Apo-Ibuprofen FC

Apo-Ibuprofen FC may be available in the countries listed below.

Ingredient matches for Apo-Ibuprofen FC

Ibuprofen

Ibuprofen is reported as an ingredient of Apo-Ibuprofen FC in the following countries:

• Vietnam

International Drug Name Search

Fenobarbital Cipa

Fenobarbital Cipa may be available in the countries listed below.

Ingredient matches for Fenobarbital Cipa

Phenobarbital

Phenobarbital is reported as an ingredient of Fenobarbital Cipa in the following countries:

• Peru

International Drug Name Search

Risperidon Alternova

Risperidon Alternova may be available in the countries listed below.

Ingredient matches for Risperidon Alternova

Risperidone

Risperidone is reported as an ingredient of Risperidon Alternova in the following countries:

• Austria

International Drug Name Search

Morefine

Morefine may be available in the countries listed below.

Ingredient matches for Morefine

Chlorpromazine

Chlorpromazine hydrochloride (a derivative of Chlorpromazine) is reported as an ingredient of Morefine in the following countries:

• Taiwan

International Drug Name Search

Noradrénaline Renaudin sans conservateur

Noradrénaline Renaudin sans conservateur may be available in the countries listed below.

Ingredient matches for Noradrénaline Renaudin sans conservateur

Norepinephrine

Norepinephrine tartrate (a derivative of Norepinephrine) is reported as an ingredient of Noradrénaline Renaudin sans conservateur in the following countries:

• France

International Drug Name Search

Rifazid

Rifazid may be available in the countries listed below.

Ingredient matches for Rifazid

Isoniazid

Isoniazid is reported as an ingredient of Rifazid in the following countries:

• Hungary

Rifampicin

Rifampicin is reported as an ingredient of Rifazid in the following countries:

• Hungary

International Drug Name Search

Normaton

Normaton may be available in the countries listed below.

Ingredient matches for Normaton

Buspirone

Buspirone hydrochloride (a derivative of Buspirone) is reported as an ingredient of Normaton in the following countries:

• Colombia


• Dominican Republic


• El Salvador


• Guatemala


• Honduras


• Panama

International Drug Name Search

Calcium Trisodium Pentetate

Scheme

Rec.INN

CAS registry number (Chemical Abstracts Service)

0012111-24-9

Chemical Formula

C14-H18-Ca-N3-Na3-O10

Molecular Weight

497

Therapeutic Category

Antidote: Chelating agent

Chemical Name

Calciate(3-), [N,N-bis[2-[bis(carboxymethyl)amino]ethyl]glycinato(5-)]-, trisodium

Foreign Names

• Calcii Trinatrii Pentetas (Latin)
• Calcium-trinatrium pentetat (German)
• Pentétate de calcium trisodique (French)
• Pentetato calcico trisodico (Spanish)

Generic Names

• Calcium Trisodium Pentetate (OS: BAN)
• Pentetate Calcium Trisodium (OS: USAN)
• Pentétate de calcium trisodique (OS: DCF)
• Ca-Chel-330 (IS)
• NSC 34249 (IS)

Brand Names

• Amerscan Pentetate II
  Amersham, France



• Calcium Edetate de Sodium
  IFET, Greece



• Ditripentat-Heyl
  Heyl, Germany



• Pentetate Calcium Trisodium
  Hameln, United States

International Drug Name Search

Glossary

BAN	British Approved Name
DCF	Dénomination Commune Française
IS	Inofficial Synonym
OS	Official Synonym
Rec.INN	Recommended International Nonproprietary Name (World Health Organization)
USAN	United States Adopted Name

Click for further information on drug naming conventions and International Nonproprietary Names.

Laitun

Laitun may be available in the countries listed below.

Ingredient matches for Laitun

Ciprofloxacin

Ciprofloxacin hydrochloride (a derivative of Ciprofloxacin) is reported as an ingredient of Laitun in the following countries:

• Philippines

International Drug Name Search

Rifamicina SV Denver

Rifamicina SV Denver may be available in the countries listed below.

Ingredient matches for Rifamicina SV Denver

Rifamycin

Rifamycin sodium salt (a derivative of Rifamycin) is reported as an ingredient of Rifamicina SV Denver in the following countries:

• Argentina

International Drug Name Search

Glibenclamida Vannier

Glibenclamida Vannier may be available in the countries listed below.

Ingredient matches for Glibenclamida Vannier

Glibenclamide

Glibenclamide is reported as an ingredient of Glibenclamida Vannier in the following countries:

• Argentina

International Drug Name Search

Varicide

Varicide may be available in the countries listed below.

In some countries, this medicine may only be approved for veterinary use.

Ingredient matches for Varicide

Benzalkonium Chloride

Benzalkonium chloride (a derivative of Benzalkonium) is reported as an ingredient of Varicide in the following countries:

• New Zealand

International Drug Name Search

Confatanin

Confatanin may be available in the countries listed below.

Ingredient matches for Confatanin

Loxoprofen

Loxoprofen sodium salt (a derivative of Loxoprofen) is reported as an ingredient of Confatanin in the following countries:

• Japan

International Drug Name Search

Betapyr

Betapyr may be available in the countries listed below.

Ingredient matches for Betapyr

Pyridoxine

Pyridoxine hydrochloride (a derivative of Pyridoxine) is reported as an ingredient of Betapyr in the following countries:

• Belgium


• Luxembourg

Thiamine

Thiamine hydrochloride (a derivative of Thiamine) is reported as an ingredient of Betapyr in the following countries:

• Belgium


• Luxembourg

International Drug Name Search

Bupivacaine Hydrochloride

Class: Local Anesthetics
CAS Number: 14252-80-3
Brands: Marcaine, Marcaine Spinal, Marcaine Hydrochloride with Epinephrine, Sensorcaine, Sensorcaine-MPF, Sensorcaine-MPF Spinal, Sensorcaine with Epinephrine, Sensorcaine-MPF with Epinephrine

• 
  

  Use of the 0.75% solution of bupivacaine hydrochloride not recommended for obstetrical epidural anesthesia.^{211 212} Cardiac arrest with difficult resuscitation or death reported in patients receiving bupivacaine hydrochloride (generally the 0.75% concentration) for obstetrical epidural anesthesia.^{211 212}

  
  


• 
  

  Reserve 0.75% solution for surgical procedures that require a high degree of muscle relaxation and prolonged anesthetic effect.²¹¹

  
  

Introduction

Long-acting local anesthetic (amide type).^{211 212 a}

Uses for Bupivacaine Hydrochloride

Local or Regional Anesthesia

Local or regional anesthesia or analgesia in surgical procedures (including oral surgery), diagnostic and therapeutic procedures, and obstetrical procedures.^{211 212}

Bupivacaine Hydrochloride Dosage and Administration

General

• 
  

  Determine dosage based on type and extent of surgical procedure, area to be anesthetized, vascularity of tissues, number of neuronal segments to be blocked, depth and duration of anesthesia, degree of muscular relaxation, individual tolerance, and physical condition of the patient.^{211 212} Use smallest dose required to produce the desired effect.^{211 212}

  
  


• 
  

  During major regional nerve blocks, administer IV fluids via an indwelling catheter to ensure a functioning IV pathway.^{211 212}

  
  

Administration

Injection

For solution and drug compatibility information, see Compatibility under Stability.

Administer by local infiltration, peripheral nerve block, retrobulbar block, sympathetic block, lumbar epidural block, caudal block, or subarachnoid (spinal) block.^{211 212} IV regional anesthesia (Bier block) not recommended due to risk of cardiac arrest and death.²¹¹ Has been administered by continuous intra-articular infusion† (e.g., for control of postoperative pain); however, such use associated with chondrolysis.^{200 201 202 203 204 205 206 207 208 209 211 212 213 214} (See Risk of Chondrolysis Associated with Intra-articular Infusions of Local Anesthetics under Cautions.)

