Rispaxol

Rispaxol may be available in the countries listed below.

Ingredient matches for Rispaxol

Risperidone

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

• Latvia

International Drug Name Search

Calcium Phosphate

Scheme

Ph. Eur.

ATC (Anatomical Therapeutic Chemical Classification)

A12AA01

CAS registry number (Chemical Abstracts Service)

0007758-87-4

Chemical Formula

Ca3(P-O4)2 + Ca-H-P-O4

Therapeutic Categories

Pharmaceutic aid

Antacid

Mineral supplement

Chemical Name

Calcium phosphate (3:2) mixture with calcium phosphate (1:1)

Foreign Names

• Tricalcii phosphas (Latin)
• Tricalciumphospat (German)
• Phosphate tricalcique (French)
• Calcio, fosfato de (Spanish)

Generic Names

• CCRIS 3668 (IS)
• E 341 (IS)
• Tribasic Calcium Phosphate (IS: BP, Ph. Int.)
• Tricalcium bisorthophosphat (IS)
• Tricalcium diorthophosphate (IS)
• Tricalciumbis (IS: phosphat)
• Tricalciumphosphate (IS)
• Calcium Hydrogen Phosphate Anhydrous (PH: BP 2010)
• Calcium Phosphate (PH: BP 2010)
• Calcium phosphate (PH: Ph. Eur. 6, Ph. Int. 4)
• Tribasic Calcium Phosphate (PH: NF 27)

Brand Names

• Calcio 20 Emulsion
  Madariaga, Spain



• Calcio 20 Fuerte (Calcium Phosphate and Colecalciferol)
  Madariaga, Spain



• Calcivit (Calcium Phosphate and Colecalciferol)
  UB Interpharm, Switzerland



• Caldetri (Calcium Phosphate and Colecalciferol)
  Global Multi Pharmalab, Indonesia



• Calfovit (Calcium Phosphate and Colecalciferol)
  A. Menarini, United Kingdom



• Cavea (Calcium Phosphate and Colecalciferol)
  Pharos, Indonesia



• Cavit D3 (Calcium Phosphate and Colecalciferol)
  Merck, Indonesia



• Decal (Calcium Phosphate and Colecalciferol)
  Menarini, Greece



• Decalcit (Calcium Phosphate and Colecalciferol)
  Geistlich, Switzerland



• Dumocalcin
  Actavis, Indonesia



• Foscald3 (Calcium Phosphate and Colecalciferol)
  Firma, Italy



• Neocalcit
  Biospray, Greece



• Osteofos (Calcium Phosphate and Colecalciferol)
  Menarini, Ireland; Menarini, Luxembourg; Menarini International-L, Italy



• Osteomerck (Calcium Phosphate and Colecalciferole)
  Merck, Spain



• Osteorel
  Uni-Pharma, Greece



• Ostram
  Merck Serono, France



• Ostram (Calcium Phosphate and Calcium Phosphate)
  Faes, Spain



• Ostram (Calcium Phosphate and Colecalciferol)
  Bracco, Italy



• Phytopharma Calcium (Calcium Phosphate and Colecalciferol)
  Phytopharma, Switzerland



• Vitacal (Calcium Phosphate and Colecalciferol)
  Menarini, Switzerland

International Drug Name Search

Glossary

BP	British Pharmacopoeia
IS	Inofficial Synonym
PH	Pharmacopoeia Name
Ph. Eur.	European Pharmacopoeia
Ph. Int.	Pharmacopoea Internationalis

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

LisiLich comp

LisiLich comp may be available in the countries listed below.

Ingredient matches for LisiLich comp

Hydrochlorothiazide

Hydrochlorothiazide is reported as an ingredient of LisiLich comp in the following countries:

• Germany

Lisinopril

Lisinopril dihydrate (a derivative of Lisinopril) is reported as an ingredient of LisiLich comp in the following countries:

• Germany

International Drug Name Search

Ortho Evra

In the US, Ortho Evra (ethinyl estradiol/norelgestromin systemic) is a member of the drug class contraceptives and is used to treat Birth Control.

