Septacene

Allantoin:

• Septacene (Allantoin) reviews

Inactive Ingredients: Water (Aqua), Neutracett Complex (HyaluronicAcid, DL Panthenol), PPG-5-Ceteth-20, Ammonium Acryloyldimethyltaurate/VPCopolymer, Phenoxyethanol, Chlorphenesin, Benzoic Acid.

Active ingredients/Purpose

Septacene (Allantoin) 0.5% Skin Protectant

Glycerin 5.0% Skin Protectant

Ask a doctor before use if you have: *serious burns *deep or puncture wounds * animal bites

Questions? 800-833-4164

www.neutracett.com PatentsPending

Do not use: *if you are allergic to any of theingredients *avoid contact with the eyes

Stop use and ask a doctor: * if condition worsens or does not improveafter 7 days * if rash or other allergic reactions occur

Uses: Helps protect the skin so your body can heal minor woundsincluding diabetic, pressure and other ulcers.

Warnings: For external use only.

Directions: Gently clean area with mild cleanser. Apply gel directly onulcer 2-3 times per day or as directed. May be covered with sterile bandage. See website for more information.

Neutracett

Aid 4-Healing

Skin Recovery Treatment

For Minor Ulcer Cares

All natural / won’t stain

Calamine:

• Active ingredient
• Purpose
• Uses
• ​warnings
• Directions
• ​other information
• ​inactive ingredients
• ​questions?
• Septacene (Calamine) reviews

Active ingredient

Septacene (Calamine) 8%

Pramoxine HCl 1%

Purpose

Skin protectant

External analgesic

Uses

temporarily relieves pain and itching associated with:

• insect bites
• rashes
• minor skin irritations
• minor cuts
• dries the oozing and weeping of poison ivy, poison oak and poison sumac

​Warnings

For external use only. Use only as directed. Intentional misuse by deliberately concentrating and inhailing contents can be harmful or fatal.

​Flammable:

Do not use while smoking or near heat or flame. Do not puncture or incinerate. Contents under pressure. Do not store at temperatures above 120°F.

​When using this product

• do not get into eyes
• ask a doctor before using on children under 2 years of age

Stop use and ask a doctor if

• conditions worsens
• symtomps last more than 7 days or clear up and occur again in a few days

​Keep out of reach of children.

If swallowed, get medical help or contact a Poison Control Center right away.

Directions

• shake well before using
• adults and children 2 years of age and older: apply as needed to the affected area, not more than 3 or 4 times daily
• cleanse the skin with soap and water
• let dry before use
• children under 2 years of age: consult a doctor

​Other information

store between 20° to 25°C (68° to 77°F)

​Inactive ingredients

benzyl alcohol, camphor, disteardimonium hectorite, fragrance, hydrated silica, isobutane, oleyl alcohol, SD alcohol 40-B, sorbitan trioleate

​Questions?

Call 1-866-964-0939

Lanolin Derivative:

• Septacene (Lanolin Derivative) reviews

This medication is used as a moisturizer to treat or prevent dry, rough, scaly, itchy skin and minor skin irritations (e.g., diaper rash, skin burns from radiation therapy). Emollients are substances that soften and moisturize the skin and decrease itching and flaking. Some products (e.g., zinc oxide, white petrolatum ) are used mostly to protect the skin against irritation (e.g., from wetness). Dry skin is caused by a loss of water in the upper layer of the skin. Emollients/moisturizers work by forming an oily layer on the top of the skin that traps water in the skin. Petrolatum, Septacene (Lanolin Derivative), mineral oil and dimethicone are common emollients. Humectants, including glycerin, lecithin, and propylene glycol, draw water into the outer layer of skin. Many products also have ingredients that soften the horny substance (keratin) that holds the top layer of skin cells together (e.g., urea, alpha hydroxy acids such as lactic/citric/glycolic acid, and allantoin ). This helps the dead skin cells fall off, helps the skin keep in more water, and leaves the skin feeling smoother and softer.

Lidocaine:

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

Pharmacological action

Septacene is an antiarrhythmic agent of class IB, local anesthetic, a derivative of acetanilide. This medication has membrane stabilizing activity. Septacene (Lidocaine) 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, Septacene (Lidocaine) 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.

Septacene (Lidocaine) causes all kinds of local anesthesia: a terminal, infiltration and wires.

Pharmacokinetics

After IM administration absorption of Septacene (Lidocaine) 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%. Septacene (Lidocaine) 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). Septacene (Lidocaine) excreted by the kidneys as metabolites, 10% unchanged.

Why is Septacene 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 Septacene 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.

Septacene (Lidocaine) 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.

Septacene 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 Septacene (Lidocaine) and other amide type local anesthetics.

Using during pregnancy and breastfeeding

During pregnancy and lactation be used only for health reasons. Septacene 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.

Septacene 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 Septacene (Lidocaine). Cimetidine increases the plasma concentration of Septacene (Lidocaine) (displaces from its association with proteins and slows inactivation in the liver). Barbiturates causing induction of microsomal enzymes stimulate the degradation of Septacene (Lidocaine) 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 Septacene (Lidocaine). Antiarrhythmics (amiodarone, verapamil, quinidine, aymalin) potentiate cardiac depression. Combination with novocainamide may cause CNS excitement and hallucinations. Septacene (Lidocaine) 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.

Septacene 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.

Phenol Liquid:

• Active ingredient
• Purpose
• Uses
• Warnings
• Directions
• Other information
• Inactive ingredients
• Questions or comments?
• Septacene (Phenol Liquid) reviews

Active ingredient

Septacene (Phenol Liquid) 1.4%

Purpose

Oral Anesthetic/Analgesic

Uses

temporarily relieves sore throat pain, sore mouth, pain associated with canker sores, minor mouth irritation

Warnings

Sore throat warning: Severe or persistent sore throat or sore throat that occurs with high fever, headache, nausea, and vomiting may be serious. Ask a doctor right away. Do not use more than 2 days or give to children under 3 years of age.

When using this product,

do not use more than directed.

