Pentothal Generic Name: thiopental sodium Brand Name: Pentothal side effects drug center pentothal (thiopental sodium) drug PROFESSIONAL SIDE EFFECTS Contents Drug Description Indications Dosage Side Effects & Drug Interactions Warnings Precautions Overdosage Contraindications Clinical Pharmacology Medication Guide Drug Description What is Pentothal and how is it used? Pentothal is a prescription medicine used as an anesthetic. Pentothal may be used alone or with other medications. Pentothal belongs to a class of drugs called Barbiturate. It is not known if Pentothal is safe and effective in children. What are the possible side effects of Pentothal? Pentothal may cause serious side effects including: severe pain, slowed breathing, dysfunction of the heart, irregular heartbeat, slowed heartbeat, numbness from the triceps down to the fingers, difficulty extending the wrist or fingers, difficulty pinching or grasping, muscle weakness in the arms, wrist drop, fatigue, dizziness, heart palpitations, pale skin, headache, confusion, yellowing of the skin or eyes (jaundice), enlargement of the spleen or liver, chills, fever, pain in the back and abdomen, and shock Get medical help right away, if you have any of the symptoms listed above. The most common side effects of Pentothal include: coughing, sneezing, hiccups, slowed breathing, slow heart rate, cardiac arrhythmias, prolonged sleepiness and recovery, and shivering Tell the doctor if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of Pentothal. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. 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. Indications INDICATIONS Pentothal Pentothal (Thiopental Sodium for Injection, USP) is indicated (1) as the sole anesthetic agent for brief (15 minute) procedures, (2) for induction of anesthesia prior to administration of other anesthetic agents, (3) to supplement regional anesthesia, (4) to provide hypnosis during balanced anesthesia with other agents for analgesia or muscle relaxation, (5) for the control of convulsive states during or following inhalation anesthesia, local anesthesia, or other causes, (6) in neurosurgical patients with increased intracranial pressure, if adequate ventilation is provided, and (7) for narcoanalysis and narcosynthesis in psychiatric disorders. Diluents in Pentothal (thiopental sodium) ® Kits Ready-To-Mix Syringes and Vials (For preparing solutions of Thiopental Sodium for Injection, USP) These products are indicated only for preparing Pentothal (Thiopental Sodium for Injection, USP) solutions for clinical use. Dosage DOSAGE AND ADMINISTRATION Pentothal (thiopental sodium) Pentothal (thiopental sodium) is administered by the intravenous route only. Individual response to the drug is so varied that there can be no fixed dosage. The drug should be titrated against patient requirements as governed by age, sex and body weight. Younger patients require relatively larger doses than middle-aged and elderly persons; the latter metabolize the drug more slowly. Pre-puberty requirements are the same for both sexes, but adult females require less than adult males. Dose is usually proportional to body weight and obese patients require a larger dose than relatively lean persons of the same weight. Premedication Premedication usually consists of atropine or scopolamine to suppress vagal reflexes and inhibit secretions. In addition, a barbiturate or an opiate is often given. Sodium pentobarbital injection (Nembutal®) is suggested because it provides a preliminary indication of how the patient will react to barbiturate anesthesia. Ideally, the peak effect of these medications should be reached shortly before the time of induction. Test Dose It is advisable to inject a small "test" dose of 25 to 75 mg (1 to 3 mL of a 2.5% solution) of Pentothal (Thiopental Sodium for Injection, USP) to assess tolerance or unusual sensitivity to Pentothal (thiopental sodium) , and pausing to observe patient reaction for at least 60 seconds. If unexpectedly deep anesthesia develops or if respiratory depression occurs, consider these possibilities: (1) the patient may be unusually sensitive to Pentothal (thiopental sodium) , (2) the solution may be more concentrated than had been assumed, or (3) the patient may have received too much premedication. Use in Anesthesia Moderately slow induction can usually be accomplished in the "average" adult by injection of 50 to 75 mg (2 to 3 mL of a 2.5% solution) at intervals of 20 to 40 seconds, depending on the reaction of the patient. Once anesthesia is established, additional injections of 25 to 50 mg can be given whenever the patient moves. Slow injection is recommended to minimize respiratory depression and the possibility of overdosage. The smallest dose consistent with attaining the surgical objective is the desired goal. Momentary apnea following each injection is typical, and progressive decrease in the amplitude of