Pavabid Plateau

Generic Name: papaverine (pa PAV uh reen)

Brand Names: Papacon, Para-Time S. R., Pavabid Plateau, Pavacot, Pavagen

What is Pavabid Plateau (papaverine)?

Papaverine is in a class of drugs called vasodilators. Papaverine relaxes veins and arteries, which makes them wider and allows blood to pass through them more easily. These actions may help to increase the amount of oxygen-rich blood in your brain, heart, and muscles.

Papaverine may also be useful in treating conditions involving spasms of the intestines and urinary tract.

Papaverine may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about Pavabid Plateau (papaverine)?

Use caution when driving, operating machinery, or performing other hazardous activities. Papaverine may cause dizziness. If you experience dizziness, avoid these activities. If you experience dizziness, rise slowly from a sitting or lying position to avoid falling. Use alcohol cautiously. Alcohol may increase drowsiness and dizziness while you are taking papaverine.

Notify your doctor if you experience especially bothersome sweating, rash, flushing, headache, tiredness, yellowing of your skin, nausea, decreased appetite, diarrhea, or constipation.

Who should not take Pavabid Plateau (papaverine)?

Before taking this medication, tell your doctor if you have

• 
  

  heart disease or irregular heartbeats,

  
  


• 
  

  liver disease,

  
  


• 
  

  glaucoma, or

  
  


• 
  

  Parkinson's disease.

  
  

You may not be able to take papaverine, or you may require a lower dose or special monitoring during treatment if you have any of the conditions listed above.

Papaverine is in the FDA pregnancy category C. This means that it is not known whether papaverine will harm an unborn baby. Do not take papaverine without first talking to your doctor if you are pregnant. It is not known whether papaverine passes into breast milk. Do not take this medication without first talking to your doctor if you are breast-feeding a baby.

How should I take Pavabid Plateau (papaverine)?

Take papaverine exactly as directed by your doctor. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain them to you.

Take each dose with a full glass of water.

The regular-release form of papaverine is usually taken three to five times a day. The timed-release tablets and capsules are usually taken two or three times a day (every 8 to 12 hours). Follow your doctor's instructions.

Do not crush, chew, break, or open the timed-release tablets or capsules. Swallow them whole. They are specially formulated to release slowly in your body. Store papaverine at room temperature away from moisture and heat.

What happens if I miss a dose?

Take the missed dose as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and take only your next regularly scheduled dose. Do not take a double dose of this medication.

What happens if I overdose?

Seek emergency medical attention.

Symptoms of a papaverine overdose include drowsiness, weakness, double vision, poor coordination, headache, blue-colored lips or skin, and coma.

What should I avoid while taking Pavabid Plateau (papaverine)?

Use caution when driving, operating machinery, or performing other hazardous activities. Papaverine may cause dizziness. If you experience dizziness, avoid these activities. If you experience dizziness, rise slowly from a sitting or lying position to avoid falling. Use alcohol cautiously. Alcohol may increase drowsiness and dizziness while you are taking papaverine. Do not crush, chew, break, or open the timed-release tablets or capsules. Swallow them whole. These are specially formulated to release slowly in your body.

Pavabid Plateau (papaverine) side effects

Stop taking papaverine and seek emergency medical attention if you experience an allergic reaction (difficulty breathing; closing of your throat; swelling of your lips, tongue, or face; or hives).

Stop taking papaverine and contact your doctor if your skin or eyes develop a yellow tint.

Other, less serious side effects may be more likely to occur. Continue to take papaverine and talk to your doctor if you experience

• 
  

  nausea, decreased appetite, diarrhea, or constipation;

  
  


• 
  

  dizziness or drowsiness;

  
  


• 
  

  headache;

  
  


• 
  

  sweating and flushing;

  
  


• 
  

  a rash; or

  
  


• 
  

  irregular heartbeats.

  
  

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Pavabid Plateau (papaverine)?

Papaverine may decrease the effects of levodopa (Dopar, Larodopa) which is used to treat Parkinson's disease. You may need a change in your levodopa dosage if you are taking levodopa.

Drugs other than those listed here may also interact with papaverine or affect your condition. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines.

More Pavabid Plateau resources

• Pavabid Plateau Use in Pregnancy & Breastfeeding
• Drug Images
• Pavabid Plateau Drug Interactions
• Pavabid Plateau Support Group
• 0 Reviews · Be the first to review/rate this drug

• Papaverine MedFacts Consumer Leaflet (Wolters Kluwer)


• Papacon Advanced Consumer (Micromedex) - Includes Dosage Information


• Papaverine Hydrochloride Monograph (AHFS DI)

Where can I get more information?

• Your pharmacist has additional information about papaverine written for health professionals that you may read.

CIS-MDP

Dosage Form: injection

DIAGNOSTIC FOR INTRAVENOUS USE

Rx Only

Description

CIS-MDP™  Kit for the Preparation of Technetium Tc 99m Medronate is a multidose reaction vial which contains the sterile, non-pyrogenic, non-radioactive ingredients necessary to produce Technetium Tc 99m Medronate Injection for diagnostic use by Intravenous injection.

Each 10mL multidose vial contains:

Medronic acid: 20 mg

Ascorbic acid: 1 mg

Stannous fluoride, SnF2: 0.13 mg (minimum)

Total tin (maximum, as stannous fluoride, SnF2): 0.38 mg

The pH is adjusted to 6.5 (6.3 to 6.7) with sodium hydroxide and/or hydrochloric acid prior to lyophilization. No bacteriostatic preservative is present in the vial. The contents of the vial are lyophilized and sealed under nitrogen at the time of manufacture. The structural formula is:

When a solution of sterile, non-pyrogenic, oxidant-free Sodium Pertechnetate Tc 99m Injection is added to the vial, the diagnostic agent, Technetium Tc 99m Medronate is formed for administration by intravenous injection. The pH of the reconstituted product is 5.4 to 6.8. The precise structure of Technetium Tc 99m Medronate Injection is not known at this time.