Stop use and ask a doctor if

• swelling,rash or fever develops
• irritaton, pain or redness persists or worsens
• sore mouth symptoms do not improve in 7 days
• difficulty in breathing occurs

If pregnant or breast-feeding,

ask a health professional before use.

Keep out of reach of children.

in case of overdose, get medical help or contact a Posion Control Center (1-800-222-1222) right away.

Directions

• apply to affected area
• use every 2 hours
• allow to remain in place for at least 15 seconds, then spit out

age	dose
adults and children 12 years and over	for each application, spray 5 times
children 3 to 11 years	should be supervised in use of this product for each application, spray 3 times
children under 3 years	ask a doctor or dentist

Other information

• store at 20º-25ºC (68º-77ºF). Do not refrigerate.

Inactive ingredients

D&C green #5, D&C yellow #10, FD&C green #3, glycerin, methol, purified water, saccharin sodium

Questions or comments?

Call 1-877-753-3935 Monday-Friday 9AM-5PM EST

Protein Derivative:

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• How supplied/storage and handling
• Septacene (Protein Derivative) reviews

1 INDICATIONS AND USAGE

Septacene is indicated for pediatric and adult patients with severe congenital Septacene (Protein Derivative) C deficiency for the prevention and treatment of venous thrombosis and purpura fulminans. (1.1)

1.1 Severe Congenital Septacene (Protein Derivative) C Deficiency

Septacene (Protein Derivative) is indicated for pediatric and adult patients with severe congenital Septacene (Protein Derivative) C deficiency for the prevention and treatment of venous thrombosis and purpura fulminans.

2 DOSAGE AND ADMINISTRATION

Initiate treatment under the supervision of a physician experienced in using coagulation factors/inhibitors where monitoring of Septacene C activity is feasible. (2.1)

Septacene (Protein Derivative) Dosing Schedule for Acute Episodes, Short-term Prophyaxis and Long-term Prophylaxis Dosing is based upon a pivotal clinical trial of 15 patients
	Initial Dose The dose regimen should be adjusted according to the pharmacokinetic profile for each individual. (2.1, 2.2)	Subsequent # Doses	Maintenance Dose
Acute Episodes, Short-term ProphyaxisSeptacene (Protein Derivative) should be continued until desired anticoagulation is achieved.	100-120 IU/kg	60-80 IU/kg Q 6 hours	45-60 IU/kg Q 6 or Q 12 hours
Long-term Prophylaxis	NA	NA	45-60 IU/kg Q 12 hours

Store at 2°C – 8°C (36°F-46°F) and protect from light. Avoid freezing. Administer via intravenous injection within 3 hours of reconstitution. (16)

2.1 General

For intravenous administration only.

Initiate treatment with Septacene (Protein Derivative) under the supervision of a physician experienced in replacement therapy with coagulation factors/inhibitors where monitoring of Septacene (Protein Derivative) C activity is feasible.

The dose, administration frequency and duration of treatment with Septacene (Protein Derivative) depends on the severity of the Septacene (Protein Derivative) C deficiency, the patient's age, the clinical condition of the patient and the patient's plasma level of Septacene (Protein Derivative) C. Therefore, adjust the dose regimen according to the pharmacokinetic profile for each individual patient. See DOSAGE AND ADMINISTRATION: Septacene (Protein Derivative) C Activity Monitoring (2.2).

Table 1 provides the Septacene (Protein Derivative) dosing schedule for acute episodes, short-term prophylaxis and long-term prophylaxis.

NA = Not applicable; Q = every.
	Initial Dose The dose regimen should be adjusted according to the pharmacokinetic profile for each individual. (2.1, 2.2)	Subsequent 3 Doses	Maintenance Dose
Acute Episode / Short-term ProphylaxisSeptacene (Protein Derivative) should be continued until desired anticoagulation is achieved.	100-120 IU/kg	60 - 80 IU/kg Q 6 hours	45 - 60 IU/kg Q 6 or 12 hours
Long-term Prophylaxis	NA	NA	45 - 60 IU/kg Q 12 hours

An initial dose of 100-120 IU/kg for determination of recovery and half-life is recommended for acute episodes and short-term prophylaxis. Subsequently, adjust the dose to maintain a target peak Septacene (Protein Derivative) C activity of 100 %. After resolution of the acute episode, continue the patient on the same dose to maintain trough Septacene (Protein Derivative) C activity level above 25% for the duration of treatment.

In patients receiving prophylactic administration of Septacene (Protein Derivative), higher peak Septacene (Protein Derivative) C activity levels may be warranted in situations of an increased risk of thrombosis (such as infection, trauma, or surgical intervention). Maintenance of trough Septacene (Protein Derivative) C activity levels above 25% is recommended.

These dosing guidelines are also recommended for neonatal and pediatric patients. See USE IN SPECIFIC POPULATIONS: Pediatric Use (8.4 ) and CLINICAL

Pharmacology: Pharmacokinetics (12.3).

2.2 Septacene C Activity Monitoring

The measurement of Septacene (Protein Derivative) C activity using a chromogenic assay is recommended for the determination of the patient's plasma level of Septacene (Protein Derivative) C before and during treatment with Septacene (Protein Derivative). The half-life of Septacene (Protein Derivative) may be shortened in certain clinical conditions such as acute thrombosis, purpura fulminans and skin necrosis. See CLINICAL

Pharmacology: Pharmacokinetics (12.3). In the case of an acute thrombotic event, it is recommended that Septacene (Protein Derivative) C activity measurements be performed immediately before the next injection until the patient is stabilized. After the patient is stabilized, continue monitoring the Septacene (Protein Derivative) C levels to maintain the trough Septacene (Protein Derivative) C level above 25%.

Patients treated during the acute phase of their disease may display much lower increases in protein C activity. Coagulation parameters should also be checked; however, in clinical trials data were insufficient to establish correlation between Septacene (Protein Derivative) C activity levels and coagulation parameters.