respiration appears with increasing dosage. Pulse remains normal or increases slightly and returns to normal. Blood pressure usually falls slightly but returns toward normal. Muscles usually relax about 30 seconds after unconsciousness is attained, but this may be masked if a skeletal muscle relaxant is used. The tone of jaw muscles is a fairly reliable index. The pupils may dilate but later contract; sensitivity to light is not usually lost until a level of anesthesia deep enough to permit surgery is attained. Nystagmus and divergent strabismus are characteristic during early stages, but at the level of surgical anesthesia, the eyes are central and fixed. Corneal and conjunctival reflexes disappear during surgical anesthesia. When Pentothal (Thiopental Sodium for Injection, USP) is used for induction in balanced anesthesia with a skeletal muscle relaxant and an inhalation agent, the total dose of Pentothal (thiopental sodium) can be estimated and then injected in two to four fractional doses. With this technique, brief periods of apnea may occur which may require assisted or controlled pulmonary ventilation. As an initial dose, 210 to 280 mg (3 to 4 mg/kg) of Pentothal (thiopental sodium) is usually required for rapid induction in the average adult (70 kg). When Pentothal (Thiopental Sodium for Injection, USP) is used as the sole anesthetic agent, the desired level of anesthesia can be maintained by injection of small repeated doses as needed or by using a continuous intravenous drip in a 0.2% or 0.4% concentration. (Sterile water should not be used as the diluent in these concentrations, since hemolysis will occur.) With continuous drip, the depth of anesthesia is controlled by adjusting the rate of infusion. Use in Convulsive States For the control of convulsive states following anesthesia (inhalation or local) or other causes, 75 to 125 mg (3 to 5 mL of a 2.5% solution) should be given as soon as possible after the convulsion begins. Convulsions following the use of a local anesthetic may require 125 to 250 mg of Pentothal (thiopental sodium) given over a ten minute period. If the convulsion is caused by a local anesthetic, the required dose of Pentothal (thiopental sodium) will depend upon the amount of local anesthetic given and its convulsant properties. Use in Neurosurgical Patients with Increased Intracranial Pressure In neurosurgical patients, intermittent bolus injections of 1.5 to 3.5 mg/kg of body weight may be given to reduce intraoperative elevations of intracranial pressure, if adequate ventilation is provided. Use in Psychiatric Disorders For narcoanalysis and narcosynthesis in psychiatric disorders, premedication with an anticholinergic agent may precede administration of Pentothal. After a test dose, Pentothal (Thiopental Sodium for Injection, USP) is injected at a slow rate of 100 mg/mm (4 mL/min of a 2.5% solution) with the patient counting backwards from 100. Shortly after counting becomes confused but before actual sleep is produced, the injection is discontinued. Allow the patient to return to a semidrowsy state where conversation is coherent. Alternatively, Pentothal (thiopental sodium) may be administered by rapid I.V. drip using a 0.2% concentration in 5% dextrose and water. At this concentration, the rate of administration should not exceed 50 mL/min. MANAGEMENT OF SOME COMPLICATIONS Respiratory depression (hypoventilation, apnea), which may result from either unusual responsiveness to Pentothal (thiopental sodium) or overdosage, is managed as stated above. Pentothal (thiopental sodium) should be considered to have the same potential for producing respiratory depression as an inhalation agent, and patency of the airway must be protected at all times. Laryngospasm may occur with light Pentothal (thiopental sodium) narcosis at intubation, or in the absence of intubation if foreign matter or secretions in the respiratory tract create irritation. Laryngeal and bronchial vagal reflexes can be suppressed, and secretions minimized by giving atropine or scopolamine premedication and a barbiturate or opiate. Use of a skeletal muscle relaxant or positive pressure oxygen will usually relieve laryngospasm. Tracheostomy may be indicated in difficult cases. Myocardial depression, proportional to the amount of drug in direct contact with the heart, can occur and may cause hypotension, particularly in patients with an unhealthy myocardium. Arrhythmias may appear if PCO2 is elevated, but they are uncommon with adequate ventilation. Management of myocardial depression is the same as for overdosage. Pentothal (Thiopental Sodium for Injection, USP) does not sensitize the heart to epinephrine or other sympathomimetic amines. Extra vascular infiltration should be avoided. Care should be taken to insure that the needle is within the lumen of the vein before injection of Pentothal (thiopental sodium) . Extravascular injection may cause chemical irritation of