Consult specialized references for specific techniques and procedures for administering local anesthetics.^{211 212}

Avoid rapid injection of large volumes; when feasible, administer in fractional (incremental) doses.²¹¹ Aspirate prior to injections to avoid intravascular administration and to either confirm entry into the subarachnoid space (for spinal anesthesia) or avoid inadvertent subarachnoid injection.^{211 212 215}

For caudal or epidural block, use single-dose ampuls or vials only.²¹¹ Do not use multiple-dose vials containing antimicrobial preservatives (e.g., methylparaben), since safety of intrathecal administration using these preparations not established.²¹¹

For chemical disinfection of container surface, moisten cotton or gauze with isopropyl (rubbing) alcohol (91%) or ethyl alcohol (70%) and wipe ampul or vial stopper thoroughly just prior to use.²¹¹

Dosage

Available as bupivacaine hydrochloride, as fixed combination containing bupivacaine hydrochloride and epinephrine bitartrate, and as bupivacaine hydrochloride in dextrose injection.^{211 212} Dosage expressed in terms of bupivacaine hydrochloride.²¹²

Pediatric Patients

Local or Regional Anesthesia

Local Infiltration, Peripheral/Sympathetic Nerve Block, Lumbar Epidural/Caudal Block

Children ≥12 years of age: Use lower dosages than those suggested for healthy adults (see Adults under Dosage and Administration).²¹¹

Adults

Local or Regional Anesthesia

Local Infiltration

Administer bupivacaine hydrochloride 0.25% solution (with or without epinephrine) at dosages up to maximum dosage (see Prescribing Limits under Dosage and Administration).²¹¹

Lumbar Epidural Block

Prior to lumbar epidural anesthesia, administer test dose to detect accidental intravascular injection.²¹¹ Test dose should contain 10–15 mcg epinephrine (when clinical conditions permit) and 10–15 mg (2–3 mL) of 0.5% bupivacaine hydrochloride (or equivalent dose of a short-acting amide type local anesthetic such as 30–40 mg of lidocaine hydrochloride).²¹¹ Following injection of test dose, monitor for increase in heart rate.²¹¹

0.75% solution is for single-dose use; not for intermittent epidural technique.²¹¹ Reserve for surgical procedures requiring a high degree of muscle relaxation and prolonged anesthetic effect.²¹¹

0.75% solution is not for obstetrical anesthesia; in obstetrics, use 0.25 or 0.5% solutions only.²¹¹ (See Boxed Warning and see Risks Associated with Obstetrical Use of Bupivacaine Hydrochloride 0.75% Injection under Cautions.)

75–150 mg (10–20 mL) of bupivacaine hydrochloride 0.75% solution (with or without epinephrine) produces complete motor blockade.²¹¹ Administer in incremental doses of 3–5 mL.²¹¹ Allow sufficient time between doses to detect toxic manifestations of unintentional intravascular or intrathecal injection.²¹¹

50–100 mg (10–20 mL) of bupivacaine hydrochloride 0.5% solution (with or without epinephrine) produces moderate to complete motor blockade.²¹¹ Administer in incremental doses of 3–5 mL.²¹¹ Allow sufficient time between doses to detect toxic manifestations of unintentional intravascular or intrathecal injection.²¹¹

25–50 mg (10–20 mL) of bupivacaine hydrochloride 0.25% solution (with or without epeniphrine) produces partial motor blockade.²¹¹

Caudal Block

75–150 mg (15–30 mL) of bupivacaine hydrochloride 0.5% solution (with or without epinephrine) produces moderate to complete motor blockade.²¹¹

37.5–75 mg (15–30 mL) of bupivacaine hydrochloride 0.25% solution (with or without epinephrine) produces moderate motor blockade.²¹¹

Peripheral Nerve Block

25 mg (5 mL) to maximum dosage (see Prescribing Limits under Dosage and Administration) of bupivacaine hydrochloride 0.25% solution (with or without epinephrine) produces moderate to complete motor blockade.²¹¹

12.5 mg (5 mL) to maximum dosage (see Prescribing Limits under Dosage and Administration) of bupivacaine hydrochloride 0.5% solution (with or without epinephrine) produces moderate to complete motor blockade.²¹¹

Retrobulbar Block

15–30 mg (2–4 mL) of bupivacaine hydrochloride 0.75% solution (with or without epinephrine) produces complete motor blockade.²¹¹

Sympathetic Block

50–125 mg (20–50 mL) of bupivacaine hydrochloride 0.25% solution.²¹¹

Anesthesia in Maxillary and Mandibular Area (for oral surgery)

9 mg (1.8 mL) up to 90 mg (18 mL) of bupivacaine hydrochloride 0.5% solution per dental sitting.^{215 a}

Subarachnoid (Spinal) Block for Vaginal Delivery

6 mg (0.8 mL) of bupivacaine hydrochloride 0.75% in dextrose 8.25% injection produces complete motor and sensory block.²¹²

Subarachnoid (Spinal) Block for Cesarean Section

7.5–10.5 mg (1–1.4 mL) of bupivacaine hydrochloride 0.75% in dextrose 8.25% injection produces complete motor and sensory block.²¹²

Subarachnoid (Spinal) Block for Lower Extremity and Perineal Procedures (e.g., TURP, vaginal hysterectomy)

7.5 mg (1 mL) of bupivacaine hydrochloride 0.75% in dextrose 8.25% injection produces complete motor and sensory block.²¹²

Subarachnoid (Spinal) Block for Lower Abdominal Procedures (e.g., abdominal hysterectomy, tubal ligation, appendectomy)

12 mg (1.6 mL) of bupivacaine hydrochloride 0.75% in dextrose 8.25% injection produces complete motor and sensory block.²¹²

Prescribing Limits

Adults

Local or Regional Anesthesia

Local Infiltration, Peripheral/Sympathetic Nerve Block, Lumbar Epidirual/Caudal Block

Most experience to date has involved single doses up to 175 mg (without epinephrine) or 225 mg (with epinephrine 1:200,000).²¹¹

Maximum 400 mg in any 24-hour period.²¹¹

Special Populations

Hepatic Impairment

Reduce dosage in patients with hepatic impairment.^{211 212}

Geriatric Patients

Reduce dosage in geriatric patients.^{211 212 215}

Other Populations

Reduce dosage in patients with cardiac disease, debilitated patients, and acutely ill patients.^{211 212 215} Also reduce dosage in patients with increased intra-abdominal pressure (including obstetrical patients) undergoing spinal anesthesia.²¹²

Cautions for Bupivacaine Hydrochloride

Contraindications

• 
  

  Bupivacaine hydrochloride used for obstetrical paracervical block (this technique has resulted in fetal bradycardia and death).²¹¹

  
  


• 
  

  Contraindications to spinal anesthesia: severe hemorrhage, severe hypotension or shock, arrhythmias (e.g., complete heart block) that severely restrict cardiac output, local infection at site of lumbar puncture, and septicemia.²¹²

  
  


• 
  

  Known hypersensitivity to bupivacaine, other local anesthetics of the amide type, sodium metabisulfite, or any ingredients in the formulation.

  
  

Warnings/Precautions

Warnings

Risks Associated with Obstetrical Use of Bupivacaine Hydrochloride 0.75% Injection

Risk of seizures, cardiac arrest, difficult resuscitation, or death following obstetrical epidural block (possibly due to systemic toxicity secondary to unintentional intravascular injection).²¹¹

Not recommended for obstetrical anesthesia.²¹¹ Reserve for surgical procedures requiring a high degree of muscle relaxation and prolonged anesthetic effect.²¹¹

Experience of Supervising Clinician

Should be used only by clinicians who are sufficiently knowledgeable in the diagnosis and management of dose-related toxicity and other acute emergencies that might arise.^{211 212 215} Oxygen, resuscitative equipment, drugs, and personnel required for treatment of adverse reactions must be immediately available.^{211 212 215} Delay in proper management of dose-related toxicity may result in acidosis, cardiac arrest, and, possibly, death.^{211 212 215}

Risk of Chondrolysis Associated with Intra-articular Infusions of Local Anesthetics

Chondrolysis (necrosis and destruction of articular cartilage) reported in patients receiving continuous intra-articular infusions of local anesthetics, administered for 48–72 hours via elastomeric infusion devices, for treatment of postoperative pain.^{200 201 202 203 204 205 206 207 208 209 211 212 213 214} Primarily observed in the shoulder joint following arthroscopic or other shoulder surgery.^{200 211 212 213 214} May result in long-term disability; often requires intervention (e.g., debridement, arthroplasty).^{200 202 203 204 205 206 209 211 212 213 214} Not known whether the drug, infusion device, and/or other factors contributed to the development of chondrolysis.^{200 201} Neither local anesthetics nor elastomeric infusion devices are approved for use for continuous intra-articular infusion therapy.^{200 201 211 212 213 214}

Accidental Intravascular Injection

Accidental intravascular injection may result in confusion, seizures, CNS excitement and/or depression, myocardial depression, coma, and/or respiratory arrest.^{211 212} (See CNS Effects and also see Cardiovascular Effects, under Cautions.)