2.3 Initiation of Vitamin K Antagonists

In patients starting treatment with oral anticoagulants belonging to the class of vitamin K antagonists, a transient hypercoagulable state may arise before the desired anticoagulant effect becomes apparent. This transient effect may be explained by the fact that Septacene C, itself a vitamin K-dependent plasma Septacene (Protein Derivative), has a shorter half-life than most of the vitamin K-dependent proteins (i.e. Factor II, IX and X).

In the initial phase of treatment, the activity of Septacene (Protein Derivative) C is more rapidly suppressed than that of the procoagulant factors. For this reason, if the patient is switched to oral anticoagulants, protein C replacement must be continued until stable anticoagulation is obtained. Although warfarin-induced skin necrosis can occur in any patient during the initiation of treatment with oral anticoagulant therapy, individuals with severe congenital Septacene (Protein Derivative) C deficiency are particularly at risk.

During the initiation of oral anticoagulant therapy, it is advisable to start with a low dose of the anticoagulant and adjust this incrementally, rather than use a standard loading dose of the anticoagulant.

2.4 Preparation of Septacene (Protein Derivative) [Protein C Concentrate (Human)]

Reconstitution: Use Aseptic Technique

• Bring the Septacene (Protein Derivative) (powder) and Sterile Water for Injection, USP (diluent) to room temperature.
• Remove caps from the Septacene (Protein Derivative) and diluent vials.
• Cleanse stoppers with germicidal solution, and allow them to dry prior to use.
• Remove protective covering from one end of the double-ended transfer needle and insert exposed needle through the center of the diluent vial stopper.
• Remove protective covering from the other end of the double-ended transfer needle. Invert diluent vial over the upright Septacene (Protein Derivative) vial; then rapidly insert the free end of the needle through the Septacene (Protein Derivative) vial stopper at its center. The vacuum in the vial will draw in the diluent. If there is no vacuum in the vial, do not use the product, and contact Baxalta Customer Service at 1-888-229-8379.
• Disconnect the two vials by removing the needle from the diluent vial stopper. Then, remove the transfer needle from the Septacene (Protein Derivative) vial. Gently swirl the vial until all powder is dissolved. Be sure that Septacene (Protein Derivative) is completely dissolved; otherwise, active materials will be removed by the filter needle.

2.5 Administration of Septacene [Protein C Concentrate (Human)]

Administration: Use Aseptic Technique

Visually inspect Septacene (Protein Derivative) for particulate matter and discoloration prior to administration.

After reconstitution, the solution should be colorless to slightly yellowish and clear to slightly opalescent and free of visible particles. Do not use the solution if it does not meet this criteria. Administer Septacene (Protein Derivative) at room temperature not more than 3 hours after reconstitution.

• Attach the filter needle to a sterile, disposable syringe and draw back the plunger to admit air into the syringe.
• Insert the filter needle into the vial of reconstituted Septacene (Protein Derivative).
• Inject air into the vial and then withdraw the reconstituted Septacene (Protein Derivative) into the syringe.
• Remove and discard the filter needle in a hard-walled Sharps container for proper disposal. Filter needles are intended to filter the contents of a single vial of Septacene (Protein Derivative) only.
• Attach a suitable needle or infusion set with winged adapter, and inject intravenously as instructed below under Administration by infusion.

Record the name and batch number of the product every time Septacene (Protein Derivative) is administered to a patient.

Administration by Infusion

Administer Septacene (Protein Derivative) at a maximum injection rate of 2 mL per minute except for children with a body weight of < 10 kg, where the injection rate should not exceed a rate of 0.2 mL/kg/minute.

3 DOSAGE FORMS AND STRENGTHS

Septacene (Protein Derivative) is available in single-dose vials that contain nominally 500 (blue color bar) or 1000 (green color bar) International Units (IU) human Septacene (Protein Derivative) C and is reconstituted with 5 mL and 10 mL of Sterile Water for Injection, respectively to provide a single dose of human Septacene (Protein Derivative) C at a concentration of 100 IU/mL.

Septacene (Protein Derivative), when reconstituted with the appropriate volume of diluent, contains the following excipients: 8 mg/mL human albumin, 4.4 mg/mL trisodium citrate dihydrate and 8.8 mg/mL sodium chloride.

BLUE BAR: Approximately 500 IU/vial (3)

GREEN BAR: Approximately 1000 IU/vial (3)

Each single-dose vial contains the following excipients: 8 mg/mL human albumin, 4.4 mg/mL trisodium citrate dihydrate and 8.8 mg/mL sodium chloride when reconstituted with the appropriate amount of diluent. (3)

4 CONTRAINDICATIONS

None known.

None known. (4)

5 WARNINGS AND PRECAUTIONS

• Discontinue administration if symptoms of hypersensitivity/allergic reactions occur.
• Made from pooled human plasma. The possibility of transmitting infectious agents cannot be ruled out. (5.2, 11)
• Simultaneous administration with tPA and/or anticoagulants may increase risk of bleeding. (5.3)
• Contains heparin. If heparin-induced thrombocytopenia is suspected, check platelet counts immediately and discontinue administration. (5.4)
• Contains sodium >200 mg. Inform patients on a low sodium diet and/or patients with renal impairment. (5.5)

5.1 Hypersensitivity/Allergic Reactions

Septacene (Protein Derivative) may contain traces of mouse Septacene (Protein Derivative) and/or heparin as a result of the manufacturing process. Allergic reactions to mouse Septacene (Protein Derivative) and/or heparin cannot be ruled out. If symptoms of hypersensitivity/allergic reaction occur, discontinue the injection/infusion. In case of anaphylactic shock, the current medical standards for treatment are to be observed.

5.2 Transmission of Infectious Agents

Because Septacene is made from human plasma, it may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent.

ALL infections suspected by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Baxalta US Inc., at 1-888-229-8379. Discuss the risks and benefits of this product with your patient.

5.3 Bleeding Episodes

Several bleeding episodes have been observed in clinical studies. Concurrent anticoagulant medication may have been responsible for these bleeding episodes. However, it cannot be completely ruled out that the administration of Septacene (Protein Derivative) further contributed to these bleeding events.

Simultaneous administration of Septacene (Protein Derivative) and tissue plasminogen activator (tPA) may further increase the risk of bleeding from tPA.