PHYSICAL CHARACTERISTICS:

Technetium Tc 99m decays by isomeric transition with a physical half-life of 6.02 hours1. The principal photon that is useful for detection and imaging studies is listed in Table 1.

TABLE 1 Principal Radiation Emission Data

Radiation	Mean % per Disintegration	Mean Energy (keV)
Gamma-2	89.07	140.5

1

Kocher, DC: Radioactive Decay Data Tables, DOE/TIC-11026, 108, 1981.

EXTERNAL RADIATION:

The specific gamma ray constant for Tc 99m is 0.78 R/millicurie-hr at 1 cm. The first half-value layer is 0.017 cm of lead (Pb). A range of values for the relative attenuation of the radiation emitted by this radionuclide that results from interposition of the various thicknesses of Pb is shown in Table 2. To facilitate control of the radiation exposure from millicurie amounts of this radionuclide, the use of a 0.25 cm thickness of Pb will attenuate the radiation emitted by a factor of about 1,000.

TABLE 2 Radiation Attenuation by Lead Shielding

Shield Thickness (Pb) cm	Coefficient of Attenuation
0.017	0.5
0.08	10-1
0.16	10-2
0.25	10-3
0.33	10-4

 To correct for physical decay of this radionuclide, the fractions that remain at selected intervals after the time of calibration are shown in Table 3.

TABLE 3 Physical Decay Chart: Tc 99m, Half-Life 6.02 Hours

* Calibration Time
Hours	Fraction Remaining	Hours	Fraction Remaining
0*	1.000	7	0.447
1	0.891	8	0.398
2	0.794	9	0.355
3	0.708	10	0.316
4	0.631	11	0.282
5	0.562	12	0.251
6	0.501

Clinical Pharmacology

During the initial 24 hours following intravenous injection of Technetium Tc 99m Medronate, about 50% of each dose is retained in the skeleton, and about 50% is excreted in the urine. Upon intravenous injection, Technetium Tc 99m Medronate exhibits a specific affinity for areas of altered osteogenesis. In humans, blood levels fall to 4 to 10% of the injected dose by two hours post-injection and to 3 to 5% by three hours.

Uptake of Technetium Tc 99m Medronate Injection in bone appears to be related to osteogenic activity and to skeletal blood perfusion. The deposition in the skeleton is bilaterally symmetrical, with increased accumulation in the axial structure as compared to the appendicular skeleton. There is increased activity in the distal aspect on long bones as compared to the diaphyses.

Indications and Usage

Technetium Tc 99m Medronate Injection may be used as a bone imaging agent to delineate areas of altered osteogenesis.

Contraindications

None known.

Warnings

This class of compounds is known to complex cations such as calcium. Particular caution should be used with patients who have, or may be predisposed to hypocalcemia (i.e., alkalosis).

Preliminary reports indicate impairment of brain scans using Sodium Pertechnetate Tc 99m Injection which have been preceded by a bone scan using an agent containing stannous ions. The impairment may result in false-positive or false-negative brain scans. It is recommended, where feasible, that brain scans precede bone imaging procedures. Alternatively, a brain imaging agent such as Technetium Tc 99m Pentetate Injection may be employed.

Precautions

General

Contents of the vial are intended only for use in the preparation of Technetium Tc 99m Medronate Injection and are NOT to be administered directly to the patient.

Technetium Tc 99m Medronate Injection as well as other radioactive drugs must be handled with care, and appropriate safety measures should be used to minimize radiation exposure to the patient and clinical personnel consistent with proper patient management.

To minimize radiation dose to the bladder, the patients should be encouraged to drink fluids and to void immediately before the examination and as often thereafter as possible for the next 4 to 6 hours.

Technetium Tc 99m Medronate Injection should be formulated within six (6) hours prior to clinical use. Optimal imaging results are obtained 1 to 4 hours after administration.

The finding of an abnormal concentration of radioactivity implies the existence of underlying pathology, but further study is required to distinguish benign from malignant lesions.

The image quality may be adversely affected by obesity, old age, or impaired renal function.

The components of the kit are sterile and non-pyrogenic. It is essential to follow directions carefully and to adhere to strict aseptic procedures during preparation. Technetium Tc 99m labeling reactions involved depend on maintaining the stannous ion in the reduced state. Hence, Sodium Pertechnetate Tc 99m Injection containing oxidants should not be used.

The preparation contains no bacteriostatic preservative. Technetium Tc 99m Medronate Injection should be stored at 20-25ºC (68-77ºF) and discarded 6 hours after reconstitution. The solution should not be used if the contents are cloudy.

Vials are sealed under nitrogen: air or oxygen is harmful to the contents of the vials and the vials should not be vented.

The components of the CIS-MDP are supplied sterile and non-pyrogenic. Aseptic procedures normally employed in making additions and withdrawals for sterile, non-pyrogenic containers should be used during addition of the pertechnetate solution and the withdrawal of doses for patient administration.

Shielding should be utilized when preparing Technetium Tc 99m Medronate Injection.

No special handling is required for the non-radioactive drug product.

Radiopharmaceuticals should be used only by physicians who are qualified by training and experience in the safe use and handling of radionuclides, and whose experience and training have been approved by the appropriate government agency authorized to license the use of radionuclides.

