Prescription Drugs

CLINICAL PHARMACOLOGY Pentothal Pentothal (Thiopental Sodium for Injection, USP) is an ultrashort-acting depressant of the central nervous system which induces hypnosis and anesthesia, but not analgesia. It produces hypnosis within 30 to 40 seconds of intravenous injection. Recovery after a small dose is rapid, with some somnolence and retrograde amnesia. Repeated intravenous doses lead to prolonged anesthesia because fatty tissues act as a reservoir; they accumulate Pentothal (thiopental sodium) in concentrations 6 to 12 times greater than the plasma concentration, and then release the drug slowly to cause prolonged anesthesia. The half-life of the elimination phase after a single intravenous dose is three to eight hours. The distribution and fate of Pentothal (thiopental sodium) (as with other barbiturates) is influenced chiefly by its lipid solubility (partition coefficient), protein binding and extent of ionization. Pentothal (thiopental sodium) has a partition coefficient of 580. Approximately 80% of the drug in the blood is bound to plasma protein. Pentothal (thiopental sodium) is largely degraded in the liver and to a smaller extent in other tissues, especially the kidney and brain. It has a pKa of 7.4. Concentration in spinal fluid is slightly less than in the plasma. Biotransformation products of thiopental are pharmacologically inactive and mostly excreted in the urine. Diluents in Pentothal (thiopental sodium) ® Kits Ready-To-Mix Syringes and Vials (For preparing solutions of Thiopental Sodium for Injection, USP) Sterile Water for Injection, USP serves only as a pharmaceutic aid for diluting or dissolving drugs prior to administration. Water is an essential constituent of all body tissues and accounts for approximately 70% of total body weight. Average normal adult daily requirement ranges from two to three liters (1.0 to 1.5 liters each for insensible water loss by perspiration and urine excretion). Water balance is maintained by various regulatory mechanisms. Water distribution depends primarily on the concentration of dissociated electrolytes in the body compartments and sodium (Na+) plays a major role in maintaining a physiologic equilibrium between fluid intake and output. 0.9% Sodium Chloride Injection, USP serves only as an isotonic vehicle for drugs prior to administration. Sodium chloride in water is an electrolyte solution of sodium (Na+) and chloride (Cl-) ions. These ions are normal constituents of the body fluids (principally extracellular) and are essential for maintaining electrolyte balance. The distribution and excretion of sodium (Na+) and chloride (Cl-) are largely under the control of the kidney which maintains a balance between intake and output of these ions. The small volumes of fluid and amounts of sodium chloride provided by 0.9% Sodium Chloride Injection in Ready-to-Mix Syringes are unlikely to produce a significant effect on fluid or electrolyte balance.

Pentothal (thiopental sodium) for Injection, USP DESCRIPTION WARNING: MAY BE HABIT FORMING. Pentothal (Thiopental Sodium for Injection, USP) is a thiobarbiturate, the sulfur analogue of sodium pentobarbital. The drug is prepared as a sterile powder and after reconstitution with an appropriate diluent is administered by the intravenous route. Pentothal (thiopental sodium) is chemically designated sodium 5-ethyl-5-(1-methylbutyl)-2-thiobarbiturate. The drug is a yellowish, hygroscopic powder, stabilized with anhydrous sodium carbonate as a buffer (60 mg/g of thiopental sodium). Diluents in Pentothal (thiopental sodium) ® Kits Ready-To-Mix Syringes and Vials (For preparing solutions of Thiopental Sodium for Injection, USP) The following diluents in various container, syringe and vial sizes are provided in Pentothal (thiopental sodium) Kits, Pentothal (thiopental sodium) Ready-to-Mix Syringes and Vials for preparing solutions of Pentothal (Thiopental Sodium for Injection, USP) for clinical use: Sterile Water for Injection, USP is a sterile, nonpyrogenic preparation of water for injection which contains no bacteriostat, antimicrobial agents or added buffers. The pH is 5.7 (5.0 to 7.0). Sterile Water for Injection, USP is a pharmaceutic aid (solvent) for intravenous administration only after addition of a solute. Water is chemically designated H2O. 0.9% Sodium Chloride Injection, USP is a sterile, nonpyrogenic, isotonic solution of sodium chloride and water for injection. Each mL contains sodium chloride 9 mg (308 mOsmol/liter calc). It contains no bacteriostat, antimicrobial agents or added buffers except for pH adjustment. May contain hydrochloric acid and/or sodium hydroxide for pH adjustment. pH is 5.7 (4.5 to 7.0). 0.9% Sodium Chloride Injection, USP is an isotonic vehicle for intravenous administration of another solute. Sodium chloride is chemically designated NaCl, a white crystalline compound freely soluble in water. The semi-rigid vial contained in List Nos. 3329, 6418, 6419, 6420 and 6435 is fabricated from a specially formulated polyolefin. It is a copolymer of ethylene and propylene. The safety of the plastic has been confirmed by tests in animals according to USP biological standards for plastic containers. The container requires no vapor barrier to maintain the proper labeled volume.