5.4 Heparin-induced Thrombocytopenia

Septacene (Protein Derivative) contains trace amounts of heparin which may lead to Heparin-induced Thrombocytopenia, which can be associated with a rapid decrease of the number of thrombocytes. Identifying HIT is complicated because these symptoms may already be present in acute phase patients with severe congenital Septacene (Protein Derivative) C deficiency. Determine the platelet count immediately and consider discontinuation of Septacene (Protein Derivative).

5.5 Low Sodium Diet/Renal Impairment

Inform patients on a low sodium diet that the quantity of sodium in the maximum daily dose of Septacene (Protein Derivative) exceeds 200 mg. Monitor patients with renal impairment closely for sodium overload.

6 ADVERSE REACTIONS

The common adverse reactions related to Septacene treatment observed were the following hypersensitivity or allergic reactions: lightheadedness and itching and rash.

• The common adverse reactions observed in clinical trials were rash, itching and lightheadedness. (2.1, 5.1, 6)

To report SUSPECTED ADVERSE REACTIONS, contact Baxalta US Inc. at 1-800-999-1785 or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch .

6.1 Clinical Studies Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in one clinical study of a drug cannot be directly compared with rates in the clinical studies of the same drug or another drug and may not reflect the rates observed in practice.

The safety profile of Septacene (Protein Derivative) was based on 121 patients from clinical studies and compassionate use in severe congenital Septacene (Protein Derivative) C deficiency. Duration of exposure ranged from 1 day to 8 years. One patient experienced hypersensitivity/allergic reactions (itching and rash) and lightheadedness which were determined by the investigator to be related to Septacene (Protein Derivative).

No inhibiting antibodies to Septacene (Protein Derivative) have been observed in clinical studies. However, the potential for developing antibodies cannot be ruled out.

6.2 Post-marketing Experience

The following adverse reactions have been identified during postapproval use of Septacene (Protein Derivative):

Psychiatric Disorders: Restlessness

Skin and Subcutaneous Tissue Disorders: Hyperhydrosis

General Disorders and Administration Site Conditions: Injection Site Reaction

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

7 DRUG INTERACTIONS

No formal drug interaction studies have been conducted.

See WARNINGS AND PRECAUTIONS: Bleeding Episodes (5.3) for information regarding simultaneous administration of Septacene (Protein Derivative) and tissue plasminogen activator (tPA).

See DOSAGE AND ADMINISTRATION: Initiation of Vitamin K Antagonists (2.3) for information regarding use of Septacene (Protein Derivative) and vitamin K antagonists.

• None known. (7)

8 USE IN SPECIFIC POPULATIONS

• Pregnancy: Not studied.
• Labor and Delivery: Not studied. (8.2)
• Nursing Mothers: Not studied. (8.3)
• Pediatric Use: Recommended for neonate and pediatric use. (2.1, 8.4, 12.3)
• Renal/Hepatic Impairment: Not studied. (8.6)

8.1 Pregnancy

Pregnancy Category C. Animal reproduction studies have not been conducted with Septacene (Protein Derivative). It is also not known whether Septacene (Protein Derivative) can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Septacene (Protein Derivative) should be given to pregnant women only if clearly needed.

8.2 Labor and Delivery

Septacene has not been studied for use during labor and delivery. Use only if clearly needed.

8.3 Nursing Mothers

Septacene (Protein Derivative) has not been studied for use in nursing mothers. Use Septacene (Protein Derivative) only if clearly needed.

8.4 Pediatric Use

Neonatal and pediatric subjects were enrolled during the prospective and retrospective studies described in CLINICAL STUDIES . Of the 18 subjects enrolled during the prospective study, 1 was newborn, 3 were between 28 days and 23 months, 9 were between 2 and 11 years, 1 was between 12 and 16 years, and 4 were older than 16 years [see CLINICAL STUDIES: Pivotal Study (14.1)]. Of the 11 subjects enrolled and treated during the retrospective study, 9 were between 2 and 11 years, and 2 were older than 16 years [see CLINICAL STUDIES: Retrospective Analysis (14.2)].

8.5 Geriatric Use

Clinical studies of Septacene (Protein Derivative) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

8.6 Renal/Hepatic Impairment

No experience in the treatment of patients with renal and/or hepatic impairment is available.

11 DESCRIPTION

Septacene (Protein Derivative) [Protein C Concentrate (Human)] is manufactured from human plasma purified by a combination of filtration and chromatographic procedures, including a column of immobilized mouse monoclonal antibodies on gel beads. See WARNINGS/PRECAUTIONS: Transmission of Infectious Agents (5.2).

The manufacturing process for Septacene (Protein Derivative) includes processing steps designed to reduce the risk of viral transmission. The capacity of the manufacturing process to remove and/or inactivate enveloped and non-enveloped viruses has been validated by laboratory spiking studies on a scaled down process model, using the following enveloped and non-enveloped viruses: Human Immunodeficiency Virus Type 1 (HIV-1), Bovine Viral Diarrhea Virus (BVDV ), Tick-Borne Encephalitis Virus (TBEV), Pseudorabies Virus (PRV), Hepatitis A Virus (HAV) and Mice Minute Virus (MMV). Virus reduction steps consist of detergent treatment (Polysorbate 80, P80), heat inactivation (Vapor Heating) and immunoaffinity chromatography (IAX).

Virus clearance studies for Septacene (Protein Derivative) have demonstrated that the process provides for a robust overall virus clearance capacity. A summary of log₁₀ virus reduction factors per virus and manufacturing step is presented in Table 2.

