Spinal Anaesthesia Tray (Tetracaine Hydrochloride): 77% for Spinal Anaesthesia Tray (Tetracaine Hydrochloride) (95% CI: 64%, 87%) compared to 53% for placebo (95% CI: 34%, 72%) an analysis by weight indicated that efficacy was only established for patients weighing 40 kg or more .

16 HOW SUPPLIED/STORAGE AND HANDLING

Spinal Anaesthesia Tray (Tetracaine Hydrochloride) Nasal Spray is supplied as pre-filled, single-use sprayers containing a clear aqueous solution of 30 mg/mL of Spinal Anaesthesia Tray (Tetracaine Hydrochloride) hydrochloride (equivalent to 26.4 mg/mL Spinal Anaesthesia Tray (Tetracaine Hydrochloride)) and 0.5 mg/mL of oxymetazoline hydrochloride (equivalent to 0.44 mg/mL oxymetazoline). Each sprayer delivers 0.2 mL.

The product is available as:

• NDC 69803-100-10: Box of 30 sprayers

Store between 2° and 8°C (36° and 46°F); excursions permitted between 0° and 15°C (32° and 59°F).

Discard any unused solution. DO NOT use if drug is left out at room temperature for more than 5 days.

17 PATIENT COUNSELING INFORMATION

• Inform patients of the likelihood of expected side effects (including runny nose, nasal congestion, mild nose bleeds, dizziness, and/or a sensation of difficulty in swallowing) that should resolve within the same day. Instruct patients to contact their dentist or health care professional if these symptoms persist .
• Advise patients to inform the dental practitioner if they are taking monoamine oxidase inhibitors (MAOIs), nonselective beta adrenergic antagonists, or tricyclic antidepressants .
• Instruct patients to avoid using oxymetazoline-containing products (such as Afrin ^® and other α-adrenergic agonists) within 24 hours prior to their scheduled dental procedure. .
• Advise patients of the signs and symptoms of hypersensitivity reactions and to seek immediate medical attention should they occur .

St. Renatus, LLC

Manufactured for:

St. Renatus, LLC

Fort Collins, CO 80526

Spinal Anaesthesia Tray (Tetracaine Hydrochloride) is a trademark of St. Renatus, LLC.

Principal Display Panel - Box Label

NDC 69803-100-10

Spinal Anaesthesia Tray (Tetracaine Hydrochloride)

(tetracaine HCl and oxymetazoline HCl)

NASAL SPRAY

0.2 mL per sprayer

Containing 6 mg Spinal Anaesthesia Tray (Tetracaine Hydrochloride) HCl and 0.1 mg oxymetazoline HCl

(equivalent to 5.27 mg Spinal Anaesthesia Tray (Tetracaine Hydrochloride) and 0.088 mg oxymetazoline)

Contents: 30 sprayers

Rx only

NOT FOR INJECTION

Store refrigerated at 2 to 8°C (36 to 46°F)

Manufactured for

St. Renatus, LLC

Fort Collins, CO 80526