PATIENT INFORMATION See WARNINGS, PRECAUTIONS and CONTRAINDICATIONS.

OVERDOSE Pentothal (thiopental sodium) Overdosage may occur from too rapid or repeated injections. Too rapid injection may be followed by an alarming fall in blood pressure even to shock levels. Apnea, occasional laryngospasm, coughing and other respiratory difficulties with excessive or too rapid injections may occur. In the event of suspected or apparent overdosage, the drug should be discontinued, a patent airway established (intubate if necessary) or maintained, and oxygen should be administered, with assisted ventilation if necessary. The lethal dose of barbiturates varies and cannot be stated with certainty. Lethal blood levels may be as low as 1 mg/100 mL for short-acting barbiturates; less if other depressant drugs or alcohol are also present. MANAGEMENT OF 0VERDOSAGE It is generally agreed that respiratory depression or arrest due to unusual sensitivity to thiopental sodium or overdosage is easily managed if there is no concomitant respiratory obstruction. If the airway is patent, any method of ventilating the lungs (that prevents hypoxia) should be successful in maintaining other vital functions. Since depression of respiratory activity is one of the characteristic actions of the drug, it is important to observe respiration closely. Should laryngeal spasm occur, it may be relieved by one of the usual methods, such as the use of a relaxant drug or positive pressure oxygen. Endotracheal intubation may be indicated in difficult cases. Diluents in Pentothal (thiopental sodium) ® Kits Ready-To-Mix Syringes and Vials (For preparing solutions of Thiopental Sodium for Injection, USP) Used as diluents for preparing solutions of Pentothal (Thiopental Sodium for Injection, USP) the small volumes of administered fluid (from Sterile Water for Injection in bottles and vials) and amounts of sodium chloride (from 0.9% Sodium Chloride Injection in Ready-to-Mix Syringes) are unlikely to pose a threat of fluid or sodium chloride overload. CONTRAINDICATIONS Absolute Contraindications Absence of suitable veins for intravenous administration, hypersensitivity (allergy) to barbiturates and variegate porphyria (South African) or acute intermittent porphyria. Relative Contraindications Severe cardiovascular disease, hypotension or shock, conditions in which the hypnotic effect may be prolonged or potentiated - excessive premedication, Addison's disease, hepatic or renal dysfunction, myxedema, increased blood urea, severe anemia, asthma, myasthenia gravis, and status asthmaticus. Diluents in Pentothal (thiopental sodium) ® Kits Ready-To-Mix Syringes and Vials (For preparing solutions of Thiopental Sodium for Injection, USP) Do not use unless the diluent is clear and the bottle or vial seal or syringe package is undamaged. Diluents in Pentothal (thiopental sodium) Kits, Ready-to-Mix Syringes or Vials should not be used for fluid or sodium chloride replacement.