US matches:

• Ortho Evra


• Ortho Evra Patch

Ingredient matches for Ortho Evra

Ethinylestradiol

Ethinylestradiol is reported as an ingredient of Ortho Evra in the following countries:

• United States

Norelgestromin

Norelgestromin is reported as an ingredient of Ortho Evra in the following countries:

• United States

International Drug Name Search

Perkapil

Perkapil may be available in the countries listed below.

Ingredient matches for Perkapil

Dipyrithione

Dipyrithione is reported as an ingredient of Perkapil in the following countries:

• Turkey

International Drug Name Search

Buprenorphine Hydrochloride

Class: Opiate Partial Agonists
VA Class: CN101
Chemical Name: [5α,7α(5)] - 17 - (Cyclopropylmethyl) - α - (1,1 - dimethylethyl) - 4,5 - epoxy - 18,19 - dihydro - 3 - hydroxy - 6 - methoxy - α - methyl - 6,14 - ethinomorphinan - 7 - methanol hydrochloride
Molecular Formula: C₂₉H₄₁NO₄•HCl
CAS Number: 53152-21-9
Brands: Buprenex, Suboxone, Subutex

REMS:

FDA approved a REMS for buprenorphine to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of buprenorphine and consists of the following: medication guide, elements to assure safe use, and implementation system. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Analgesic; opiate partial agonist.^{1 2 3 4 6 7 10 11 202}

Uses for Buprenorphine Hydrochloride

Pain

Relief of moderate to severe pain^{1 2 3 4 124 183 185} such as that associated with acute and chronic medical disorders including cancer,^{31 65 71 99 134 143} trigeminal neuralgia,⁴⁷ accidental trauma,⁷³ ureteral calculi,⁹⁸ and MI.^{4 71 150}

Management of postoperative pain in patients who have undergone various types of surgery, including neurologic,¹³⁸ cardiovascular (e.g., CABG, valve replacement),^{4 66 71 185} cesarean section,^{28 71 82 110} gynecologic,^{28 60 69 71 80 124 149 151 177} abdominal (e.g., cholecystectomy, bowel resection),^{28 32 44 54 64 69 71 73 76 103 145 151 184 185} urologic,^{28 124 185} general (e.g., head and neck, breast),^{53 60 151} and orthopedic (e.g., total hip replacement, spinal fusion).^{23 26 32 83 92 145 185}

Preoperative sedation and analgesia†^{35 58 60 127 140 148} and as an adjunct to surgical anesthesia†.^{24 49 58 60 62 71 121 135 142 149 192}

Opiate Dependence

Treatment of opiate dependence in an office-based outpatient setting (designated an orphan drug by FDA for this use); used alone and in fixed combination with naloxone.^{201 202}

Buprenorphine alone is preferred for the initial (i.e., induction) phase of treatment, administered under the supervision of the prescribing physician in the office setting.^{202 203} Following induction, buprenorphine in fixed combination with naloxone is preferred for maintenance treatment when use includes unsupervised administration.²⁰² Administration of buprenorphine without naloxone in an unsupervised setting should be limited to patients who cannot tolerate naloxone.²⁰²

Buprenorphine Hydrochloride Dosage and Administration

General

• Opiate Dependence


• 
  

  To avoid precipitating withdrawal, give the first dose of buprenorphine when clear, objective signs of opiate withdrawal are evident.²⁰² In individuals using heroin or other short-acting opiates, administer the first dose ≥4 hours after the last use of the opiate; however, it is preferable to initiate buprenorphine when early signs of opiate withdrawal appear.²⁰²

  
  


• 
  

  Withdrawal symptoms can occur during buprenorphine induction in patients being transferred from methadone maintenance; withdrawal symptoms appear to be more likely in those receiving higher methadone dosages (>30 mg daily) and when the first dose of buprenorphine is given shortly after the last methadone dose.²⁰²

  
  

Administration

Administer by IM or IV injection for relief of pain.^{1 2 3} Administer sublingually as a single agent or in fixed combination with naloxone for management of opiate dependence.²⁰²

Also administered by continuous IV infusion†,^{32 33 34} by IM¹⁰³ or IV^{76 79} injection using a patient-controlled infusion device†, and by epidural injection† for pain relief.^{23 24 25 26 28 29 30 31 50 78 92 192}

For drug compatibility information, see Compatibility under Stability.