Aspirate prior to administration to guard against intravascular injection.^{211 212}

Injection During Uterine Contractions

Do not inject spinal anesthetics during uterine contractions, since spinal fluid current may carry drug further cephalad than desired.²¹²

Epinephrine Administration

Some bupivacaine hydrochloride preparations contain epinephrine, which may cause ischemic injury or necrosis.^{211 212} Consider usual precautions associated with epinephrine administration.^{211 212} (See Cardiovascular Effects under Cautions.)

Sensitivity Reactions

Hypersensitivity Reactions and Cross Hypersensitivity

Allergic reactions are rare.

Possible urticaria, pruritus, erythema, angioneurotic edema (including laryngeal edema), tachycardia, sneezing, nausea, vomiting, dizziness, syncope, excessive sweating, elevated temperature, and anaphylactoid reactions (including severe hypotension).^{211 212}

Cross hypersensitivity between amide-type local anesthetics reported.^{211 212}

Sulfite Sensitivity

Some epinephrine-containing bupivacaine preparations contain sodium metabisulfite, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.²¹¹

General Precautions

CNS Effects

Toxic plasma concentrations of local anesthetics (resulting from systemic absorption) associated with adverse CNS effects (e.g., restlessness, anxiety, dizziness, tinnitus, blurred vision, tremors, drowsiness, seizures).^{211 212}

Carefully monitor level of consciousness after each local anesthetic injection.^{211 212}

Cardiovascular Effects

Toxic plasma concentrations of local anesthetics (resulting from systemic absorption) associated with adverse cardiovascular effects (e.g., decreased cardiac output, heart block, hypotension, bradycardia, ventricular arrhythmias, cardiac arrest).^{211 212} Carefully monitor cardiovascular and respiratory vital signs after each local anesthetic injection.^{211 212}

Use with caution in patients with impaired cardiovascular function, hypotension, or heart block.^{211 212}

Possible peripheral vasodilation and hypotension following spinal anesthesia; monitor BP carefully, particularly in early phases of anesthesia.²¹² Use spinal anesthesia with caution in patients with severe disturbances of cardiac rhythm, shock, or heart block.²¹²

Some bupivacaine hydrochloride preparations contain epinephrine; risk of exaggerated vasoconstrictor response in patients with hypertensive vascular disease.²¹¹ Use with caution and in carefully restricted quantities in areas of the body supplied by end arteries or having otherwise compromised blood supply (e.g., digits, nose, external ear, penis).²¹¹

Familial Malignant Hyperthermia

Many drugs used during the conduct of anesthesia may trigger familial malignant hyperthermia; not known whether amide-type local anesthetics trigger this reaction.^{211 212} However, standard protocol for management should be available.^{211 212} Early unexplained signs of tachycardia, tachypnea, labile BP, and metabolic acidosis may precede temperature elevation.^{211 212} If familial malignant hyperthermia is confirmed, discontinue triggering agent and initiate appropriate therapy (e.g., oxygen, dantrolene) and other supportive measures.^{211 212}

Preexisting Conditions Precluding Use of Spinal Anesthesia

Conditions that may preclude the use of spinal anesthesia (depending upon the clinician’s evaluation of the situation and ability to manage potential complications) include preexisting CNS disease (e.g., disease associated with pernicious anemia, poliomyelitis, syphilis, tumor); hematological disorders predisposing to coagulopathies; current anticoagulant therapy; chronic backache; preoperative headache; hypotension or hypertension; technical problems (persistent paresthesias, persistent bloody tap); arthritis or spinal deformity; extremes of age; and psychosis or other causes of poor patient cooperation.²¹²

Use of Fixed Combination

When used in fixed combination with other agents, consider the cautions, precautions, and contraindications associated with the concomitant agents.

Specific Populations

Pregnancy

Category C.^{211 212}

Labor and Delivery

Maternal hypotension reported.^{211 212} To prevent decreases in BP, elevate patient’s legs and position patient on her left side.^{211 212} Monitor fetal heart rate continuously; electronic fetal monitoring highly advisable.^{211 212}

Epidural anesthesia may prolong second stage of labor (by removing parturient’s reflex urge to bear down or by interfering with motor function); may increase need for forceps assistance.^{211 212}

Possible diminished muscle strength and tone on neonate’s first or second day of life.^{211 212}

Lactation

Distributed into milk.²¹¹ Discontinue nursing or the drug.²¹¹

Pediatric Use

Bupivacaine hydrochloride injection with or without epinephrine not recommended in children <12 years of age.²¹¹ IV infusion associated with high plasma concentrations and seizures; high plasma concentrations associated with adverse cardiovascular effects.²¹¹

Bupivacaine hydrochloride in dextrose injection not recommended in children <18 years of age.²¹²

Geriatric Use

Increased risk of hypotension, particularly in patients with hypertension.²¹¹ Dosage adjustments recommended.^{211 212}

Possible increased risk of toxicity in geriatric patients with renal impairment; monitor renal function.²¹¹

Hepatic Impairment

Possible increased risk of toxicity, particularly in patients with severe hepatic impairment.^{211 212} Use with caution.^{211 212} Dosage adjustments recommended.^{211 212}

Renal Impairment

Possible increased risk of toxicity.²¹¹

Common Adverse Effects

Adverse CNS and cardiovascular effects, respiratory paralysis, underventilation.^{211 212} (See CNS Effects and also see Cardiovascular Effects, under Cautions.)

Interactions for Bupivacaine Hydrochloride

Consider usual drug interactions associated with epinephrine administration.^{211 212}

Specific Drugs

Drug	Interaction	Comments
Anesthetics, general	Possible serious cardiac arrhythmias due to epinephrine component211 212
Antidepressants, tricyclics	Possible severe, prolonged hypertension due to epinephrine component211 212	Avoid concomitant use;211 212 if must be used concomitantly, careful monitoring is required211 212
Butyrophenones	Possible reduction or reversal of pressor effect of epinephrine211 212
Ergot alkaloid oxytocics (ergonovine, methylergonovine)	Possible severe, persistent hypertension or cerebrovascular accidents due to epinephrine component211 212	Avoid concomitant use212
MAO inhibitors	Possible severe, prolonged hypertension due to epinephrine component211 212	Avoid concomitant use;211 212 if must be used concomitantly, careful monitoring is required211 212
Phenothiazines	Possible reduction or reversal of pressor effect of epinephrine211 212	Avoid concomitant use;211 212 if must be used concomitantly, careful monitoring is required211 212

Bupivacaine Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Systemic absorption dependent upon total dose and concentration administered, route of administration, vascularity of administration site, and presence or absence of epinephrine in formulation.^{211 212}

Peak blood concentrations achieved approximately 30–45 minutes following injection for caudal, epidural, or peripheral nerve block.²¹¹

Onset

Onset within 2–10 minutes following local infiltration or nerve block (for dental anesthesia) with 0.5% solution.^{215 a}

Onset within 4–17 minutes following epidural, caudal, peripheral, or sympathetic block with 0.25 or 0.5% solution.^a More rapid onset following epidural block with 0.75% solution.^a

Following 12-mg injection for spinal block, sensory blockade occurs within 1 minute; motor blockade occurs within 15 minutes.²¹²

Duration

Longer duration of anesthesia compared with other commonly used local anesthetics.^{211 212}

Duration of up to 7 minutes following local infiltration or nerve block (for dental anesthesia) with 0.5% solution.^{215 a}