SIDE EFFECTS Pentothal (thiopental sodium) Adverse reactions include respiratory depression, myocardial depression, cardiac arrhythmias, prolonged somnolence and recovery, sneezing, coughing, bronchospasm, laryngospasm and shivering. Anaphylactic and anaphylactoid reactions to Pentothal (thiopental sodium) (Thiopental Sodium for Injection, USP) have been reported. Symptoms, e.g., urticaria, bronchospasm, vasodilation and edema should be managed by conventional means. Rarely, immune hemolytic anemia with renal failure and radial nerve palsy have been reported. DRUG ABUSE AND DEPENDENCE WARNING: MAY BE HABIT FORMING. Thiopental sodium is classified as a Schedule III controlled substance. Diluents in Pentothal (thiopental sodium) ® Kits Ready-To-Mix Syringes and Vials (For preparing solutions of Thiopental Sodium for Injection, USP) Reactions which may occur because of the diluents, technique of preparation or mixing, or administration of reconstituted solutions of Pentothal (thiopental sodium) include febrile response or infection at the site of injection, venous thrombosis or phlebitis extending from the site of injection and extravasation. If an adverse reaction does occur, discontinue the injection, evaluate the patient, institute appropriate therapeutic countermeasures and save the remainder of unused solution (or the used container or syringe) for examination if deemed necessary. DRUG ABUSE AND DEPENDENCE None known. DRUG INTERACTIONS The following drug interactions have been reported with thiopental. Drug Effect Probenecid Prolonged action of thiopental Diazoxide Hypotension Zimelidine Thiopental antagonism Opioid analgesics Decreased antinociceptive action Aminophylline Thiopental antagonism Midazolam Synergism

WARNINGS Pentothal (thiopental sodium) KEEP RESUSCITATIVE AND ENDOTRACHEAL INTUBATION EQUIPMENT AND OXYGEN READILY AVAILABLE. MAINTAIN PATENCY OF THE AIRWAY AT ALL TIMES. This drug should be administered only by persons qualified in the use of intravenous anesthetics. Avoid extravasation or intra-arterial injection. WARNING: MAY BE HABIT FORMING. Diluents in Pentothal (thiopental sodium) ® Kits Ready-To-Mix Syringes and Vials (For preparing solutions of Thiopental Sodium for Injection, USP) Intravenous administration of Sterile Water for Injection, USP without a solute may result in hemolysis. Use aseptic technique for preparing Pentothal (thiopental sodium) solutions when using Pentothal (thiopental sodium) Kits, Syringes or Vials and during withdrawal from reconstituted single or multiple-use containers. Administer only clear reconstituted solutions. Use within 24 hours after reconstitution. Discard unused portions. PRECAUTIONS Pentothal (thiopental sodium) Observe aseptic precautions at all times in preparation and handling of Pentothal (Thiopental Sodium for Injection, USP) solutions. If used in conditions involving relative contraindications, reduce dosage and administer slowly. Care should be taken in administering the drug to patients with advanced cardiac disease, increased intracranial pressure, ophthalmoplegia plus, asthma, myasthenia gravis and endocrine insufficiency (pituitary, thyroid, adrenal, pancreas). Drug Interactions See DRUG INTERACTIONS section. Nursing Mothers Thiopental sodium readily crosses the placental barrier and small amounts may appear in the milk of nursing mothers following administration of large doses. Pregnancy Pregnancy Category C. Animal reproduction studies have not been conducted with Pentothal (thiopental sodium) . It is also not known whether Pentothal (thiopental sodium) can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Pentothal (thiopental sodium) should be given to a pregnant woman only if clearly needed. Diluents in Pentothal (thiopental sodium) ® Kits Ready-To-Mix Syringes and Vials (For preparing solutions of Thiopental Sodium for Injection, USP) Do not use unless solution is clear and container is undamaged. Inspect reconstituted (mixed) solutions of Pentothal (Thiopental Sodium for Injection, USP) for clarity and freedom from precipitation or discoloration prior to administration. Use reconstituted solution only if it is clear, free from precipitate and not discolored. Use Transfer Label in each Pentothal (thiopental sodium) Kit and affix to container of reconstituted solution to show concentration and time of preparation. Pregnancy Pregnancy Category C. Animal reproduction studies have not been conducted with sterile water for injection or sodium chloride injection. It is also not known whether sterile water or sodium chloride injection containing additives can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Sterile water for injection or sodium chloride injection with additives should be given to a pregnant woman only if clearly needed.