Sublingual Administration

Administer as a single daily dose.²⁰²

Place tablets under the tongue and allow to dissolve; swallowing the tablets reduces bioavailability.²⁰² Drinking warm fluids prior to administration may aid dissolution.²⁰⁴

For doses requiring >2 tablets, all the tablets may be placed under the tongue at once.²⁰² Alternatively, patients may place 2 tablets under the tongue at a time if they are unable to place >2 tablets comfortably.²⁰²

To ensure consistent bioavailability, patients should adhere to the same manner of dosing with continued use.²⁰²

IV Injection

Rate of Administration

Administer over ≥2 minutes.^{1 2 3}

Continuous IV Infusion

Dilution

Dilute to a concentration of 15 mcg/mL in 0.9% sodium chloride.³²

Rate of Administration

Administer via a controlled-infusion device.³²

Epidural Injection†

Dilution

Has been diluted to a concentration of 6–30 mcg/mL in 0.9% sodium chloride.^{23 24 25 26 28 29 30 31 78 92 192}

Restricted Distribution

The Drug Addiction Treatment Act (DATA) of 2000 allows qualifying physicians to prescribe and dispense opiates in schedules III, IV, and V of the Federal Controlled Substances Act that have been approved by FDA for detoxification or maintenance treatment of opiate dependence.²⁰⁵ Prior to passage of this law, opiate dependence treatment could be provided only at specially registered clinics.²⁰³ Under DATA 2000, prescription use of buprenorphine and buprenorphine/naloxone fixed combination in the treatment of opiate dependence is limited to physicians who meet certain requirements and have notified the Secretary of the US Department of Health and Human Services of their intent to prescribe these preparations for this indication.²⁰²

Pharmacists may contact 866-287-2728 or info@buprenorphine.samhsa.gov to verify whether a physician is in compliance with the provisions of DATA.²⁰³

Dosage

Available as buprenorphine hydrochloride (injection and sublingual tablets); dosage expressed in terms of buprenorphine.^{1 2}

Also available as fixed combination of buprenorphine hydrochloride and naloxone hydrochloride (sublingual tablets); dosage generally expressed in terms of the buprenorphine content.²⁰²

Pediatric Patients

Pain

Adjust dosage according to the severity of pain, physical status of the patient, and other drugs that the patient is receiving.^{1 2}

IV or IM

Children 2–12 years of age: 2–6 mcg/kg every 4–6 hours; however, longer dosing intervals (e.g., every 6–8 hours) may be sufficient.¹ Do not use a fixed around-the-clock dosing interval until an adequate dosing interval has been established by clinical observation of the patient.¹

Children ≥13 years of age: 0.3 mg given at intervals of up to every 6 hours as necessary.^{1 2 3} Repeat initial dose (up to 0.3 mg) once in 30–60 minutes, if needed.¹

Exercise particular caution with IV administration, especially with initial doses.¹

Decrease dosage by 50% in patients who are at increased risk of respiratory depression.¹ (See Respiratory Effects under Cautions.)

Circumcision-related Pain

IM

Children 9 months to 9 years of age† undergoing circumcision: Initial dosage of 3 mcg/kg as an adjunct to surgical anesthesia, followed by additional 3-mcg/kg doses as necessary to provide analgesia postoperatively, has been used.²⁷

Adults

Pain

Adjust dosage according to the severity of pain, physical status of the patient, and other drugs that the patient is receiving.^{1 2}

IV or IM

0.3 mg given at intervals of up to every 6 hours as necessary.^{1 2 3} Repeat initial dose (up to 0.3 mg) once in 30–60 minutes, if needed.¹ A dosing interval longer than 6 hours may be adequate in some patients.^{71 72 97 99}

It may be necessary to administer single doses of up to 0.6 mg, but the manufacturer recommends that such relatively high doses only be administered IM and only to adults who are not at increased risk of respiratory depression.¹

A regimen including an initial dose of 0.3 mg followed by another 0.3-mg dose repeated in 3 hours is as effective as a single 0.6-mg dose in relieving postoperative pain.¹²⁹

Exercise particular caution with IV administration, especially with initial doses.¹

Decrease dosage by 50% in patients who are at increased risk of respiratory depression.¹ (See Respiratory Effects under Cautions.)