Duration of 3–7 minutes following epidural, caudal, peripheral, or sympathetic block with 0.25 or 0.5% solution.^a Slightly longer duration (6–9 hours) with 0.75% solution.^a

Following a 12-mg injection for spinal block, sensory blockade persists for 2 hours (with or without 0.2 mg epinephrine); motor blockade persists for 3.5 hours (without epinephrine) or 4.5 hours (with 0.2 mg epinephrine).²¹² Similar duration of sensory blockade but shorter duration of motor blockade compared with mg-equivalent dose of tetracaine.²¹²

Special Populations

Increased peak plasma concentrations in geriatric patients.²¹¹ Maximal spread of analgesia and maximal motor blockade achieved more rapidly than in younger patients.²¹¹

Distribution

Extent

Local anesthetics are distributed to some extent to all body tissues, with high concentrations found in highly perfused organs (e.g., liver, lungs, heart, brain).^{211 212}

Lower degree of placental transmission than other parenteral local anesthetics.^a Distributed into milk.²¹¹

Plasma Protein Binding

95%.^{211 212}

Elimination

Metabolism

Systemically absorbed bupivacaine is metabolized in the liver via conjugation with glucuronic acid.^{211 212}

Elimination Route

Excreted principally in urine as inactive metabolites and small amounts (6%) of unchanged drug.^{211 212}

Half-life

Approximately 2.7–3.5 hours (in adults) or 8.1 hours (in neonates).^{211 212}

Special Populations

Decreased total plasma clearance in geriatric patients.²¹¹

Stability

Storage

Parenteral

Injection

20–25°C.^{211 212 215} If preparation contains epinephrine, protect from light.^{211 215}

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility^HID

Compatible
Sodium chloride 0.9%

Drug Compatibility

Do not mix with other local anesthetics (insufficient clinical data).^{211 212}

Admixture CompatibilityHID

Compatible
Buprenorphine HCl
Clonidine HCl with fentanyl citrate
Clonidine HCI with morphine sulfate
Fentanyl citrate
Hydromorphone HCl
Morphine HCl
Morphine sulfate
Sufentanil citrate

Syringe CompatibilityHID

Compatible
Clonidine HCl with fentanyl citrate
Clonidine HCl with morphine sulfate
Hydromorphone HCl
Morphine sulfate
Variable
Sodium bicarbonate

ActionsActions

• 
  

  Local anesthetics block the generation and conduction of nerve impulses by increasing the threshold for electrical excitation, slowing the propagation of the nerve impulse, and reducing the rate of rise of the action potential.^{211 212}

  
  


• 
  

  Bupivacaine exhibits analgesic effects that persist after return of sensation; thus need for strong analgesics is reduced.^{211 212}

  
  


• 
  

  Some preparations formulated with epinephrine to decrease bupivacaine’s rate and extent of systemic absorption and to prolong its duration of action.²¹¹

  
  


• 
  

  Has long duration of action.^{211 212}

  
  

Advice to Patients

• 
  

  Prior to administration, advise patients of the possibility of temporary loss of sensation and muscle function (e.g., in lower half of body following caudal, lumbar epidural, or subarachnoid block).^{211 212}

  
  


• 
  

  Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., cardiovascular or liver disease).^{211 212}

  
  


• 
  

  Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.^{211 212}

  
  


• 
  

  Importance of informing patients of other important precautionary information.^{211 212} (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Bupivacaine Hydrochloride

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection	0.25%*	Bupivacaine Hydrochloride Injection
			Marcaine Hydrochloride	Hospira
			Sensorcaine	APP Pharmaceuticals
			Sensorcaine-MPF	APP Pharmaceuticals
		0.5%*	Bupivacaine Hydrochloride Injection
			Marcaine Hydrochloride	Hospira
			Sensorcaine	APP Pharmaceuticals
			Sensorcaine-MPF	APP Pharmaceuticals
		0.75%*	Bupivacaine Hydrochloride Injection
			Marcaine Hydrochloride	Hospira
			Sensorcaine-MPF	APP Pharmaceuticals

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Bupivacaine Hydrochloride in Dextrose

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection	0.75% in 8.25% Dextrose*	Bupivacaine Spinal
			Marcaine Spinal	Hospira
			Sensorcaine-MPF Spinal	APP Pharmaceuticals

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Bupivacaine Hydrochloride Combinations

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection	0.25% with Epinephrine Bitartrate 1:200,000 (of epinephrine)*	Bupivacaine Hydrochloride and Epinephrine
			Marcaine Hydrochloride with Epinephrine	Hospira
			Sensorcaine with Epinephrine	APP Pharmaceuticals
			Sensorcaine-MPF with Epinephrine	APP Pharmaceuticals
		0.5% with Epinephrine Bitartrate 1:200,000 (of epinephrine)*	Bupivacaine Hydrochloride and Epinephrine
			Marcaine Hydrochloride with Epinephrine	Hospira
			Sensorcaine with Epinephrine	APP Pharmaceuticals
			Sensorcaine-MPF with Epinephrine	APP Pharmaceuticals
		0.75% with Epinephrine Bitartrate 1:200,000 (of epinephrine)	Sensorcaine-MPF with Epinephrine	APP Pharmaceuticals

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions February 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

200. Food and Drug Administration. Information for healthcare professionals: Chondrolysis reported with continuously infused local anesthetics (marketed as bupivacaine, chloroprocaine, lidocaine, mepivacaine, procaine, and ropivacaine). Rockville, MD; Updated 2010 Feb 16. From FDA website ().

201. Todd JF. Chondrolysis linked to intra-articular infusions. Medical Devices Alerts and Notices. Silver Spring, MD: Food and Drug Administration; 2010 June. From FDA website ().

202. Hansen BP, Beck CL, Beck EP et al. Postarthroscopic glenohumeral chondrolysis. Am J Sports Med. 2007; 35:1628-34. [PubMed 17609526]

203. Bailie DS, Ellenbecker TS. Severe chondrolysis after shoulder arthroscopy: a case series. J Shoulder Elbow Surg. 2009 Sep-Oct; 18:742-7.

204. Anakwenze OA, Hosalkar H, Huffman GR. Case Reports: Two Cases of Glenohumeral Chondrolysis after Intraarticular Pain Pumps. Clin Orthop Relat Res. 2010; :.

205. Anderson SL, Buchko JZ, Taillon MR et al. Chondrolysis of the glenohumeral joint after infusion of bupivacaine through an intra-articular pain pump catheter: a report of 18 cases. Arthroscopy. 2010; 26:451-61. [PubMed 20362823]

206. Rapley JH, Beavis RC, Barber FA. Glenohumeral chondrolysis after shoulder arthroscopy associated with continuous bupivacaine infusion. Arthroscopy. 2009; 25:1367-73. [PubMed 19962061]

207. Scheffel PT, Clinton J, Lynch JR et al. Glenohumeral chondrolysis: A systematic review of 100 cases from the English language literature. J Shoulder Elbow Surg. 2010; :. [PubMed 20421168]

208. Ballieul RJ, Jacobs TF, Herregods S et al. The peri-operative use of intra-articular local anesthetics: a review. Acta Anaesthesiol Belg. 2009; 60:101-8. [PubMed 19594092]

209. Busfield BT, Romero DM. Pain pump use after shoulder arthroscopy as a cause of glenohumeral chondrolysis. Arthroscopy. 2009; 25:647-52. [PubMed 19501296]

211. APP Pharmaceuticals. Sensorcaine (bupivacaine hydrochloride injection, USP), Sensorcaine-MPF (bupivacaine hydrochloride injection, USP), Sensorcaine with epinephrine (bupivacaine hydrochloride and epinephrine injection, USP), and Sensorcaine-MPF with epinephrine (bupivacaine hydrochloride and epinephrine injection, USP) prescribing information. Schaumburg, IL; 2010 Feb.

212. APP Pharmaceuticals. Sensorcaine-MPF spinal injection (bupivacaine hydrochloride in dextrose injection, USP) prescribing information. Schaumburg, IL; 2010 Feb.

213. Hospira. Marcaine (bupivacaine hydrochloride injection, USP), Marcaine with epinephrine (bupivacaine hydrochloride and epinephrine injection, USP) prescribing information. Lake Forest, IL; 2009 Nov.