the tissues varying from slight tenderness to venospasm, extensive necrosis and sloughing. This is due primarily to the high alkaline pH (10 to 11) of clinical concentrations of the drug. If extravasation occurs, the local irritant effects can be reduced by injection of 1% procaine locally to relieve pain and enhance vasodilatation. Local application of heat also may help to increase local circulation and removal of the infiltrate. Intra-arterial injection can occur inadvertently, especially if an aberrant superficial artery is present at the medial aspect of the antecubital fossa. The area selected for intravenous injection of the drug should be palpated for detection of an underlying pulsating vessel. Accidental intra-arterial injection can cause arteriospasm and severe pain along the course of the artery with blanching of the arm and fingers. Appropriate corrective measures should be instituted promptly to avoid possible development of gangrene. Any patient complaint of pain warrants stopping the injection. Methods suggested for dealing with this complication vary with the severity of symptoms. The following have been suggested: 1. Dilute the injected Pentothal (Thiopental Sodium for Injection, USP) by removing the tourniquet and any restrictive garments. 2. Leave the needle in place, if possible. 3. Inject the artery with a dilute solution of papaverine, 40 to 80 mg, or 10 mL of 1% procaine, to inhibit smooth muscle spasm. 4. If necessary, perform sympathetic block of the brachial plexus and/or stellate ganglion to relieve pain and assist in opening collateral circulation. Papaverine can be injected into the subclavian artery, if desired. 5. Unless otherwise contraindicated, institute immediate heparinization to prevent thrombus formation. 6. Consider local infiltration of an alpha-adrenergic blocking agent such as phentolamine into the vasospastic area. 7. Provide additional symptomatic treatment as required. Shivering after Pentothal (thiopental sodium) anesthesia, manifested by twitching face muscles and occasional progression to tremors of the arms, head, shoulder and body, is a thermal reaction due to increased sensitivity to cold. Shivering appears if the room environment is cold and if a large ventilatory heat loss has been sustained with balanced inhalation anesthesia employing nitrous oxide. Treatment consists of warming the patient with blankets, maintaining room temperature near 22°C (72°F), and administration of chlorpromazine or methylphenidate. PREPARATION OF SOLUTIONS Pentothal Pentothal (Thiopental Sodium for Injection, USP) is supplied as a yellowish, hygroscopic powder in a variety of different containers. Solutions should be prepared aseptically with one of the three following diluents: Sterile Water for Injection, USP, 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP. Clinical concentrations used for intermittent intravenous administration vary between 2.0% and 5.0%. A 2.0% or 2.5% solution is most commonly used. A 3.4% concentration in sterile water for injection is isotonic; concentrations less than 2.0% in this diluent are not used because they cause hemolysis. For continuous intravenous drip administration, concentrations of 0.2% or 0.4% are used. Solutions may be prepared by adding Pentothal (thiopental sodium) to 5% Dextrose Injection, USP, 0.9% Sodium Chloride Injection, USP or Normosol®-R pH 7.4. Since Pentothal (thiopental sodium) contains no added bacteriostatic agent, extreme care in preparation and handling should be exercised at all times to prevent the introduction of microbial contaminants. Solutions should be freshly prepared and used promptly; when reconstituted for administration to several patients, unused portions should be discarded after 24 hours. Sterilization by heating should not be attempted. WARNING: The 2.5 g and larger sizes contain adequate medication for several patients. COMPATIBILITY Pentothal Any solution of Pentothal (Thiopental Sodium for Injection, USP) with a visible precipitate should not be administered. The stability of Pentothal (thiopental sodium) solutions depends upon several factors, including the diluent, temperature of storage and the amount of carbon dioxide from room air that gains access to the solution. Any factor or condition which tends to lower pH (increase acidity) of Pentothal (thiopental sodium) solutions will increase the likelihood of precipitation of thiopental acid. Such factors include the use of diluents which are too acidic and the absorption of carbon dioxide which can combine with water to form carbonic acid. Solutions of succinylcholine, tubocurarine or other drugs which have an acid pH should not be mixed with Pentothal (thiopental sodium) solutions. The most stable solutions are those reconstituted in water or isotonic saline, kept under refrigeration and tightly stoppered. The presence or absence of a visible precipitate offers a practical guide to the physical