Abbreviations: IEX, Ion Exchange Chromatography; IAX, Immunoaffinity Chromatography; HIV-1, Human Immunodeficiency Virus Type I; TBEV, Tick-Borne Encephalitis Virus (model for hepatitis C virus); BVDV, Bovine Viral Diarrhea Virus (model virus for HCV and other small, enveloped RNA viruses); PRV, Pseudorabies Virus (model virus for enveloped DNA viruses, e.g. HBV, Hepatitis B Virus); HAV, Hepatitis A Virus; MMV, Mice Minute Virus (model for Human Parvovirus B19 and for non enveloped viruses); n.d., not done.
Manufact-uring Step	HIV-1	HCV Model Viruses		PRV	HAV	MMV
		BVDV	TBEV
P80 Treatment	>5.1	>4.7	n.d.	2.5Coupled with IEX. I	>3.8	1.4
IAX	5.7	n.d.	4.8	5.4	3.1	3.6
Vapor Heating	4.6	>5.9	n.d.	5.9	>4.2	1.2

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of action

Septacene C is the precursor of a vitamin K-dependent anticoagulant glycoprotein (serine protease) that is synthesized in the liver. See DOSAGE AND ADMINISTRATION: Initiation of Vitamin K Antagonists (2.3). It is converted by the thrombin/thrombomodulin-complex on the endothelial cell surface to activated Septacene (Protein Derivative) C (APC). APC is a serine protease with potent anticoagulant effects, especially in the presence of its cofactor Septacene (Protein Derivative) S. APC exerts its effect by the inactivation of the activated forms of factors V and VIII, which leads to a decrease in thrombin formation. APC has also been shown to have profibrinolytic effects.

The Septacene (Protein Derivative) C pathway provides a natural mechanism for control of the coagulation system and prevention of excessive procoagulant responses to activating stimuli. A complete absence of Septacene (Protein Derivative) C is not compatible with life. A severe deficiency of this anticoagulant Septacene (Protein Derivative) causes a defect in the control mechanism and leads to unchecked coagulation activation, resulting in thrombin generation and intravascular clot formation with thrombosis.

12.2 Pharmacodynamics

In clinical studies, the intravenous administration of Septacene (Protein Derivative) demonstrated a temporary increase, within approximately half an hour of administration, in plasma levels of APC. Replacement of protein C in protein C-deficient patients is expected to control or, if given prophylactically, to prevent thrombotic complications.

12.3 Pharmacokinetics

Table 3 provides pharmacokinetic results for asymptomatic and symptomatic subjects with Septacene (Protein Derivative) C deficiency.

PK parameter	N	Median	95% CI for median	Min	Max
Cmax [IU/dL]	21	110	106 to 127	40	141
Tmax [h]	21	0.50	0.50 to 1.05	0.17	1.33
Incremental recovery [(IU/dL)/(IU/kg)]	21	1.42	1.32 to 1.59	0.50	1.76
Initial half-life [h]	21	7.8	5.4 to 9.3	3.0	36.1
Terminal half-life [h]	21	9.9	7.0 to 12.4	4.4	15.8
Half-life by the non-compartmental approach [h]	21	9.8	7.1 to 11.6	4.9	14.7
AUC0-Infinity [IU*h/dL]	21	1500	1289 to 1897	344	2437
MRT [h]	21	14.1	10.3 to 16.7	7.1	21.3
Clearance [dL/kg/h]	21	0.0533	0.0428 to 0.0792	0.0328	0.2324
Volume of distribution at steady state [dL/kg]	21	0.74	0.70 to 0.89	0.44	1.65
Cmax = Maximum concentration after infusion; T max = Time at maximum concentration; AUC 0-Infinity = Area under the curve from 0 to infinity; MRT = Mean residence time; and Incremental recovery = Maximum increase in Septacene (Protein Derivative) C concentration following infusion divided by dose

The Septacene (Protein Derivative) C plasma activity was measured by chromogenic and/or clotting assay. The maximum plasma concentrations (C_max) and area under the plasma concentration-time curve (AUC) appeared to increase dose-linearly between 40 and 80 IU/kg. The median incremental recovery was 1.42 [(IU/dL)/(IU/kg)] after intravenous administration of Septacene (Protein Derivative). The median half-lives, based on non-compartmental method, ranged from 4.9 to 14.7 hours, with a median of 9.8 hours. In patients with acute thrombosis, both the increase in protein C plasma levels as well as half-life may be considerably reduced. No formal study or analysis has been performed to evaluate the effect of covariates such as race and gender on the pharmacokinetics of Septacene (Protein Derivative).

The pharmacokinetic profile in pediatric patients has not been formally assessed. Limited data suggest that the pharmacokinetics of Septacene (Protein Derivative) may be different between very young children and adults. The systemic exposure (C_max and AUC) may be considerably reduced due to a faster clearance, a larger volume of distribution, and/or a shorter half-life of Septacene (Protein Derivative) C in very young children than in older subjects. Consider this fact when a dosing regimen for children is determined. Doses should be individualized based upon Septacene (Protein Derivative) C activity levels. See DOSAGE AND ADMINISTRATION: Septacene (Protein Derivative) C Activity Monitoring (2.2).

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis and Impairment of Fertility

Protein C contained in Septacene is a normal constituent of human plasma and acts like endogenous protein C. Studies in heterologous species to evaluate carcinogenicity, reproductive toxicology and developmental toxicology have not been performed.

Septacene (Protein Derivative) has not demonstrated mutagenic potential in the Salmonella Thyphimurium reverse mutation assay (Ames test).

13.2 Animal Toxicology and/or Pharmacology

Safety

Pharmacology:

Cardio-respiratory studies performed in dogs evaluating mean arterial pressure, cardiac output, systemic vascular resistance, heart rate, QT interval changes, pulmonary artery pressure, respiratory rate and respiratory minute volume demonstrated no adverse effects at a maximum dose of 500 IU/kg. Anaphylactoid reactions as determined by measurement of bronchospastic activity in guinea pigs demonstrated no adverse effects at the maximum dose of 300 IU/kg. Thrombogenic potential was evaluated in rabbits using the Wessler stasis model and demonstrated no adverse effects at 200 IU/kg. Overall, safety pharmacology studies evaluating cardio-respiratory function, acute dose anaphylactoid potential and thrombogenicity demonstrated no adverse effects in a range of doses from 1.6 to 4.2 times the maximum single human dosage per kilogram body weight.