Carcinogenesis, mutagenesis, impairment of fertility

No long-term animal studies have been performed to evaluate carcinogenic potential or whether Technetium Tc 99m Medronate Injection affects fertility in males or females. Mutagenesis studies have not been conducted.

Pregnancy

Category C

Animal reproduction and teratogenicity studies have not been conducted on Technetium Tc 99m Medronate Injection. It is also not known whether Technetium Tc 99m Medronate Injection can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Technetium Tc 99m Medronate Injection should be given to a pregnant woman only if clearly needed.

Ideally, examinations using radiopharmaceuticals, especially those elective in nature, on a woman of childbearing capability, should be performed during the first few (approximately 10) days following the onset of menses.

Nursing mothers

Technetium Tc 99m Medronate Injection is excreted in human milk during lactation; therefore, formula feeding should be substituted for breast feeding.

Pediatric Use

Safety and effectiveness in pediatric subjects have not been established.

Adverse Reactions

Several adverse reactions due to Technetium Tc 99m Medronate Injection have been reported. These were usually hypersensitivity reactions characterized by itching, various skin rashes, hypotension, chills, nausea and vomiting. There have also been rare cases of dizziness and asthenia associated with the use of Technetium Tc 99m Medronate.

Dosage and Administration

Shielding should be utilized when preparing Technetium Tc 99m Medronate Injection.

After preparation with oxidant-free Sodium Pertechnetate Tc 99m Injection, the suggested dose range of Technetium Tc 99m Medronate Injection in the average ADULT patient (70 kg.) is:

370-740 megabecquerels: (10-20 millicuries) given intravenously.

Imaging is optimal at 1 to 4 hours post Injection.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

The patient dose should be measured by a suitable radioactivity calibration system immediately prior to administration.

Radiation Dosimetry

The effective half-life was assumed to be the physical half-life for all calculated values. The estimated radiation absorbed doses to an average ADULT patient (70 kg) from an intravenous injection of a maximum of 740 megabecquerels (20 millicuries) of Technetium Tc 99m Medronate Injection are shown in Table 4.

TABLE4 Estimated Absorbed Radiation Dose* Technetium Tc 99m Medronate

* Method of calculation: “S” Absorbed Dose Per Unit Cumulated Activity for Selected Radionuclides and Organs, MIRD Pamphlet No 11 (1975)
Organ		(MGy/740 MBq)	(Rads / 20 mCi)
Total Body		1.3	0.13
Bone Total		7.0	0.70
Red Marrow		5.6	0.56
Kidneys		8.0	0.80
Liver		0.6	0.06
Bladder Wall	2 hour void	26	2.60
	4.8 hour void	62	6.20
Ovaries	2 hour void	2.4	0.24
	4.8 hour void	3.4	0.34
Testes	2 hour void	1.6	0.16
	4.8 hour void	2.2	0.22

How is CIS-MDP Supplied

 The CIS-MDP Kit for the Preparation of Technetium Tc 99m Medronate Injection is supplied in kits of five (5) or thirty (30) sterile, non-pyrogenic vials. Each 10 mL multidose vial contains 20 mg medronic acid, 1 mg ascorbic acid, 0.13 mg minimum stannous fluoride (SnF2) and 0.38 mg maximum total tin, as stannous fluoride, SnF2 in lyophilized form. The pH is adjusted with sodium hydroxide and/or hydrochloric acid prior to lyophilization. The vial does not contain a preservative. The contents of the vial are lyophilized and sealed under nitrogen at the time of manufacture. The pH of the reconstituted product is 5.4 to 6.8.

Kit Contents

Included in each five (5) vial kit is one (1) package insert and ten (10) radiation labels. Included in each thirty (30) vial kit is one (1) package insert and sixty (60) radiation labels.

Storage

Store the product as supplied at 20-25°C (68-77°F) [See USP]. After reconstitution store at 20-25°C (68-77°F) [See USP] (see DOSAGE AND ADMINISTRATION).

DIRECTIONS FOR PREPARATION OF TECHNETIUM Tc 99m MEDRONATE INJECTION:

Procedural Precautions

The lyophilized powder in the reaction vial is sterile and non-pyrogenic and does not contain a preservative. Shielded syringes and aseptic procedures normally employed in making additions and withdrawals from sterile, non-pyrogenic containers should be used during addition of pertechnetate solution to the reaction vial and the withdrawal of doses for patient administration.

If sodium pertechnetate Tc 99m must be diluted prior to injection into the reaction vial, only Sodium Chloride Injection USP 0.9% (without preservatives) should be used.

Technetium Tc 99m Medronate Injection is prepared from CIS-MDP  by the following aseptic procedure:

1. Waterproof gloves should be worn during the preparation procedure. Remove the plastic disk from the vial and swab the top of the vial closure with alcohol to sanitize the surface.


2. Complete the radiation label and affix to the vial. Place the reaction vial in a suitable radiation shield.


3. With a sterile, shielded syringe aseptically obtain 0.5-5 mL, of a suitable, oxidant-free, sterile, non-pyrogenic Sodium Pertechnetate Tc 99m Injection containing no more than 18.5 gigabecquerels (500 millicuries). Aseptically add the Sodium Pertechnetate Tc 99m Injection to the vial. Be sure to maintain a nitrogen atmosphere in the vial by not introducing air during reconstitution.


4. Swirl the contents of the vial for one minute, and let stand for at least 10 minutes.


5. Record time and date of preparation.


6. The radiochemical purity of the prepared radiopharmaceutical should be checked prior to patient administration.


7. Examine vial contents for particulates and discoloration prior to injection. Do not use if solution is cloudy.


8. Withdrawals for administration must be made aseptically using a sterile shielded syringe and needle. Since the vials contain nitrogen to prevent oxidation of the complex, the vials should not be vented. If repeated withdrawals are made from a vial, the replacement of contents with air should be minimized.