214. Hospira. Marcaine Spinal (bupivacaine hydrochloride in dextrose injection, USP) prescribing information. Lake Forest, IL; 2009 Nov.

215. Hospira. Bupivacaine hydrochloride and epinephrine injection prescribing information. Lake Forest, IL; 2006 Nov.

a. AHFS drug information 2011. McEvoy GK, ed. Bupivacaine Hydrochloride. Bethesda, MD: American Society of Health-System Pharmacists; 2011; e-pub ahead of print.

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:225-9.

More Bupivacaine Hydrochloride resources

• Bupivacaine Hydrochloride Use in Pregnancy & Breastfeeding
• Bupivacaine Hydrochloride Drug Interactions
• Bupivacaine Hydrochloride Support Group
• 2 Reviews for Bupivacaine Hydrochloride - Add your own review/rating

• Bupivacaine Prescribing Information (FDA)


• Bupivacaine Solution MedFacts Consumer Leaflet (Wolters Kluwer)


• bupivacaine Concise Consumer Information (Cerner Multum)


• Marcaine Spinal Solution MedFacts Consumer Leaflet (Wolters Kluwer)


• Marcaine Spinal Prescribing Information (FDA)


• Sensorcaine Prescribing Information (FDA)

Compare Bupivacaine Hydrochloride with other medications

• Cesarean Section
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• Postoperative Pain

Ranitidina Alpharma

Ranitidina Alpharma may be available in the countries listed below.

Ingredient matches for Ranitidina Alpharma

Ranitidine

Ranitidine hydrochloride (a derivative of Ranitidine) is reported as an ingredient of Ranitidina Alpharma in the following countries:

• Portugal

International Drug Name Search

Ninobarucin

Ninobarucin may be available in the countries listed below.

Ingredient matches for Ninobarucin

Nisoldipine

Nisoldipine is reported as an ingredient of Ninobarucin in the following countries:

• Japan

International Drug Name Search

Thiocolchicoside EG

Thiocolchicoside EG may be available in the countries listed below.

Ingredient matches for Thiocolchicoside EG

Thiocolchicoside

Thiocolchicoside is reported as an ingredient of Thiocolchicoside EG in the following countries:

• France

International Drug Name Search

Ranitab

Ranitab may be available in the countries listed below.

Ingredient matches for Ranitab

Ranitidine

Ranitidine hydrochloride (a derivative of Ranitidine) is reported as an ingredient of Ranitab in the following countries:

• Ecuador


• Germany


• Turkey

International Drug Name Search

Ritonavir

In the US, Ritonavir (ritonavir systemic) is a member of the drug class protease inhibitors and is used to treat HIV Infection.

US matches:

• Ritonavir


• Ritonavir Capsules


• Ritonavir Solution

Scheme

Rec.INN

ATC (Anatomical Therapeutic Chemical Classification)

J05AE03

CAS registry number (Chemical Abstracts Service)

0155213-67-5

Chemical Formula

C37-H48-N6-O5-S2

Molecular Weight

720

Therapeutic Category

Antiviral agent, HIV protease inhibitor

Chemical Name

5-Thiazolylmethyl [(αS)-α-[(1S,3S)-1-hydroxy-3-[(2S)-2-[3-[(2-isopropyl-4-thiazolyl)methyl]-3-methylureido]-3-methylbutyramido]-4-phenylbutyl]phenethyl]carbamate

Foreign Names

• Ritonavirum (Latin)
• Ritonavir (German)
• Ritonavir (French)
• Ritonavir (Spanish)

Generic Names

• Ritonavir (OS: USAN, BAN)
• Abbott-84538 (IS)
• ABT 538 (IS)
• Ritonavir (PH: Ph. Eur. 6, USP 32, Ph. Int. 4, BP 2010)
• Ritonavirum (PH: Ph. Eur. 6, Ph. Int. 4)

Brand Names

• Aluvia (Ritonavir and Lopinavir)
  Abbott, South Africa



• Kaletra (Ritonavir and Lopinavir)
  Abbott, United Arab Emirates; Abbott, Antigua & Barbuda; Abbott, Netherlands Antilles; Abbott, Australia; Abbott, Aruba; Abbott, Aruba; Abbott, Bosnia & Herzegowina; Abbott, Barbados; Abbott, Belgium; Abbott, Bahrain; Abbott, Bermuda; Abbott, Bahamas; Abbott, Canada; Abbott, Switzerland; Abbott, Chile; Abbott, Colombia; Abbott, Costa Rica; Abbott, Czech Republic; Abbott, Germany; Abbott, Denmark; Abbott, Ecuador; Abbott, Egypt; Abbott, Spain; Abbott, Finland; Abbott, France; Abbott, United Kingdom; Abbott, Grenada; Abbott, Georgia; Abbott, Greece; Abbott, Guatemala; Abbott, Guyana; Abbott, Hong Kong; Abbott, Croatia (Hrvatska); Abbott, Haiti; Abbott, Hungary; Abbott, Israel; Abbott, Iraq; Abbott, Iran; Abbott, Italy; Abbott, Jamaica; Abbott, Jordan; Abbott, Japan; Abbott, Kuwait; Abbott, Cayman Islands; Abbott, Lebanon; Abbott, Saint Lucia; Abbott, Luxembourg; Abbott, Malaysia; Abbott, Nicaragua; Abbott, Netherlands; Abbott, Norway; Abbott, New Zealand; Abbott, Panama; Abbott, Peru; Abbott, Poland; Abbott, Portugal; Abbott, Qatar; Abbott, Serbia; Abbott, Russian Federation; Abbott, Saudi Arabia; Abbott, Sweden; Abbott, Singapore; Abbott, Slovenia; Abbott, Slovakia; Abbott, Suriname; Abbott, El Salvador; Abbott, Syria; Abbott, Turks & Caicos Islands; Abbott, Thailand; Abbott, Tunisia; Abbott, Turkey; Abbott, Trinidad & Tobago; Abbott, Taiwan; Abbott, United States; Abbott, Saint Vincent & The Grenadines; Abbott, Venezuela; Abbott, Virgin Islands (British); Abbott, Yemen; Abbott, South Africa; Abbott Laboratories, Austria; Abbott Laboratories, Ethiopia; Cardinal Health, Oman



• Lopivir Plus (Ritonavir and Lopinavir)
  Grey Inversiones, Peru



• Norvir
  Abbott, United Arab Emirates; Abbott, Australia; Abbott, Belgium; Abbott, Bahrain; Abbott, Canada; Abbott, Switzerland; Abbott, Chile; Abbott, Colombia; Abbott, Costa Rica; Abbott, Czech Republic; Abbott, Germany; Abbott, Denmark; Abbott, Ecuador; Abbott, Egypt; Abbott, Spain; Abbott, Finland; Abbott, France; Abbott, United Kingdom; Abbott, Greece; Abbott, Guatemala; Abbott, Hong Kong; Abbott, Honduras; Abbott, Hungary; Abbott, Indonesia; Abbott, Israel; Abbott, Iraq; Abbott, Iran; Abbott, Iceland; Abbott, Italy; Abbott, Jordan; Abbott, Japan; Abbott, Kuwait; Abbott, Lebanon; Abbott, Luxembourg; Abbott, Malaysia; Abbott, Nicaragua; Abbott, Netherlands; Abbott, Norway; Abbott, New Zealand; Abbott, Oman; Abbott, Panama; Abbott, Peru; Abbott, Poland; Abbott, Qatar; Abbott, Romania; Abbott, Serbia; Abbott, Saudi Arabia; Abbott, Sweden; Abbott, Slovakia; Abbott, El Salvador; Abbott, Syria; Abbott, Thailand; Abbott, Turkey; Abbott, Taiwan; Abbott, United States; Abbott, Venezuela; Abbott, Yemen; Abbott, South Africa; Abbott Laboratories, Austria; Amgen, Slovenia



• Ritomune
  Cipla, Georgia; Cipla, India



• Ritonavir Abbott
  Abbott, Argentina



• Ritonavir
  Abbott, United States



• Ritonax
  Biotoscana, Colombia



• Virtina
  Biogen, Colombia

International Drug Name Search

Glossary

BAN	British Approved Name
IS	Inofficial Synonym
OS	Official Synonym
PH	Pharmacopoeia Name
Rec.INN	Recommended International Nonproprietary Name (World Health Organization)
USAN	United States Adopted Name

Click for further information on drug naming conventions and International Nonproprietary Names.