Continuous IV Infusion†

Dosages of 25–250 mcg/hour have been used for the management of postoperative pain.^{33 34}

Epidural Injection†

Dosages of 0.15–0.3 mg have been administered in the management of severe, chronic pain (e.g., in terminally ill patients) as frequently as every 6 hours, up to a mean total daily dosage of 0.86 mg (range: 0.15–7.2 mg).³¹

60 mcg as a single dose, up to a mean total dose of 180 mcg administered over a 48-hour period, has been used for the management of postoperative pain.²³

Supplement to Surgical Anesthesia

Epidural Injection†

Dosage of 0.3 mg has been used as a supplement to surgical anesthesia with a local anesthetic.^{24 192}

Opiate Dependence

Induction

Sublingual

Initially, buprenorphine 8 mg on day 1 and 16 mg on day 2.²⁰² From day 3 onward, administer buprenorphine in fixed combination with naloxone at the same buprenorphine dose as on day 2.²⁰²

To avoid precipitating withdrawal, give the first dose when objective and clear signs of opiate withdrawal are evident.²⁰²

Manufacturer recommends that an adequate maintenance dosage, titrated to clinical effectiveness, be achieved as rapidly as possible to prevent undue opiate withdrawal symptoms.²⁰²

Maintenance

Sublingual

Target dosage of buprenorphine in fixed combination with naloxone is 16 mg daily; however, dosages as low as 12 mg daily may be effective in some patients.²⁰² Adjust dosage in increments/decrements of 2 or 4 mg daily to a dosage that suppresses opiate withdrawal symptoms and ensures that the patient continues treatment.²⁰²

Usual dosage: 4–24 mg daily depending on the individual patient.²⁰²

Discontinuance

Sublingual

The decision to discontinue therapy after a period of maintenance or brief stabilization should be made as part of a comprehensive treatment plan.²⁰² Both gradual and abrupt discontinuance have been used; the best method for tapering dosage at the end of treatment has not been established.²⁰²

Prescribing Limits

Pediatric Patients

Pain

IV or IM

Children 2–12 years of age: Manufacturer states that there is insufficient evidence to recommend doses >6 mcg/kg or administration of a repeat dose within 30–60 minutes of the initial dose.¹

Adults

Pain

IM

There are insufficient clinical data to recommend single doses >0.6 mg for long-term use.^{1 2}

Cautions for Buprenorphine Hydrochloride

Contraindications

• 
  

  Known hypersensitivity to buprenorphine or any ingredient in the formulation;^{1 2} buprenorphine/naloxone fixed combination is contraindicated in patients with known hypersensitivity to either component.²⁰²

  
  

Warnings/Precautions

Warnings

Respiratory Effects

Possible respiratory depression,^{1 2 4 18 28 33 39 44 48 58 59 62 64 71 73 75 76 84 89 93 95 97 184 185} especially with IV administration.²⁰² Deaths have occurred when buprenorphine (usually in conjunction with a benzodiazepine) was misused via IV injection by opiate abusers.²⁰² Deaths also have occurred when used with other depressants (e.g., alcohol, other opiates).²⁰²

Administer with caution and in reduced dosages in patients with pulmonary impairment or compromised respiratory function (e.g., those with COPD, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression) or in those receiving other respiratory depressant drugs concomitantly.^{1 2 3 4 202}

Naloxone^{1 2 3 4 9 21 40 64 71 84} and doxapram^{1 2 3 9 18 21 59 70 71 76 84 185} may be only partially effective in reversing buprenorphine-induced respiratory depression; use of assisted or controlled respiration may be necessary and should be considered the principal method of management.^{1 2 3 4 20 46 83}

CNS Depression

Use with caution in comatose patients or in patients with CNS depression.¹

Performance of activities requiring mental alertness and physical coordination may be impaired.^{1 202}

Concurrent use of other CNS depressants may potentiate CNS depression.^{1 202} (See Specific Drugs under Interactions.)