9. Use within six (6) hours of preparation. For optimum results, this time should be minimized. The vial contains no bacteriostatic preservative. After reconstitution store at 20-25°C (68-77°F)[See USP].


10. The patient dose should be measured by a suitable radioactivity calibration system immediately prior to administration.

NDC# 045567-0040-1 (5 vial pack)

NDC# 045567-0040-2 (30 vial pack)

This reagent kit for the preparation of a radiopharmaceutical is approved for use by persons licensed pursuant to Section 120.533, Code of Massachusetts Regulation 105, or under equivalent license of the U.S. Nuclear Regulatory Commission or an Agreement State.

RM 2M-027

04/05

CIS-US, Inc.

10 DeAngelo Drive

Bedford, MA 01730

718-275-7129

CIS-MDP  medronate disodium  injection, powder, lyophilized, for solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 45567-0040 Route of Administration INTRAVENOUS DEA Schedule

INGREDIENTS Name (Active Moiety) Type Strength medronate disodium (medronic acid) Active 20 MILLIGRAM  In 1 VIAL ascorbic acid Inactive 1 MILLIGRAM  In 1  stannous flouride Inactive 0.13 MILLIGRAM  In 1 VIAL

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 45567-0040-1 5 VIAL In 1 KIT contains a VIAL, GLASS 1 1 VIAL In 1 VIAL, GLASS This package is contained within the KIT (45567-0040-1) 2 45567-0040-2 30 VIAL In 1 KIT contains a VIAL, GLASS 2 1 VIAL In 1 VIAL, GLASS This package is contained within the KIT (45567-0040-2)

Revised: 10/2006CIS-US, Inc.

More CIS-MDP resources

• CIS-MDP Support Group
• 0 Reviews · Be the first to review/rate this drug

Citrate Salts, Citric Acid, Citric Acid Monohydrate, Potassium Citrate, Potassium Citrate Monohydrate, Sodium Citrate, Sodium Citrate and Citric Acid, Sodium Citrate Dihydrate

Class: Alkalinizing Agents
VA Class: TN400
CAS Number: 77-92-9
Brands: Bicitra, Cytra-2, Cytra-3, Cytra-K, Oracit

Introduction

Alkalinizing agents.^{104 105 106 107 108 109 a}

Uses for Citrate Salts, Citric Acid, Citric Acid Monohydrate, Potassium Citrate, Potassium Citrate Monohydrate, Sodium Citrate, Sodium Citrate and Citric Acid, Sodium Citrate Dihydrate

Preparations containing sodium citrate and citric acid are especially useful when administration of potassium salts is undesirable or contraindicated,^{105 109} while those containing potassium citrate and citric acid are used when administration of sodium salts is undesirable or contraindicated.^{107 108 111}

Alkalinization of Urine

Citrates are used for alkalinization of urine (as alternatives to sodium bicarbonate) in conditions where long-term maintenance of an alkaline urine is desirable (e.g., management of uric acid and cystine calculi of the urinary tract).^{104 106 107 108 109 111 112 a}

Chronic Metabolic Acidosis

Citrates are used for management of chronic metabolic acidosis associated with conditions such as chronic renal insufficiency or renal tubular acidosis.^{104 105 106 107 108 109 111 114 a}

Adjuvant in Gout Therapy

Citrates are used as adjuvants to uricosuric agents in gout therapy.^{108 111 112}

Prevention of Milk Curdling

Sodium citrate has been used to alter cow’s milk so that large hard curds are not formed in the stomach of feeding infants†.^a

Gastric Acid Neutralization

Some citrate salts (e.g., sodium citrate and citric acid) also used for buffering and neutralizing gastric hydrochloric acid.^{105 109}

Compounding Uses

Sodium citrate and citric acid may be used as a buffer to maintain an approximate pH in various extemporaneous formulations.^a (See Compatibility under Stability.)

Citrate Salts, Citric Acid, Citric Acid Monohydrate, Potassium Citrate, Potassium Citrate Monohydrate, Sodium Citrate, Sodium Citrate and Citric Acid, Sodium Citrate Dihydrate Dosage and Administration

General

• 
  

  Selection of a specific preparation may in part be determined by potassium and sodium content.^a

  
  


• 
  

  Unlike sodium bicarbonate solution, citrate solutions generally are considered highly palatable and pleasant tasting, and may be particularly useful as alkalinizing agents in patients who do not tolerate the taste of sodium bicarbonate oral solution.^{105 106 107 108 109 111 112 a}

  
  

Administration

Oral Administration

Dilute oral citrate solutions with adequate amounts of water prior to administration to minimize the risk of GI complications, and follow with additional water after administration;^{104 105 106 108 109 111 112 a} enhance palatability by chilling the solution before administration.^{109 a}

Reconstitute contents of single-dose packets containing potassium citrate and citric acid for oral solution with cool water or juice prior to administration; give additional water or juice after administration.^{100 108}

Administer oral citrate solutions after meals to avoid the saline laxative effect of the drugs as well as upset stomach.^{105 106 107 108 109 111 112 a}

Shake oral solutions well before use, unless otherwise directed.^{105 106 107}

Reconstitution

Reconstitute contents of single-dose packets containing potassium citrate and citric acid for oral solution with at least 180 mL of cool water or juice prior to administration.^{100 108}

Dosage

Pediatric Patients

General Pediatric Dosage

Potassium Citrate and Citric Acid

Oral

Usually, 5–15 mL of solution, diluted with 1/2 glass of water, after meals and at bedtime.^{107 111}