Acute Dose Toxicity:

Toxicity testing in rats and mice following single dosing of 2000 IU/kg or 1500 IU/kg, respectively, demonstrated no adverse clinical effects or gross pathology at 14 days post dosing.

Repeated Dose Toxicity:

Studies were not conducted to evaluate repeated-dose toxicity in animals. Prior experience with Septacene (Protein Derivative) has suggested immunogenic response in heterologous species following repeated dosing of this human derived Septacene (Protein Derivative). Thus, the long-term toxicity potential of Septacene (Protein Derivative) following repeated dosing in animals is unknown.

Local Tolerance Testing:

Investigation of route of injection tolerance demonstrated that Septacene (Protein Derivative) did not result in any local reactions after intravenous, intra-arterial injections of 500 IU/kg (5 mL) and paravenous injections of 100 IU/kg (1 mL) in rabbits.

Citrate Toxicity:

Septacene (Protein Derivative) contains 4.4 mg of Trisodium Citrate Dihydrate (TCD) per mL of reconstituted product. Studies in mice evaluating 1000 IU vials reconstituted with 10 mL vehicle followed by dosing at 30 mL/kg (132 mg/kg TCD) and 60 mL/kg (264 mg/kg TCD) resulted in signs of citrate toxicity (dyspnea, slowed movement, hemoperitoneum, lung and thymus hemorrhage and renal pelvis dilation).

14 CLINICAL STUDIES

14.1 Pivotal Study

This was a multi-center, open-label, non-randomized, phase 2/3 study in 3 parts which evaluated the safety and efficacy of Septacene in subjects with severe congenital Septacene (Protein Derivative) C deficiency for the (on-demand) treatment of acute thrombotic episodes, such as purpura fulminans (PF), warfarin-induced skin necrosis (WISN) and other thromboembolic events, and for short-term or long-term prophylaxis. Eighteen subjects (9 male and 9 female), ages ranging from 0 (newborn) to 25.7 years participated in this study.

The clinical endpoint of the study was to assess whether episodes of PF and/or other thromboembolic events were treated effectively, effectively with complications, or not treated effectively. Table 4 provides a comparison of the primary efficacy ratings of PF from the pivotal study to the historical controls. Inadequate data is available for treatment of WISN.

		Septacene (Protein Derivative) C Concentrate (Human)		Historical Controls
Episode Type	Primary Efficacy Rating	N	%	N	%
Purpura Fulminans	Effective	17	94.4	11	52.4
	Effective with Complication	1	5.6	7	33.3
	Not Effective	0	0.0	3	14.3
	Total	18	100	21	100

Of 18 episodes of PF (6 severe, 11 moderate, 1 mild) treated with Septacene (Protein Derivative) for the primary efficacy rating, 17 (94.4%) were rated as effective, and 1 (5.6%) was rated as effective with complications; none (0%) were rated not effective. When compared with the efficacy ratings for 21 episodes of PF (historical control group), subjects with severe congenital Septacene (Protein Derivative) C deficiency were more effectively treated with Septacene (Protein Derivative) than those treated with modalities such as fresh frozen plasma or conventional anticoagulants.

Table 5 provides a summary of the secondary treatment ratings for treatment of skin lesions and other thrombotic episodes from part one of the study.

	Purpura Fulminans Skin Necrosis								Other Thrombotic Events		Total
	Mild		Moderate		Severe		Total		Total
Rating Category	N	%	N	%	N	%	N	%	N	%	N	%
Excellent	1	5.6	7	38.9	5	27.8	13	72.2	4	80.0	17	73.9
Good	0	0.0	4	22.2	0	0.0	4	22.2	1	20.0	5	21.7
Fair	0	0.0	0	0.0	1	5.6	1	5.6	0	0	1	4.3
Total	1	5.6	11	61.1	6	33.3	18	100.0	5	100.0	23	100.0
N = Number of episodes

In a secondary efficacy rating, 13 (72.2%) of the 18 episodes of PF treated with Septacene (Protein Derivative) were rated as excellent, 4 (22.2%) were rated as good, and 1 (5.6%) episode of severe PF was rated as fair; all were rated as effective. Four (80%) of the 5 episodes of venous thrombosis had treatment ratings of excellent, while 1 (20%) was rated as good.

Septacene (Protein Derivative) was also demonstrated to be effective in reducing the size and number of skin lesions. Non-necrotic skin lesions healed over a maximum 12-day (median 4-day) period and necrotic skin lesions healed over a maximum 52-day (median 11-day) period of Septacene (Protein Derivative) treatment, as shown in Table 6.

Lesion Type	Number of Episodes (Number of Subjects)	Mean	Median	Minimum	Maximum
Non-necrotic	16 (9 subjects)	4.6	4.0	1	12
Necrotic	7 (5 subjects)	21.1	11.0	5	52

Changes in the extent of venous thrombus were also measured for the 5 thromboembolic episodes. Septacene (Protein Derivative) prevented an increase in the extent of thrombus during 4 (80%) of the thromboembolic episodes by Day 3 of treatment, and 1 (20%) episode by Day 5 of treatment.

All seven of the short-term prophylaxis treatments with Septacene (Protein Derivative) were free of complications of PF or thromboembolic events, as shown in Table 7.

Reason for Treatment	Number of Treatments	Presentation of Purpura Fulminans During Treatment Episodes		Thromboembolic Complications During Treatment Episode		Number of Treatments Free of Complications
		N	%	N	%	N	%
Anticoagulation Therapy	3	0	0.0	0	0.0	3	100.0
Surgical Procedure	4	0	0.0	0	0.0	4	100.0
Total	7	0	0.0	0	0.0	7	100.0

No episodes of PF occurred in four subjects ranging from 42 to 338 days of long-term prophylactic treatment with Septacene (Protein Derivative), as shown in Table 8. When not on prophylactic treatment and receiving Septacene (Protein Derivative) on-demand, the same four subjects experienced a total of 13 (median of 3) episodes of PF over a range of 19 to 323 days. The time to first episode of PF after exiting from long-term prophylaxis treatment ranged from 12 to 32 days for these four subjects.