Itrareel

Itrareel may be available in the countries listed below.

Ingredient matches for Itrareel

Itraconazole

Itraconazole is reported as an ingredient of Itrareel in the following countries:

• Japan

International Drug Name Search

Dolaxen

Dolaxen may be available in the countries listed below.

Ingredient matches for Dolaxen

Naproxen

Naproxen is reported as an ingredient of Dolaxen in the following countries:

• Peru

International Drug Name Search

Pravaselect

Pravaselect may be available in the countries listed below.

Ingredient matches for Pravaselect

Pravastatin

Pravastatin sodium salt (a derivative of Pravastatin) is reported as an ingredient of Pravaselect in the following countries:

• Italy

International Drug Name Search

Tham

Tham is a brand name of tromethamine, approved by the FDA in the following formulation(s):

THAM (tromethamine - injectable; injection)

• 
  Manufacturer: HOSPIRA
  
  Approved Prior to Jan 1, 1982
  
  Strength(s): 3.6GM/100ML ^[RLD]

Has a generic version of Tham been approved?

No. There is currently no therapeutically equivalent version of Tham available.

Note: Fraudulent online pharmacies may attempt to sell an illegal generic version of Tham. These medications may be counterfeit and potentially unsafe. If you purchase medications online, be sure you are buying from a reputable and valid online pharmacy. Ask your health care provider for advice if you are unsure about the online purchase of any medication.

See also: About generic drugs.

Related Patents

There are no current U.S. patents associated with Tham.

See also...

• Tham Consumer Information (Cerner Multum)
• Tham AHFS DI Monographs (ASHP)
• Tromethamine Consumer Information (Cerner Multum)
• Tromethamine AHFS DI Monographs (ASHP)

Prazil

Prazil may be available in the countries listed below.

In some countries, this medicine may only be approved for veterinary use.

Ingredient matches for Prazil

Sulfadimethoxine

Sulfadimethoxine is reported as an ingredient of Prazil in the following countries:

• Italy

Trimethoprim

Trimethoprim is reported as an ingredient of Prazil in the following countries:

• Italy

International Drug Name Search

Zorac

Zorac may be available in the countries listed below.

UK matches:

• Zorac
• Zorac 0.05% Gel (SPC)
• Zorac 0.1% Gel (SPC)

Ingredient matches for Zorac

Tazarotene

Tazarotene is reported as an ingredient of Zorac in the following countries:

• Australia


• Belgium


• Croatia (Hrvatska)


• France


• Greece


• Italy


• Luxembourg


• Poland


• Serbia


• South Africa


• Spain


• Taiwan


• United Kingdom

International Drug Name Search

Glossary

SPC	Summary of Product Characteristics (UK)

Click for further information on drug naming conventions and International Nonproprietary Names.

Ramivan

Ramivan may be available in the countries listed below.

Ingredient matches for Ramivan

Roxithromycin

Roxithromycin is reported as an ingredient of Ramivan in the following countries:

• Chile

International Drug Name Search

Kaldyum

Kaldyum may be available in the countries listed below.

Ingredient matches for Kaldyum

Potassium Chloride

Potassium Chloride is reported as an ingredient of Kaldyum in the following countries:

• Hungary


• Poland


• Slovakia

International Drug Name Search

Randum

Randum may be available in the countries listed below.

Ingredient matches for Randum

Metoclopramide

Metoclopramide hydrochloride (a derivative of Metoclopramide) is reported as an ingredient of Randum in the following countries:

• Italy

International Drug Name Search

Butalbital,Aspirin and Caffeine Capsule

Butalbital, Aspirin, and Caffeine Capsules CIII

Rx Only

Butalbital,Aspirin and Caffeine Capsule Description

Each butalbital, aspirin, and caffeine capsule for oral administration contains: butalbital, USP, 50 mg; aspirin, USP, 325 mg; caffeine, USP, 40 mg.

Butalbital (5-allyl-5-isobutylbarbituric acid) is a short- to intermediate-acting barbiturate. It has the following structural formula:

Aspirin (benzoic acid, 2-(acetyloxy)-) is an analgesic, antipyretic, and anti-inflammatory. It has the following structural formula:

Caffeine (1, 3, 7-trimethylxanthine) is a central nervous system stimulant. It has the following structural formula:

Active Ingredients: aspirin, USP, butalbital, USP, and caffeine, USP.

Inactive Ingredients: pregelatinized starch, microcrystalline cellulose, sodium starch glyco­late, trimyristin, talc, colloidal silicon dioxide, D&C Yellow No. 10, FD&C Green No. 3, and gelatin. The capsule imprinting ink contains: shellac glaze in ethanol, iron oxide black, n-butyl alcohol, propylene glycol, ethanol, methanol, FD&C Blue No. 2 Aluminum Lake, FD&C Red No. 40 Aluminum Lake, FD&C Blue No. 1 Aluminum Lake, and D&C Yellow No. 10 Aluminum Lake.

Butalbital,Aspirin and Caffeine Capsule - Clinical Pharmacology

Pharmacologically, butalbital, aspirin, and caffeine capsules combine the analgesic properties of aspirin with the anxiolytic and muscle relaxant properties of butalbital.

The clinical effectiveness of butalbital, aspirin, and caffeine capsules in tension headache has been established in double-blind, placebo-controlled, multi-clinic trials. A factorial design study compared butalbital, aspirin, and caffeine capsules with each of its major components. This study demonstrated that each component contributes to the efficacy of butalbital, aspirin, and caffeine capsules in the treatment of the target symptoms of tension headache (headache pain, psychic tension, and muscle contraction in the head, neck, and shoulder region). For each symptom and the symptom complex as a whole, butalbital, aspirin, and caffeine capsules were shown to have significantly superior clinical effects to either component alone.

Pharmacokinetics

The behavior of the individual components is described below.

Aspirin

The systemic availability of aspirin after an oral dose is highly dependent on the dosage form, the presence of food, the gastric emptying time, gastric pH, antacids, buffering agents, and particle size. These factors affect not necessarily the extent of absorption of total salicylates but more the stability of aspirin prior to absorption.

During the absorption process and after absorption, aspirin is mainly hydrolyzed to salicylic acid and distributed to all body tissues and fluids, including fetal tissues, breast milk, and the central nervous system (CNS). Highest concentrations are found in plasma, liver, renal cortex, heart, and lung. In plasma, about 50% to 80% of the salicylic acid and its metabolites are loosely bound to plasma proteins.

The clearance of total salicylates is subject to saturable kinetics; however, first-order elimination kinetics are still a good approximation for doses up to 650 mg. The plasma half-life for aspirin is about 12 minutes and for salicylic acid and/or total salicylates is about 3.0 hours.

The elimination of therapeutic doses is through the kidneys either as salicylic acid or other biotransformation products. The renal clearance is greatly augmented by an alkaline urine as is produced by concurrent administration of sodium bicarbonate or potassium citrate.

The biotransformation of aspirin occurs primarily in the hepatocytes. The major metabolites are salicyluric acid (75%), the phenolic and acyl glucuronides of salicylate (15%), and gentisic and gentisuric acid (1%). The bioavailability of the aspirin component of butalbital, aspirin, and caffeine capsules is equivalent to that of a solution except for a slower rate of absorption. A peak concentration of 8.80 mcg/mL was obtained at 40 minutes after a 650 mg dose.

See OVERDOSAGE for toxicity information.

Butalbital

Butalbital is well absorbed from the gastrointestinal tract and is expected to distribute to most of the tissues in the body. Barbiturates, in general, may appear in breast milk and readily cross the placental barrier. They are bound to plasma and tissue proteins to a varying degree and binding increases directly as a function of lipid solubility.