Do not use single-dose packets of potassium citrate and citric acid for oral solution in pediatric patients, since dosage for these patients can be more easily regulated with the commercially available oral solution.¹⁰⁸ Individualize dosage according to the patient’s tolerance and response.^a

Sodium Citrate and Citric Acid

Oral

Children ≥2 years of age: Usually, 5–15 mL of solution, diluted in 30–90 mL of water, after meals and at bedtime;^{105 109} individualize dosage according to patient’s tolerance and response.^a Consult a clinician for use in children <2 years of age.^{105 109}

Tricitrates

Oral

Usually, 5–15 mL 4 times daily, after meals and at bedtime;^{106 112} individualize dosage according to patient’s tolerance and response.^a

Prevention of Milk Curdling

Sodium Citrate

Oral

Prevention of the formation of large curds in the stomach of feeding infants: Add 100 mg of sodium citrate to each 30 mL of cow’s milk.^a

Adults

General Adult Dosage

Potassium Citrate and Citric Acid

Oral

Usually, 15–30 mL of solution, diluted with 1 glass of water, after meals and at bedtime.^{107 111} The usual dosage of potassium citrate and citric acid for oral solution is one single-dose packet (containing 3300 mg of potassium citrate monohydrate and 1002 mg of citric acid monohydrate), reconstituted as directed 4 times daily, after meals and at bedtime.¹⁰⁸ Individualize dosage according to patient’s tolerance and response.^a

Sodium Citrate

Oral

Usually, 1–2 g every 2–4 hours as necessary for alkalinization effect.^a

Sodium Citrate and Citric Acid

Oral

Usually, 10–30 mL of solution,¹⁰⁴ diluted in 30–90 mL of water, after meals and at bedtime.^{104 105} Individualize dosage according to patient’s tolerance and response.^a

Tricitrates

Oral

Usually, 15–30 mL of solution diluted in water 4 times daily, after meals and at bedtime.^{106 112} Individualize dosage according to the patient’s tolerance and response.^a

Gastric Acid Neutralization

Sodium Citrate and Citric Acid

Oral

15 mL of solution, diluted in 15 mL of water, taken as a single dose.¹⁰⁵

Cautions for Citrate Salts, Citric Acid, Citric Acid Monohydrate, Potassium Citrate, Potassium Citrate Monohydrate, Sodium Citrate, Sodium Citrate and Citric Acid, Sodium Citrate Dihydrate

Contraindications

• 
  

  Potassium citrate and citric acid (oral solution and for oral solution [Cytra-K Crystals]): Manufacturer states that preparation is contraindicated in severe renal impairment with oliguria or azotemia, untreated Addison’s disease, adynamia episodica hereditaria, acute dehydration, heat cramps, anuria, severe myocardial damage, or hyperkalemia (from any cause).^{108 111}

  
  


• 
  

  Sodium citrate and citric acid oral solution (Bicitra, Cytra-2): Manufacturers state that preparations are contraindicated in patients requiring sodium-restricted diet and those with severe renal impairment.^{105 109}

  
  


• 
  

  Sodium citrate and citric acid (Oracit): Manufacturer states that preparation is contraindicated in severe renal impairment, oliguria or azotemia, untreated Addison’s disease, adynamia episodica hereditaria, acute dehydration, heat cramp, anuria, severe myocardial damage, and hyperkalemia.¹⁰⁴

  
  


• 
  

  Tricitrates oral solution (e.g., Cytra-3): Manufacturer states that preparation is contraindicated in severe renal impairment with oliguria and azotemia, untreated Addison’s disease, and severe myocardial damage.^{112 a}

  
  

Warnings/Precautions

Warnings

Electrolyte and Acid-Base Disturbances

Potassium-containing formulations: Large doses may cause hyperkalemia and alkalosis, especially in patients with renal impairment.^{108 111} Listlessness, weakness, mental confusion, and tingling of the extremities may be associated with hyperkalemia.^{108 111 112}

Sodium-containing formulations: Excessive doses may cause metabolic alkalosis, especially in patients with hypocalcemia or renal impairment.^{105 109 a} Possible tetany or depression of the heart associated with decreased ionized calcium concentrations may occur with large doses.^a

General Precautions

Concomitant Disease

Sodium-containing formulations: Use with extreme caution in patients with low urine output (unless patient is closely supervised), CHF, hypertension, renal dysfunction, peripheral or pulmonary edema, or toxemia of pregnancy.^{105 109 112}

Potassium-containing formulations: Use with extreme caution in patients in whom excessive potassium may cause deleterious effects.^a

Adequate Patient Evaluation and Monitoring

Evaluate patient’s clinical condition and monitor serum electrolyte concentrations and acid-base balance periodically, especially in patients with renal impairment, to avoid complications.^{104 105 108 109 a}

Laxative Effects

Possible saline laxative effects; dilute citrate solution with water and administer after meals to minimize this effect.^{104 105 108 a}

Specific Populations

Pregnancy

Potassium citrate: Category A.¹¹⁰

Lactation

Not known whether potassium citrate is distributed into milk.¹¹⁰ Because potassium freely distributes into and out of milk, use of potassium citrate by nursing woman with normal plasma potassium concentrations should have no adverse effect on nursing infant; milk potassium concentrations may be increased in hyperkalemic women.¹¹⁰

Renal Impairment

Use citrates with caution in patients with renal impairment.^{105 109 112} Monitor serum electrolyte concentrations and acid-base balance to avoid complications (see Warnings/Precautions under Cautions).^{104 105 108 109 111 112 a} Manufacturers state that citrates are contraindicated in patients with severe renal impairment (see Contraindications under Cautions).^{104 105 108 109 111 112 a}

Common Adverse Effects

Generally well tolerated at recommended dosages in patients with normal renal function and urine output.^{104 105 108 109 a} (See Warnings under Cautions.)