compatibility of prepared solutions of Pentothal (thiopental sodium) . CALCULATIONS FOR VARIOUS CONCENTRATIONS Concentration mounts to Use Desired Pentothal Diluent Percent mg/ml g ml 0.2 2 1 500 0.4 4 1 250 2 500 2.0 20 5 250 10 500 2.5 25 1 40 5 200 5 50 1 20 5 100 Reconstituted solutions of Pentothal (Thiopental Sodium for Injection, USP) should be inspected visually for particulate matter and discoloration, whenever solution and container permit. Diluents in Pentothal (thiopental sodium) ® Kits Ready-To-Mix Syringes and Vials (For preparing solutions of Thiopental Sodium for Injection, USP) Pentothal (thiopental sodium) solutions should be administered only by intravenous injection and by individuals experienced in the conduct of intravenous anesthesia. The volume and choice of diluent for preparing Pentothal (Thiopental Sodium for Injection, USP) solutions for clinical use depends on the concentration and vehicle desired. Pentothal (thiopental sodium) Kits provide only Sterile Water for Injection as the diluent for individual or multi-patient use; Pentothal (thiopental sodium) Ready-to-Mix Syringes provide only 0.9% Sodium Chloride Injection, USP as the diluent for individual patient use; vials provide only Sterile Water for Injection, USP as the diluent for individual patient use. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. See PRECAUTIONS. HOW SUPPLIED Pentothal (thiopental sodium) Pentothal (thiopental sodium) is available in a variety of sizes and containers shown at the end of this section (See TABLE for list of sizes available). Diluents in Pentothal (thiopental sodium) ® Kits Ready-To-Mix Syringes and Vials (For preparing solutions of Thiopental Sodium for Injection, USP) The diluent in Pentothal (thiopental sodium) Kits is supplied in various size containers with various dosage sizes of Pentothal (Thiopental Sodium for Injection, USP). Kits include all items needed for aseptic transfer of Pentothal (thiopental sodium) powder from a squeeze bottle into the diluent container. The diluent in Pentothal (thiopental sodium) Ready-to-Mix Syringes is supplied in a separate container to permit mixing with the Pentothal (thiopental sodium) in a powder vial to permit immediate intravenous injection of reconstituted solution into a vein or attachment to a standard stopcock assembly. Vials are supplied in cartons with different dosage sizes of Pentothal (thiopental sodium) for preparing 2.0% or 2.5% concentrations by using a separate syringe (not supplied) for mixing. See table for list of sizes available. TABLE: Pentothal® (Thiopental Sodium for Injection, USP) and Diluent in Kits, Ready-to-Mix Syringes and Ready-to-Mix LifeShield® Syringes List No. Pentothal Pentothal Container Diluent (mL)* Diluent Container Theoretical Reconstituted Conc. 6259 (Kit) 25 g Squeeze Bottle W (125) PF Bottle 2% (20 mg/mL) 6108 (Kit) 5 g Squeeze Bottle W (250) PF Bottle 2% (20 mg/mL) 6244 (Kit) 1 g Squeeze Bottle W (40) PF Bottle 2.5% (25 mg/mL) 6260 (Kit) 2.5 g Squeeze Bottle W (100) PF 2.5% (25 mg/mL) 6504 (Kit) 5 g Squeeze Bottle W (200) Bottle 2.5% (25 mg/mL) 6435 (Kit) 1 g Vial W (50) Plastic Vial 2% (20 mg/mL) 3329 (Kit) 500 mg Vial W (20) Plastic Vial 2.5% (25 mg/mL) 9097 (Kit) 1 g Vial W (50) Plastic Vial 2% (20 mg/mL) 9088 (Kit) 500 mg Vial W (20) Plastic Vial 2.5% (25 mg/mL) 6246 (Ready-to-Mix Syringe) 400 mg Syringe 5 (20) Syringe 2% (20 mg/mL) 6241 (Ready-to-Mix Syringe) 250 mg Syringe 5 (10) Syringe 2.5% (25 mg/mL) 6243 (Ready-to-Mix Syringe) 500 mg Syringe S (20) Syringe 2.5% (25 mg/mL) 3351 (Ready-to-Mix LifeShield Syringe) 250 mg Syringe S (10) Syringe 2.5% (25 mg/mL) 3352 (Ready-to-Mix LifeShield Syringe) 400 mg Syringe 5 (20) Plastic Vial 2% (20 mg/mL) 3353 (Ready-to-Mix LifeShield Syringe) 500 mg Syringe S (20) Plastic Vial 2.5% (25 mg/mL) 6418 (Ready-to-Mix Syringe) 250 mg Syringe W (10) Plastic Vial 2.5% (25 mg/mL) 6419 (Ready-to-Mix Syringe) 400 mg Syringe W (20) Plastic Vial 2% (20 mg/mL) 6420 (Ready-to-Mix Syringe) 500 mg Syringe W (20) Plastic Vial 2.5% (25 mg/mL) PF - denotes Partial-Fill W - denotes Sterile Water for Injection, USP S - denotes 0.9% Sodium Chloride Injection, USP * Diluent containers are slightly overfilled to assure compliance with USP minimum fill volume requirements. Storage: Store at controlled room temperature 15° to 30°C( 59° to 86°F). Keep reconstituted solution in a cool place. Caution: Federal (USA) law prohibits dispensing without prescription. Side Effects & Drug Interactions 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 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 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. Overdosage 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 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. Clinical Pharmacology 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. Medication Guide PATIENT INFORMATION See WARNINGS, PRECAUTIONS and CONTRAINDICATIONS.