Hepatic Effects

Cytolytic hepatitis and hepatitis with jaundice reported in individuals receiving buprenorphine for opiate dependence.²⁰²

Other serious adverse hepatic events (e.g., hepatic failure, hepatic necrosis, hepatorenal syndrome, hepatic encephalopathy) reported.²⁰² Some individuals had risk factors for such adverse events (i.e., preexisting hepatic enzyme abnormalities, infection with hepatitis B or C virus, concomitant use of potentially hepatotoxic drugs, ongoing illicit use of injectable drugs), but the possibility exists that buprenorphine had a causative or contributory role.²⁰²

Evaluate liver function prior to initiation of buprenorphine for the management of opiate dependence and periodically during treatment.²⁰² Evaluate carefully in the event of an adverse hepatic event.²⁰²

Withdrawal Effects

Sublingual administration of buprenorphine/naloxone fixed combination may cause withdrawal symptoms in individuals who are physically dependent on opiates if the fixed combination is administered before the agonist effects of the opiate have subsided.²⁰²

Marked and intense opiate withdrawal symptoms are likely if buprenorphine/naloxone fixed combination is misused via parenteral injection by individuals who are physically dependent on opiates.²⁰²

Buprenorphine may occasionally precipitate mild to moderate signs and symptoms of withdrawal in some patients physically dependent on opiates (because of the drug’s antagonist activity).^{1 2 87 100 112 183 202} Signs and symptoms of mild withdrawal may also appear following discontinuance of prolonged therapy with buprenorphine alone.^{4 71 84 100 112}

Head Injury and Increased Intracranial Pressure

Potential for elevation of CSF pressure as a result of vasodilation following carbon dioxide retention.¹ Opiate effects may obscure the existence, extent, or course of intracranial pathology.¹ Use with caution in patients with head injury, other intracranial lesions, or preexisting elevation in intracranial pressure.¹

Sensitivity Reactions

Hypersensitivity Reactions

Acute and chronic hypersensitivity reactions reported.²⁰² Rash,²⁰² urticaria,²⁰² and pruritus²⁰² are most common;²⁰² bronchospasm,²⁰² angioedema,²⁰² and anaphylactic shock²⁰² also have occurred.²⁰²

General Precautions

Debilitated and Special Risk Patients

Use with caution in debilitated patients and in those with hypothyroidism, Addison’s disease, toxic psychoses, prostatic hypertrophy or urethral stricture, acute alcoholism, delirium tremens, or kyphoscoliosis.^{1 202}

Biliary Disease

Use with caution in patients with dysfunction of the biliary tract^{1 2 202} or those undergoing biliary tract surgery,⁵⁴ since the drug may increase pressure within the common bile duct.^{1 2 21 40 52 54 202}

Acute Abdominal Conditions

May obscure the diagnosis and/or clinical course of patients with acute abdominal conditions.²⁰²

Cardiovascular Effects

Possible orthostatic hypotension in patients who are ambulatory.²⁰²

Dependence

Possible psychologic dependence to buprenorphine’s opiate agonist activity.^{1 12 112} Limited physical dependence may occur^{41 85 86 107 108 109 111 112 147} infrequently;^{1 2 4 74 178} tolerance to the drug’s opiate agonist activity develops rarely,^{107 109 171 178} if at all.^{84 96 123}

Fixed-combination Preparation

When buprenorphine is used in fixed combination with naloxone, consider the cautions, precautions, and contraindications associated with naloxone.²⁰²

Specific Populations

Pregnancy

Category C.^{1 202}

Safety and efficacy during labor and delivery not established.^{1 2}

Lactation

Distributed into milk.^{1 202} Women should not breast-feed infants while receiving buprenorphine.^{1 202}

Pediatric Use

Safety and efficacy of parenteral buprenorphine as an analgesic not established in children <2 years of age.^{1 2} Has been used parenterally as a supplement to surgical anesthesia†²⁷ and as an analgesic in the management of postoperative pain^{1 27} and severe chronic pain (e.g., in terminally ill patients)⁹⁴ in a limited number of children 9 months to 18 years of age.^{1 27 94}

Safety and efficacy of buprenorphine and buprenorphine/naloxone fixed combination not established for the management of opiate dependence in children <16 years of age.²⁰²