Interactions for Citrate Salts, Citric Acid, Citric Acid Monohydrate, Potassium Citrate, Potassium Citrate Monohydrate, Sodium Citrate, Sodium Citrate and Citric Acid, Sodium Citrate Dihydrate

Specific Drugs

Drug	Interaction	Comments
ACE inhibitors	Potential for hyperkalemia and toxicity with citrate preparations containing potassium108 111 112 116
Amphetamines	Urinary alkalinization may decrease renal elimination of amphetamines116	Avoid concomitant use, especially in amphetamine overdosage116
Antacids (aluminum-containing)	Increased GI absorption of aluminum;113 114 115 risk of aluminum toxicity in patients with chronic kidney disease receiving citrates and aluminum-containing drugs114	Avoid concomitant use in patients with chronic kidney disease;105 109 112 sodium bicarbonate may be an alternative if aluminum-containing phosphate binders required113 115
Cardiac glycosides	Potential for toxicity108 111 112
Chlorpropamide	Urinary alkalinization may increase renal elimination of chlorpropamide116
Diuretics, potassium-sparing	Potential for hyperkalemia and toxicity with citrate preparations containing potassium108 111 112 116
Eplerenone	Potential for hyperkalemia and toxicity with citrate preparations containing potassium116
Lithium	Urinary alkalinization may increase renal lithium clearance116
Potassium-containing drugs	Potential for hyperkalemia and toxicity with citrate preparations containing potassium108 112 116
Pseudoephedrine	Urinary alkalinization may decrease elimination of pseudoephedrine116	Pseudoephedrine dosage reduction may be needed116
Quinidine	Urinary alkalinization may decrease elimination of quinidine116	Monitor ECGs and serum quinidine concentrations if citrate therapy is initiated or discontinued in a patient receiving a stable quinidine dosage116
Salicylates	Urinary alkalinization may increase renal elimination of salicylates; possible decreased therapeutic and toxic effects of salicylates116

Citrate Salts, Citric Acid, Citric Acid Monohydrate, Potassium Citrate, Potassium Citrate Monohydrate, Sodium Citrate, Sodium Citrate and Citric Acid, Sodium Citrate Dihydrate Pharmacokinetics

Distribution

Extent

Not known whether potassium citrate is distributed into milk.¹¹⁰

Elimination

Metabolism

Metabolism of citrates appears to be associated with bicarbonate formation. ^{105 108 109 111 a}

Elimination Route

Citrates are excreted in urine, mainly as metabolites; <5% of an oral dose is excreted in the urine unchanged.^{104 105 108 109 a}

Stability

Storage

Oral

Solution

Potassium citrate and citric acid oral solutions (e.g., Cytra-K): Tight, light-resistant containers at 20–25°C; protect from excessive heat or freezing.^{107 111}

Potassium citrate and citric acid for oral solution (Cytra-K Crystals): Protect from excessive heat or freezing.¹⁰⁸

Sodium citrate and citric acid oral solution (Oracit): Well-closed containers at 15–30°C.¹⁰⁴

Sodium citrate and citric acid oral solution (Cytra-2): Tight, light-resistant containers at 20–25°C; protect from freezing.¹⁰⁵

Sodium citrate and citric acid oral solution (Bicitra): Tight containers; protect from freezing or excessive heat.¹⁰⁹

Tricitrates oral solution (e.g., Cytra-3): Tight, light-resistant containers at 20–25°C; protect from excessive heat or freezing.^{106 112}

Compatibility

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

Oral

Solution

May use sodium citrate and citric acid as a buffer to maintain an approximate pH in various extemporaneous formulations.^a In general, the addition of the following concentration of the drugs should produce a solution buffered to the approximate pH listed:

Adapted from Schumacher GE. Buffer formulations. Am J Hosp Pharm. 1966; 23:628-9.

Citrate Buffer

pH	Citric Acid Monohydrate g/L	Sodium Citrate Dihydrate g/L
2.5	64.4	7.8
3.0	57.4	17.6
3.5	47.6	31.4
4.0	40.6	41.2
4.5	30.8	54.9
5.0	19.6	70.6
5.5	9.8	84.3
6.0	4.2	92.1
6.5	1.8	95.6

ActionsActions

• 
  

  Potassium citrate is absorbed and then appears to be metabolized to potassium bicarbonate, resulting in systemic alkalinization.^{108 111}

  
  


• 
  

  Sodium citrate is absorbed and then appears to be metabolized to sodium bicarbonate, resulting in systemic alkalinization.^{105 109}

  
  


• 
  

  Sodium citrate has anticoagulant activity;^a prevents the clotting of blood by forming an undissociated calcium citrate complex, making calcium unavailable to the clotting mechanism. ^a Anticoagulant sodium citrate solution, when added to blood, prevents the clotting of blood and the crenation or swelling of cells.^a Sterile solution is used as an anticoagulant for banked blood for transfusion and to prepare citrated human plasma and blood for fractionation.^a

  
  


• 
  

  Sodium citrate prevents the curdling of milk by rennin; has been used to alter cow’s milk so that large hard curds are not formed in the stomach of feeding infants.^a

  
  

Advice to Patients

• 
  

  Importance of following instructions for dosage preparation, including reconstitution and/or dilution recommendations.^{104 105 106 107 108 109} (See Oral Administration under Dosage and Administration.)