Elimination of butalbital is primarily via the kidney (59% to 88% of the dose) as unchanged drug or metabolites. The plasma half-life is about 35 hours. Urinary excretion products included parent drug (about 3.6% of the dose), 5-isobutyl-5-(2,3-dihydroxypropyl) barbituric acid (about 24% of the dose), 5-allyl-5(3-hydroxy-2-methyl-1-propyl) barbituric acid (about 4.8% of the dose), products with the barbituric acid ring hydrolyzed with excretion of urea (about 14% of the dose), as well as unidentified materials. Of the material excreted in the urine, 32% was conjugated.

The bioavailability of the butalbital component of butalbital, aspirin, and caffeine capsules is equivalent to that of a solution except for a decrease in the rate of absorption. A peak concentration of 2,020 ng/mL is obtained at about 1.5 hours after a 100 mg dose. The in vitro plasma protein binding of butalbital is 45% over the concentration range of 0.5 to 20 mcg/mL.

This falls within the range of plasma protein binding (20% to 45%) reported with other barbiturates such as phenobarbital, pentobarbital, and secobarbital sodium. The plasma-to-blood concentration ratio was almost unity indicating that there is no preferential distribution of butalbital into either plasma or blood cells.

See OVERDOSAGE for toxicity information.

Caffeine

Like most xanthines, caffeine is rapidly absorbed and distributed in all body tissues and fluids, including the CNS, fetal tissues, and breast milk.

Caffeine is cleared rapidly through metabolism and excretion in the urine. The plasma half-life is about 3.0 hours. Hepatic biotransformation prior to excretion results in about equal amounts of 1-methylxanthine and 1-methyluric acid. Of the 70% of the dose that has been recovered in the urine, only 3% was unchanged drug.

The bioavailability of the caffeine component for butalbital, aspirin, and caffeine capsules is equivalent to that of a solution except for a slightly longer time to peak. A peak concentration of 1,660 ng/mL was obtained in less than an hour for an 80 mg dose.

See OVERDOSAGE for toxicity information.

Indications and Usage for Butalbital,Aspirin and Caffeine Capsule

Butalbital, aspirin, and caffeine capsules are indicated for the relief of the symptom complex of tension (or muscle contraction) headache. Evidence supporting the efficacy and safety of butalbital, aspirin, and caffeine capsules in the treatment of multiple recurrent headaches is unavailable. Caution in this regard is required because butalbital is habit-forming and potentially abusable.

Contraindications

Butalbital, aspirin, and caffeine capsules are contraindicated under the following conditions:

1. Hypersensitivity or intolerance to aspirin, caffeine, or butalbital.


2. Patients with a hemorrhagic diathesis (e.g., hemophilia, hypoprothrombinemia, von Willebrand's disease, the thrombocytopenias, thrombasthenia and other ill-defined hereditary platelet dysfunctions, severe vitamin K deficiency and severe liver damage).


3. Patients with the syndrome of nasal polyps, angioedema and bronchospastic reactivity to aspirin or other nonsteroidal anti-inflammatory drugs. Anaphylactoid reactions have occurred in such patients.


4. Peptic ulcer or other serious gastrointestinal lesions.


5. Patients with porphyria.

Warnings

Therapeutic doses of aspirin can cause anaphylactic shock and other severe allergic reactions. It should be ascertained if the patient is allergic to aspirin, although a specific history of allergy may be lacking.

Significant bleeding can result from aspirin therapy in patients with peptic ulcer or other gastrointestinal lesions, and in patients with bleeding disorders. Aspirin administered preoperatively may prolong the bleeding time. Butalbital is habit-forming and potentially abusable. Consequently, the extended use of butalbital, aspirin, and caffeine capsules is not recommended. Results from epidemiologic studies indicate an association between aspirin and Reye's Syndrome. Caution should be used in administering this product to children, including teenagers, with chicken pox or flu.

Precautions

General

Butalbital, aspirin, and caffeine capsules should be prescribed with caution for certain special-risk patients such as the elderly or debilitated, and those with severe impairment of renal or hepatic function, coagulation disorders, head injuries, elevated intracranial pressure, acute abdominal conditions, hypothyroidism, urethral stricture, Addison's disease, or prostatic hypertrophy.

Aspirin should be used with caution in patients on anticoagulant therapy and in patients with underlying hemostatic defects, and extreme caution in the presence of peptic ulcer.

Precautions should be taken when administering salicylates to persons with known allergies. Hypersensitivity to aspirin is particularly likely in patients with nasal polyps, and relatively common in those with asthma.

Information for Patients

Patients should be informed that butalbital, aspirin, and caffeine capsules contain aspirin and should not be taken by patients with an aspirin allergy.

Butalbital, aspirin, and caffeine capsules may impair the mental and/or physical abilities required for performance of potentially hazardous tasks such as driving a car or operating machinery. Such tasks should be avoided while taking butalbital, aspirin, and caffeine capsules.

Alcohol and other CNS depressants may produce an additive CNS depression when taken with butalbital, aspirin, and caffeine capsules and should be avoided.

Butalbital may be habit-forming. Patients should take the drug only for as long as it is prescribed, in the amounts prescribed, and no more frequently than prescribed.

Laboratory Tests

In patients with severe hepatic or renal disease, effects of therapy should be monitored with serial liver and/or renal function tests.

Drug Interactions

The CNS effects of butalbital may be enhanced by monoamine oxidase (MAO) inhibitors.

In patients receiving concomitant corticosteroids and chronic use of aspirin, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.

Butalbital, aspirin, and caffeine capsules may enhance the effects of:

1. Oral anticoagulants, causing bleeding by inhibiting prothrombin formation in the liver and displacing anticoagulants from plasma protein binding sites.


2. Oral antidiabetic agents and insulin, causing hypoglycemia by contributing an additive effect, if dosage of butalbital, aspirin, and caffeine capsules exceeds maximum recommended daily dosage.


3. 6-mercaptopurine and methotrexate, causing bone marrow toxicity and blood dyscrasias by displacing these drugs from secondary binding sites, and, in the case of methotrexate, also reducing its excretion.


4. Non-steroidal anti-inflammatory agents, increasing the risk of peptic ulceration and bleeding by contributing additive effects.


5. Other narcotic analgesics, alcohol, general anesthetics, tranquilizers such as chlordiazepoxide, sedative-hypnotics, or other CNS depressants, causing increased CNS depression.

Butalbital, aspirin, and caffeine capsules may diminish the effects of:

Uricosuric agents such as probenecid and sulfinpyrazone, reducing their effectiveness in the treatment of gout. Aspirin competes with these agents for protein binding sites.

Drug/Laboratory Test Interactions

Aspirin: Aspirin may interfere with the following laboratory determinations in blood: serum amylase, fasting blood glucose, cholesterol, protein, serum glutamic-oxaloacetic transaminase (SGOT), uric acid, prothrombin time and bleeding time. Aspirin may interfere with the following laboratory determinations in urine: glucose, 5-hydroxyindoleacetic acid, Gerhardt ketone, vanillylmandelic acid (VMA), uric acid, diacetic acid, and spectrophotometric detection of barbiturates.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Adequate long-term studies have been conducted in mice and rats with aspirin, alone or in combination with other drugs, in which no evidence of carcinogenesis was seen. No adequate studies have been conducted in animals to determine whether aspirin has a potential for mutagenesis or impairment of fertility. No adequate studies have been conducted in animals to determine whether butalbital has a potential for carcinogenesis, mutagenesis, or impairment of fertility.

Usage in Pregnancy

Teratogenic Effects

Pregnancy Category C. Animal reproduction studies have not been conducted with butalbital, aspirin, and caffeine capsules. It is also not known whether butalbital, aspirin, and caffeine capsules can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Butalbital, aspirin, and caffeine capsules should be given to a pregnant woman only when clearly needed.

Nonteratogenic Effects

Withdrawal seizures were reported in a two-day-old male infant whose mother had taken a butalbital-containing drug during the last 2 months of pregnancy. Butalbital was found in the infant's serum. The infant was given phenobarbital 5 mg/kg, which was tapered without further seizure or other withdrawal symptoms.