Geriatric Use

Use with caution.^{1 202}

Hepatic Impairment

Metabolized in the liver; therefore, activity of the drug may be increased and/or prolonged in patients with hepatic impairment.^{1 2} Use with caution in patients with severe hepatic impairment.^{1 2 202}

When used for the treatment of opiate dependence in patients with hepatic impairment, adjust dosage and observe the patient for potential withdrawal symptoms.²⁰²

Renal Impairment

Use with caution in patients with severe renal impairment.^{1 2 202}

Common Adverse Effects

Sedation (e.g., drowsiness),^{1 2 3 9 40 44 48 51 53 65 67 69 71 72 75 79 83 95 96 98 110 183 184 185} dizziness,^{1 2 3 4 9 44 71 99 183 185} vertigo,^{1 2 3} nausea.^{1 2 3 4 40 44 49 51 53 67 71 76 79 83 93 105 183 184 185 192}

Interactions for Buprenorphine Hydrochloride

Metabolized principally by CYP3A4.^{1 202}

Drugs Affecting Microsomal Enzymes

CYP3A4 inhibitors: Potential pharmacokinetic interaction (increased plasma buprenorphine concentrations).^{1 202} Closely monitor buprenorphine or buprenorphine/naloxone dosage; adjust dosage if necessary.^{1 202}

CYP3A4 inducers: Potential pharmacokinetic interaction (decreased plasma buprenorphine concentrations).^{1 202} Closely monitor patient.^{1 202}

Drugs Affecting Hepatic Blood Flow

Drugs that reduce hepatic blood flow may decrease the rate of hepatic elimination of buprenorphine.^{1 2 4 116}

Specific Drugs

Drug	Interaction	Comments
Anesthetics, local (e.g., bupivacaine, mepivacaine)	Possible potentiation of anesthetic effect24 92 and more rapid onset and prolonged duration of analgesia24
Anticoagulants, (phenprocoumon, no longer commercially available)	Possible purpuric response1 2
Anticonvulsants (carbamazepine, phenobarbital, phenytoin)	Possible decrease in plasma buprenorphine concentrations1 202	Monitor closely; adjust dosage of buprenorphine or buprenorphine/naloxone, if necessary1 202
Antifungals, azoles (e.g., ketoconazole)	Increased plasma buprenorphine concentrations1 202	Monitor closely; adjust dosage of buprenorphine or buprenorphine/naloxone, if necessary1 202
Benzodiazepines (e.g., diazepam, lorazepam)	Reports of death or coma when buprenorphine was misused (e.g., self-injection of crushed tablets) via IV injection with benzodiazepines by drug abusers202 Respiratory and cardiovascular collapse reported in several patients receiving usual doses of IV buprenorphine and oral diazepam concomitantly1 2 59 Bradycardia, respiratory depression, and prolonged drowsiness reported following IV buprenorphine administration during surgery in a patient who had received oral lorazepam preoperatively36	Use buprenorphine or buprenorphine/naloxone with caution in patients receiving benzodiazepines or other drugs with CNS effects202
CNS depressants (e.g., opiate agonists, tranquilizers, general anesthetics, sedatives/hypnotics, alcohol)	Possible potentiation of CNS depression1 2 3 35 37 42 59 60 64	Use with caution; reduce dosage of at least one of the drugs1 2 3 202
Droperidol	Concomitant administration has produced satisfactory analgesia (during and after surgery60 and also in a terminally ill patient with severe, chronic pain that was previously unresponsive to buprenorphine alone37 )
Fentanyl	Concomitant administration produced satisfactory analgesia of prolonged duration with minimal respiratory depression; patient was aroused quickly and easily following surgery70
Halothane	Potential for increased and/or prolonged activity of buprenorphine secondary to reduced hepatic elimination of the drug1 2 4 116 186 191	Use with caution; reduce dosage of at least one of the drugs1 186 189
HIV protease inhibitors (indinavir, ritonavir, saquinavir)	Increased plasma buprenorphine concentrations1 202	Monitor closely; adjust dosage of buprenorphine or buprenorphine/naloxone, if necessary1 202
Macrolide antibiotics (e.g., erythromycin)	Increased plasma buprenorphine concentrations1 202	Monitor closely; adjust dosage of buprenorphine or buprenorphine/naloxone, if necessary1 202
MAO inhibitors	Possible additive effect or potentiation of CNS depression1 2 3	Use with caution1 2 3
Naloxone	In patients who received a single, high dose of buprenorphine before undergoing cholecystectomy with balanced anesthesia and experienced pain in the immediate postoperative phase, addition of naloxone resulted in adequate analgesia, possibly by counteracting dominant antagonistic effects of buprenorphine58 148
Rifampin	Possible decrease in plasma buprenorphine concentrations1 202	Monitor closely; adjust dosage of buprenorphine or buprenorphine/naloxone, if necessary1 202