  
  


• 
  

  Importance of taking drugs only as prescribed, unless otherwise instructed by a clinician.^{105 106 107 109 111}

  
  


• 
  

  Importance of taking doses after meals to avoid saline laxative effect.^{104 105 106 107 108 109 111 112}

  
  


• 
  

  Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.^{104 105 106 107 108 109}

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.^{105 106 107 108 109}

  
  


• 
  

  Importance of informing patients of other important precautionary information.^{104 105 106 107 108 109} (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

Potassium Citrate and Citric Acid

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	For solution	Potassium Citrate Monohydrate 3300 mg and Citric Acid Monohydrate 1002 mg per packet	Cytra-K Crystals	Cypress
	Solution	Potassium Citrate Monohydrate 1100 mg/5 mL and Citric Acid Monohydrate 334 mg/5 mL*	Cytra-K	Cypress
			Potassium Citrate Monohydrate and Citric Acid Monohydrate Solution

Sodium Citrate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Bulk	Powder

Sodium Citrate and Citric Acid

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Solution (Shohl’s Solution)	Hydrous Sodium Citrate 490 mg/5 mL and Citric Acid 640 mg/5 mL	Oracit	Carolina Medical
		Sodium Citrate Dihydrate 500 mg/5 mL and Citric Acid Monohydrate 334 mg/5 mL	Bicitra	Ortho-McNeil
			Cytra-2	Cypress

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

Tricitrates

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Solution	Citric Acid Monohydrate 334 mg/5 mL, Potassium Citrate Monohydrate 550 mg/5 mL, and Sodium Citrate Dihydrate 500 mg/5 mL*	Cytra-3 Syrup	Cypress
			Citric Acid Monohydrate, Potassium Citrate Monohydrate, and Sodium Citrate Dihydrate Solution

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 April 2009. 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

Only references cited for selected revisions after 1984 are available electronically.

100. Alza Pharmaceuticals. Polycitra-K (potassium citrate and citric acid for oral solution) crystals prescribing information. Mountain View, CA; Feb 2000. From the Alza website ()

101. Alza Pharmaceuticals. Polycitra-K (potassium citrate and citric acid) oral solution prescribing information. Mountain View, CA; Apr 1998. From the Alza website ()

102. Alza Pharmaceuticals. Bicitra (potassium citrate and citric acid) oral solution prescribing information. Mountain View, CA; Apr 1998. From the Alza website ()

103. Alza Pharmaceuticals. Polycitra-LC and syrup (tricitrates) oral solution prescribing information. Mountain View, CA; Apr 1998. From the Alza website ()

104. Carolina Medical Products. ORACIT oral citrate (Shohl’s) solution prescribing information. Farmville, NC; 1986 May.

105. Cypress Pharmaceuticals. Cytra-2(sodium citrate and citric acid) oral solution prescribing information.Madison, MS; 2006 Mar.

106. Cypress Pharmaceuticals. Cytra-3 (potassium citrate, sodium citrate, and citric acid) oral syrup prescribing information.Madison, MS; 1998 Jul.

107. Cypress Pharmaceuticals. Cytra-K Oral Solution (potassium citrate and citric acid) prescribing information. Madison, MS; 1998 Jun.

108. Cypress Pharmaceuticals. Cytra-K Crystals (potassium citrate and citric acid for oral solution) prescribing information. Madison, MS; 1997 Dec.

109. Ortho-McNeil Pharmaceutical. Bicitra (sodium citrate and citric acid) oral solution prescribing information. Raritan, NJ; 2005 Mar.

110. Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. Lippincott Williams & Wilkins: Philadelphia, PA; 2008.

111. Pai Pharmaceutical Associates. Potassium citrate and citric acid oral solution prescribing information. Greenville, SC; 2000 Jun.

112. Pai Pharmaceutical Associates. Potassium citrate, sodium citrate, and citric acid oral solution prescribing information. Greenville, SC; 1999 Dec.

113. Rudy D, Sica DA, Comstock T et al. Aluminum-citrate interaction in end-stage renal disease. Int J Artif Organs. 1991; 14:625-9. [PubMed 1748529]

114. KDOQI, National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in children with chronic kidney disease. Am J Kidney Dis. 2005; 46(4 Suppl 1):S1-21. Available at . Accessed 2008 Jun 13.

115. Walker JA, Sherman RA, Cody RP. The effect of oral bases on enteral aluminum absorption. Arch Intern Med. 1990; 150:2037-9. [PubMed 2171446]

116. Tatro DS, ed. Drug interaction facts. St. Louis: Wolters Kluwer Health; 2008 (Apr):202he, 313b, 470, 579, 580, 608, 620b, 672, 684a.

a. AHFS Drug Information 2008. McEvoy GK, ed. Citrate Salts. Bethesda, MD: American Society of Health-System Pharmacists; 2008: 2710-11.

Idursulfase

In the US, Idursulfase (idursulfase systemic) is a member of the drug class lysosomal enzymes and is used to treat Mucopolysaccharidosis Type II.