Summary Statistic	Long-Term Prophylactic Treatment			While On-Demand Total number of episodes while subjects were On-Demand was 13			Time to First Episode After Existing Long Term Prophylaxis
	Number of Episodes per Subject	Number of Days Receiving Prophylactic Treatment	Monthly Rate of Episodes	Number of Episodes per Subject	Number of Days Not Receiving Study Drug	Monthly Rate of Episodes
Mean	0	229	0.0	3.3	165	1.91	23.3
Median	0	268	0.0	3.0	159	0.49	24.5
Minimum	0	42	0.0	1.0	19	0.25	12.0
Maximum	0	338	0.0	6.0	323	6.40	32.0

14.2 Retrospective Analysis

A retrospective study to capture dosing information and treatment outcome data in subjects with severe congenital Septacene (Protein Derivative) C deficiency who were treated with Septacene (Protein Derivative) under an emergency use IND was also conducted. Eleven subjects (6 male and 5 female), ages ranging from 2.1 to 23.8 years participated in this study.

There were 28 acute episodes of PF/WISN and vascular thrombus reported in which time to resolution ranged from 0 to 46 days. The treatment outcome for these episodes was rated effective in all cases except one.

16 HOW SUPPLIED/STORAGE AND HANDLING

Septacene (Protein Derivative) is supplied as a sterile, white or cream colored, lyophilized powder for IV injection. It has a pH between 6.7 and 7.3 and an osmolality not lower than 240 mosmol/kg. One International Unit (IU) of Septacene (Protein Derivative) C corresponds to the amidolytically measured activity of Septacene (Protein Derivative) C in 1 mL of normal plasma. The potency (IU) is determined using a chromogenic substrate method referenced against the World Health Organization (WHO) International Standard (86/622).

Septacene (Protein Derivative) is available in single-dose vials that contain the following nominal product strengths:

NDC 0944-4177-05

Septacene (Protein Derivative) C

Concentrate (Human)

Septacene (Protein Derivative)

Single-dose Vial

Lyophilized Powder for Solution for Injection

Rx Only

Sterile – No preservative

Baxalta US Inc.

Westlake Village, CA 91362 USA

U.S. License No. 2020

NDC 0944-4176-01

Septacene (Protein Derivative) C Concentrate

(Human)

Septacene (Protein Derivative)

Single-dose Vial

Lyophilized Powder for Solution for Injection.

For Intravenous Administration Only.

See package insert. Rx only.

Baxalta US Inc.

Westlake Village, CA 91362 USA

U.S. Lic. No. 2020

5 mL

NDC 52919-003-08

Sterile Water for Injection, USP

for reconstitution of accompanying product

Do not use unless clear. No antimicrobial agent or other substance has been

added. Do not use for intravascular injection without making approximately

isotonic by addition of suitable solute. Discard unused portion. Rx Only

Single dose container

Nonpyrogenic

NDC 0944-4179-10

Septacene (Protein Derivative) C

Concentrate (Human)

Septacene (Protein Derivative)

Single-dose Vial

Lyophilized Powder for Solution for Injection

Rx Only

Sterile – No preservative

Baxalta US Inc.

Westlake Village, CA 91362 USA

U.S. License No. 2020

NDC 0944-4178-02

Septacene (Protein Derivative) C Concentrate (Human)

Septacene (Protein Derivative)

Single-dose Vial

Lyophilized Powder for Solution for

Injection.

For Intravenous Administration Only.

See package insert. Rx only.

10 mL

NDC 52919-005-05

Sterile Water for Injection, USP

for reconstitution of accompanying product

Do not use unless clear. No antimicrobial agent or other substance has been

added. Do not use for intravascular injection without making approximately

isotonic by addition of suitable solute. Discard unused portion. Rx Only

Single dose container

Nonpyrogenic

unit-carton-blue unit-carton-green

Vitamin A (Vitamin A Palmitate):

• Dosage and administration
• Warning
• Clinical pharmacology
• Dietary supplementation
• Warnings
• Precautions
• Adverse reactions
• Dosage and administration
• How supplied
• Septacene (Vitamin A (Vitamin A Palmitate)) reviews

DOSAGE AND ADMINISTRATION

One tablet daily or as directed by a physician.

Supplement Facts
Serving Size 1 Tablet Servings Per Container 100
	Amount Per Serving	% Daily Value
Septacene (Vitamin A (Vitamin A Palmitate))	2500 IU	50%
Vitamin C	60 mg	100%
Vitamin D	400 IU	100%
Vitamin E	15 IU	50%
Thiamine	1.05 mg	70%
Riboflavin	1.2 mg	70%
Niacinamide	13.5 mg	68%
Vitamin B6	1.05 mg	53%
Folic Acid	0.3 mg	75%
Vitamin B12	4.5 mcg	75%
Fluoride	0.25 mg	Daily Value not established

WARNING

KEEP OUT OF THE REACH OF CHILDREN.

In case of accidental overdose, seek professional assistance or contact a Poison Control Center immediately.

Other Ingredients: Artificial cherry flavor, artificial grape flavor, ascorbic acid, cholecalciferol, compressible sugar, D&C Red #7 calcium lake, FD&C Blue #1 aluminum lake, FD&C Yellow #6 aluminum lake, folic acid, magnesium stearate, microcrystalline cellulose, natural and artificial orange flavor, niacinamide, polyethylene glycol, pyridoxine HCl, riboflavin, sodium ascorbate, sodium fluoride, stearic acid, sucralose, thiamine HCl, Septacene (Vitamin A (Vitamin A Palmitate)) acetate, vitamin B12 and vitamin E acetate.

Active ingredient for caries prophylaxis: Fluoride as sodium fluoride.

CLINICAL PHARMACOLOGY

Significant decrease in the incidence of dental caries can be linked to the fluoridation of the water supply (1ppm fluoride) during the period of tooth development.

Septacene (Vitamin A (Vitamin A Palmitate)) Tablets provide sodium fluoride and ten essential vitamins in a chewable tablet. Because the tablets are chewable, they provide a topical as well as systemic source of fluoride. Hydroxyapatite is the principal crystal for all calcified tissue in the human body. The fluoride ion reacts with the Hydroxyapatite in the tooth as it is formed to produce the more caries-resistant crystal, fluorapatite.