Buprenorphine Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Rapidly and approximately 40–90% absorbed following IM administration.^{116 118} Approximately 55% (range: 15–95%) absorbed following sublingual administration.^{118 119} Following oral administration, buprenorphine undergoes extensive first-pass metabolism in the GI mucosa and liver.^{122 131}

Following IV administration of a single dose, mean peak plasma drug concentrations^{4 116} occurred within 2 minutes.^{4 116 118} Following IM administration of a second dose 3 hours after the initial IV dose, mean peak plasma concentrations occurred within 2–5 minutes.^{4 9 116 118}

Approximately 10 minutes after administration, plasma buprenorphine concentrations are similar following IV or IM injection.^{4 9 116 118}

Onset

Following parenteral administration of single doses in postoperative patients,^{1 2 3 9 16 21 42 48 71 72 80 82 96 97 98 121 123 124 127 128} the onset of analgesia usually occurs within 10–30 minutes.^{1 2 3 9 16 17 96 123 124 128 185} Peak analgesia usually occurs within 60 minutes^{1 71 80 96 128 185} but may occur within 15 minutes in some patients.⁷¹

Duration

Analgesia generally persists for 6 hours following single IM or IV doses,^{1 2 3 16 21 71 72 82 96 121 124 185} but has persisted for 4–10 hours following single IM doses^{1 2 3 16 21 71 72 82 96 97 98 123 124 127 184} and 2–24 hours following single IV doses.^{42 48 71 80 121 152}

Distribution

Extent

Rapidly (within several minutes) distributes into CSF following IV administration;^{3 63 117 120} CSF concentrations appear to be approximately 15–25% of concurrent plasma concentrations.¹¹⁷

Crosses the placenta in rats;⁷¹ not known whether buprenorphine crosses the placenta in humans.³

Distributes into human milk.^{1 2 3 4}

Plasma Protein Binding

Approximately 96%^{4 15 71} (mainly α- and β-globulins;^{4 71} does not appear to bind substantially to albumin).⁴

Elimination

Metabolism

Almost completely metabolized in the liver,^{1 2 3 21 116} principally by N-dealkylation (mediated by CYP3A4)²⁰² to form norbuprenorphine.^{3 4 71 113 114 115 118 122 125 202} Buprenorphine and norbuprenorphine undergo conjugation with glucuronic acid.^{3 71 118 122 125}

Elimination Route

Eliminated principally in feces^{3 4 113} (via biliary excretion^{4 113} ) and also in urine^{114 122 170} as unchanged drug and metabolites.

Half-life

Biphasic or triphasic;^{114 116 118} half-life of terminal elimination phase is approximately 2.2 hours (range: 1.2–7.2 hours) following IV administration,^{1 2 4 21 40 118 119} and mean elimination half-life from plasma is 37 hours following sublingual administration.²⁰²

Stability

Storage

Sublingual

Tablets

25°C (may be exposed to 15–30°C).²⁰²

Parenteral

Injection

<40°C; protect from prolonged exposure to light.¹

Compatibility

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

Parenteral

Drug Compatibility

Admixture CompatibilityHID

Compatible
Bupivacaine HCl
Glycopyrrolate with haloperidol lactate
Incompatible

Fludecate

Fludecate may be available in the countries listed below.

Ingredient matches for Fludecate

Fluphenazine

Fluphenazine decanoate (a derivative of Fluphenazine) is reported as an ingredient of Fludecate in the following countries:

• Israel

International Drug Name Search