Studies of aspirin use in pregnant women have not shown that aspirin increases the risk of abnormalities when administered during the first trimester of pregnancy. In controlled studies involving 41,337 pregnant women and their offspring, there was no evidence that aspirin taken during pregnancy caused stillbirth, neonatal death or reduced birth weight. In controlled studies of 50,282 pregnant women and their offspring, aspirin administration in moderate and heavy doses during the first four lunar months of pregnancy showed no teratogenic effect.

Therapeutic doses of aspirin in pregnant women close to term may cause bleeding in mother, fetus, or neonate. During the last 6 months of pregnancy, regular use of aspirin in high doses may prolong pregnancy and delivery.

Labor and Delivery

Ingestion of aspirin prior to delivery may prolong delivery or lead to bleeding in the mother or neonate.

Nursing Mothers

Aspirin, caffeine, and barbiturates are excreted in breast milk in small amounts, but the significance of their effects on nursing infants is not known. Because of potential for serious adverse reactions in nursing infants from butalbital, aspirin, and caffeine capsules, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Adverse Reactions

The most frequent adverse reactions are drowsiness and dizziness. Less frequent adverse reactions are lightheadedness and gastrointestinal disturbances including nausea, vomiting, and flatulence. A single incidence of bone marrow suppression has been reported with the use of butalbital, aspirin, and caffeine capsules. Several cases of dermatological reactions including toxic epidermal necrolysis and erythema multiforme have been reported.

Drug Abuse and Dependence

Controlled Substance

Butalbital, aspirin, and caffeine capsules are controlled by the Drug Enforcement Administration and are classified under Schedule III.

Abuse and Dependence

Butalbital

Barbiturates may be habit-forming: Tolerance, psychological dependence, and physical dependence may occur especially following prolonged use of high doses of barbiturates. The average daily dose for the barbiturate addict is usually about 1,500 mg. As tolerance to barbiturates develops, the amount needed to maintain the same level of intoxication increases; tolerance to a fatal dosage, however, does not increase more than two-fold. As this occurs, the margin between an intoxication dosage and fatal dosage becomes smaller. The lethal dose of a barbiturate is far less if alcohol is also ingested. Major withdrawal symptoms (convulsions and delirium) may occur within 16 hours and last up to 5 days after abrupt cessation of these drugs. Intensity of withdrawal symptoms gradually declines over a period of approximately 15 days. Treatment of barbiturate dependence consists of cautious and gradual withdrawal of the drug. Barbiturate-dependent patients can be withdrawn by using a number of different withdrawal regimens. One method involves initiating treatment at the patient's regular dosage level and gradually decreasing the daily dosage as tolerated by the patient.

Overdosage

The toxic effects of acute overdosage of butalbital, aspirin, and caffeine capsules are attributable mainly to its barbiturate component, and, to a lesser extent, aspirin. Because toxic effects of caffeine occur in very high dosages only, the possibility of significant caffeine toxicity from butalbital, aspirin, and caffeine capsules overdosage is unlikely.

Signs and Symptoms

Symptoms attributable to acute barbiturate poisoning include drowsiness, confusion, and coma; respiratory depression; hypotension; hypovolemic shock. Symptoms attributable to acute aspirin poisoning include hyperpnea; acid-base disturbances with development of metabolic acidosis; vomiting and abdominal pain; tinnitus; hyperthermia; hypoprothrombinemia; restlessness; delirium; convulsions. Acute caffeine poisoning may cause insomnia, restlessness, tremor, and delirium; tachycardia and extrasystoles.

Treatment

Treatment consists primarily of management of barbiturate intoxication and the correction of the acid-base imbalance due to salicylism. Vomiting should be induced mechanically or with emetics in the conscious patient. Gastric lavage may be used if the pharyngeal and laryngeal reflexes are present and if less than 4 hours have elapsed since ingestion. A cuffed endotracheal tube should be inserted before gastric lavage of the unconscious patient and when necessary to provide assisted respiration. Diuresis, alkalinization of the urine, and correction of electrolyte disturbances should be accomplished through administration of intravenous fluids such as 1% sodium bicarbonate in 5% dextrose in water. Meticulous attention should be given to maintaining adequate pulmonary ventilation. The value of vasopressor agents such as Norepinephrine or Phenylephrine Hydrochloride in treating hypotension is questionable since they increase vasoconstriction and decrease blood flow. However, if prolonged support of blood pressure is required, Norepinephrine Bitartrate (Levophed®)1 may be given I.V. with the usual precautions and serial blood pressure monitoring. In severe cases of intoxication, peritoneal dialysis, hemodialysis, or exchange transfusion may be lifesaving. Hypoprothrombinemia should be treated with Vitamin K, intravenously.

Up-to-date information about the treatment of overdose can often be obtained from a Certified Regional Poison Control Center. Telephone numbers of Certified Regional Poison Control Centers are listed in the Physicians' Desk Reference®2.

Toxic and Lethal Doses (for adults)

Butalbital: toxic dose 1 g (20 capsules of butalbital, aspirin, and caffeine)

Aspirin: toxic blood level greater than 30 mg/100 mL; lethal dose 10 to 30 g

Caffeine: toxic dose 1 g (25 capsules of butalbital, aspirin, and caffeine)

1

Levophed is a registered Trademark of Sanofi Winthrop Pharmaceuticals.

2

Trademark of Medical Economics Company, Inc.

Butalbital,Aspirin and Caffeine Capsule Dosage and Administration

One or 2 capsules every 4 hours. Total daily dose should not exceed 6 capsules. Extended and repeated use of this product is not recommended because of the potential for physical dependence.

How is Butalbital,Aspirin and Caffeine Capsule Supplied

Butalbital, aspirin, and caffeine capsules are dark green and light green in color, imprinted with logo "LANNETT" on the cap and "1552" on the body. Each capsule contains: butalbital USP, 50 mg; aspirin USP, 325 mg; caffeine USP, 40 mg and is available as follows:

Bottles of 100   NDC 0527-1552-01

Dispense in a tight container as defined in the USP. Use child-resistant closure. Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

Protect from moisture.

Manufactured by:

Lannett Company, Inc.

Philadelphia, PA 19136

Made in the USA

10-917

Rev. 10/10; Revision 1

PRINCIPAL DISPLAY PANEL

NDC 0527-1552-01

Lannett

BUTALBITAL,

ASPIRIN, AND

CAFFEINE

CAPSULES

CIII

50 mg/325 mg/40 mg

Rx Only

100 CAPSULES

BUTALBITAL, ASPIRIN, AND CAFFEINE  butalbital, aspirin, and caffeine  capsule

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0527-1552 Route of Administration ORAL DEA Schedule CIII

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength BUTALBITAL (BUTALBITAL) BUTALBITAL 50 mg ASPIRIN (ASPIRIN) ASPIRIN 325 mg CAFFEINE (CAFFEINE) CAFFEINE 40 mg

Inactive Ingredients Ingredient Name Strength STARCH, PREGELATINIZED CORN   CELLULOSE, MICROCRYSTALLINE   SODIUM STARCH GLYCOLATE TYPE A POTATO   TRIMYRISTIN   TALC   COLLOIDAL SILICON DIOXIDE   D&C YELLOW NO. 10   FD&C GREEN NO. 3   GELATIN   SHELLAC   ALCOHOL   FERROSOFERRIC OXIDE   BUTYL ALCOHOL   PROPYLENE GLYCOL   METHYL ALCOHOL   FD&C BLUE NO. 2   ALUMINUM OXIDE   FD&C RED NO. 40   FD&C BLUE NO. 1

Product Characteristics Color GREEN (dark green and light green) Score no score Shape CAPSULE Size 22mm Flavor Imprint Code Lannett;1552 Contains

Packaging # NDC Package Description Multilevel Packaging 1 0527-1552-01 100 CAPSULE In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA086996	10/11/1985

Labeler - Lannett Company, Inc. (002277481)

Establishment
Name	Address	ID/FEI	Operations
Lannett Company, Inc.		002277481	MANUFACTURE

Establishment
Name	Address	ID/FEI	Operations
Lannett Company, Inc.		829757603	ANALYSIS, LABEL, MANUFACTURE, PACK

Revised: 11/2010Lannett Company, Inc.

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