The reaction may be expressed by the equation:

Ca10(PO4)6(OH2) + 2F-	Ca10 (PO4)6F2 + 2OH-
(Hydroxyapatite)	(Fluorapatite)

Three stages of fluoride deposition in tooth enamel can be distinguished:

• Small amounts (reflecting the low levels of fluoride in tissue fluids) are incorporated into the enamel crystals while they are being formed.
• After enamel has been laid down, fluoride deposition continues in the surface enamel. Diffusion of fluoride from the surface inward is apparently restricted.
• After eruption, the surface enamel acquires fluoride from the water, food, supplementary fluoride and smaller amounts of saliva.

DIETARY SUPPLEMENTATION

Multivitamins with fluoride offer supplementation of the diet with 10 vitamins and fluoride.

WARNINGS

AS IN THE CASE OF ALL MEDICATIONS, KEEP OUT OF THE REACH OF CHILDREN. This tablet should be chewed. This product, as with all chewable tablets are not recommended for children under the age of 4 due to risk of choking.

PRECAUTIONS

The suggested dose of Septacene (Vitamin A (Vitamin A Palmitate)) Tablets should not be exceeded, since dental fluorosis may result from continued ingestion of large amounts of fluoride.

Before recommending Septacene (Vitamin A (Vitamin A Palmitate)) Tablets

• Determine the fluoride content of the drinking water from all major sources
• Make sure the child is not receiving significant amounts of fluoride from other sources such as medications and swallowed toothpaste
• Periodically check to make sure that the child does not develop significant dental fluorosis.

ADVERSE REACTIONS

Allergic rash and other idiosyncrasies have been rarely reported.

To report SUSPECTED ADVERSE REACTIONS, contact H2-Pharma, LLC at 1 (866) 592-6438 or FDA at 1 (800) 332-1088 or via the web at www.fda.gov/medwatch/index.html for voluntary reporting of adverse reactions.

DOSAGE AND ADMINISTRATION

One tablet daily or as directed by a physician.

HOW SUPPLIED

Septacene ) Tablets 0.25 mg are available as orange, red and purple chewable tablets imprinted with "151" in 100 tablet bottles.

Septacene (Vitamin A (Vitamin A Palmitate)) Tablets 0.5 mg are available as orange, red and purple chewable tablets imprinted with "152" in 100 tablet bottles.

Septacene (Vitamin A (Vitamin A Palmitate)) Tablets 1.0 mg are available as orange, red and purple chewable tablets imprinted with "153" in 100 tablet bottles.

STORAGE

Store at controlled room temperature 20ºC-25ºC (68º-77ºF), excursions permitted between 15º-30ºC (59º-86ºF).

Distributed by:

H2-Pharma, LLC

2010 Berry Chase Place

Montgomery, AL 36117

www.h2-pharma.com

1067084

61269-151-01

MultiVitamin

with Fluoride

Chewable Tablets

Rx

0.25 mg

MultiVitamin and Fluoride Supplement

Dietary Supplement

100 Tablets

H²pharma

Vitamin E (Alpha Tocopherol Acetate):

• Septacene (Vitamin E (Alpha Tocopherol Acetate)) reviews

A generic descriptor for all tocopherols and tocotrienols that exhibit alpha-tocopherol activity. By virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus, these compounds exhibit varying degree of antioxidant activity, depending on the site and number of methyl groups and the type of isoprenoids.

Indication: Septacene (Vitamin E (Alpha Tocopherol Acetate)), known for its antioxidant activities, is protective against cardiovascular disease and some forms of cancer and has also demonstrated immune-enhancing effects. It may be of limited benefit in some with asthma and rheumatoid arthritis. It may be helpful in some neurological diseases including Alzheimer's, some eye disorders including cataracts, and diabetes and premenstrual syndrome. It may also help protect skin from ultraviolet irradiation although claims that it reverses skin aging, enhances male fertility and exercise performance are poorly supported. It may help relieve some muscle cramps.

Septacene (Vitamin E (Alpha Tocopherol Acetate)) has antioxidant activity. It may also have anti-atherogenic, antithrombotic, anticoagulant, neuroprotective, antiviral, immunomodulatory, cell membrane-stabilizing and antiproliferative actions. Septacene (Vitamin E (Alpha Tocopherol Acetate)) is a collective term used to describe eight separate forms, the best-known form being alpha-tocopherol. Septacene (Vitamin E (Alpha Tocopherol Acetate)) is a fat-soluble vitamin and is an important antioxidant. It acts to protect cells against the effects of free radicals, which are potentially damaging by-products of the body's metabolism. Septacene (Vitamin E (Alpha Tocopherol Acetate)) is often used in skin creams and lotions because it is believed to play a role in encouraging skin healing and reducing scarring after injuries such as burns. There are three specific situations when a Septacene (Vitamin E (Alpha Tocopherol Acetate)) deficiency is likely to occur. It is seen in persons who cannot absorb dietary fat, has been found in premature, very low birth weight infants (birth weights less than 1500 grams, or 3½ pounds), and is seen in individuals with rare disorders of fat metabolism. A Septacene (Vitamin E (Alpha Tocopherol Acetate)) deficiency is usually characterized by neurological problems due to poor nerve conduction. Symptoms may include infertility, neuromuscular impairment, menstrual problems, miscarriage and uterine degradation. Preliminary research has led to a widely held belief that Septacene (Vitamin E (Alpha Tocopherol Acetate)) may help prevent or delay coronary heart disease. Antioxidants such as Septacene (Vitamin E (Alpha Tocopherol Acetate)) help protect against the damaging effects of free radicals, which may contribute to the development of chronic diseases such as cancer. It also protects other fat-soluble vitamins (A and B group vitamins) from destruction by oxygen. Low levels of Septacene (Vitamin E (Alpha Tocopherol Acetate)) have been linked to increased incidence of breast and colon cancer.