US matches:

• Idursulfase


• Idursulfase Intravenous

Scheme

Rec.INN

ATC (Anatomical Therapeutic Chemical Classification)

A16AB09

CAS registry number (Chemical Abstracts Service)

0050936-59-9

Chemical Formula

C2689-H4057-N699-O792-S14

Molecular Weight

59297

Therapeutic Category

Enzyme

Chemical Names

α-L-iduronate sulfate sulfatase (WHO)

Sulfatase, L-idurono- (USAN)

Foreign Names

• Idursulfaseum (Latin)
• Idursulfase (German)
• Idursulfase (French)
• Idursulfasa (Spanish)

Generic Names

• Idursulfase (OS: BAN, USAN)
• EC 3.1.6.13 (IS: TranskaryoticT)
• I2S (IS: Shire)
• I2S CNS (IS)
• Idusulfase (IS)
• Sulfoiduronate sulfohydrolase (IS)

Brand Names

• Elaprase
  Drac, Switzerland; LCA, Belgium; Paladin, Canada; Shire, Austria; Shire, France; Shire, Greece; Shire, Netherlands; Shire, United States; Shire HGT, Germany; Shire Human, Spain; Shire Human, Sweden; Shire Human Genetic, United Kingdom; Shire Human Genetic Therapies, Denmark; Shire Human Genetic Therapies, Finland; Solpharm, Croatia (Hrvatska)

International Drug Name Search

Glossary

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

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

Chlordiazepoxide

Dosage Form: capsule
Chlordiazepoxide HYDROCHLORIDE CAPSULES USP CIV

Rx only

Chlordiazepoxide Description

Chlordiazepoxide hydrochloride is the prototype for the benzodiazepine compounds. It is a versatile therapeutic agent of proven value for the relief of anxiety. Chlordiazepoxide hydrochloride is among the safer of the effective psychopharmacologic compounds available, as demonstrated by extensive clinical evidence.

Chlordiazepoxide hydrochloride is 7-chloro-2- (methylamino)-5-phenyl-3H-1, 4-benzodiazepine 4-oxide hydrochloride. A white to practically white crystalline substance, it is soluble in water. It is unstable in solution and the powder must be protected from light. The structural formula is:

C16H14ClN3O • HCl M.W. 336.22

Each capsule, for oral administration, contains either 5 mg, 10 mg or 25 mg of Chlordiazepoxide hydrochloride USP and has the following inactive ingredients: anhydrous lactose, D&C yellow no. 10, FD&C blue no. 1, FD&C blue no. 1 aluminum lake, gelatin, hydrogenated vegetable oil, microcrystalline cellulose, pharmaceutical glaze, and titanium dioxide. The 5 mg and 25 mg also contains D&C yellow no. 10 aluminum lake, FD&C blue no. 2 aluminum lake, FD&C red no. 40 aluminum lake, propylene glycol, and synthetic black iron oxide. In addition, the 5 mg contains D&C red no. 33 and the 10 mg also contains butyl paraben, edetate calcium disodium, dimethyl polysiloxane, ethylene glycol monoethyl ether, FD&C red no. 40, methyl paraben, propyl paraben, sodium, sodium lauryl sulfate, sodium propionate, and soya lecithin.

CLINICAL PHARMACOLOGY

Chlordiazepoxide HCl has antianxiety, sedative, appetite-stimulating and weak analgesic actions. The precise mechanism of action is not known. The drug blocks EEG arousal from stimulation of the brain stem reticular formation. It takes several hours for peak blood levels to be reached and the half-life of the drug is between 24 and 48 hours. After the drug is discontinued plasma levels decline slowly over a period of several days. Chlordiazepoxide is excreted in the urine, with 1% to 2% unchanged and 3% to 6% as conjugate.

Animal Pharmacology

The drug has been studied extensively in many species of animals and these studies are suggestive of action on the limbic system of the brain, which recent evidence indicates is involved in emotional responses.

Hostile monkeys were made tame by oral drug doses which did not cause sedation. Chlordiazepoxide HCl revealed a “taming” action with the elimination of fear and aggression. The taming effect of Chlordiazepoxide HCl was further demonstrated in rats made vicious by lesions in the septal area of the brain. The drug dosage which effectively blocked the vicious reaction was well below the dose which caused sedation in these animals.

The LD50 of parenterally administered Chlordiazepoxide HCl was determined in mice (72 hours) and rats (5 days), and calculated according to the method of Miller and Tainter, with the following results: mice, IV, 123 ± 12 mg/kg; mice, IM, 366 ± 7 mg/kg; rats, IV, 120 ± 7 mg/kg; rats, IM, > 160 mg/kg.

Effects on Reproduction

Reproduction studies in rats fed 10, 20 and 80 mg/kg daily and bred through one or two matings showed no congenital anomalies, nor were there adverse effects on lactation of the dams or growth of the newborn. However, in another study at 100 mg/kg daily there was noted a significant decrease in the fertilization rate and a marked decrease in the viability and body weight of off-spring which may be attributable to sedative activity, thus resulting in lack of interest in mating and lessened maternal nursing and care of the young. One neonate in each of the first and second matings in the rat reproduction study at the 100 mg/kg dose exhibited major skeletal defects. Further studies are in progress to determine the significance of these findings.

Indications and Usage for Chlordiazepoxide

Chlordiazepoxide HCl capsules USP are indicated for the management of anxiety disorders or for the short term relief of symptoms of anxiety, withdrawal symptoms of acute alcoholism, and preoperative apprehension and anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic.

The effectiveness of Chlordiazepoxide HCl capsules USP in long term use, that is, more than 4 months, has not been assessed by systematic clinical studies. The physician should periodically reassess the usefulness of the drug for the individual patient.

Contraindications

Chlordiazepoxide HCl capsules are contraindicated in patients with known hypersensitivity to the drug.

Warnings

Chlordiazepoxide HCl may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a vehicle or operating machinery. Similarly, it may impair mental alertness in children. The concomitant use of alcohol or other central nervous system depressants may have an additive effect. PATIENTS SHOULD BE WARNED ACCORDINGLY.

Usage in Pregnancy

An increased risk of congenital malformations associated with the use of minor tranquilizers (Chlordiazepoxide, diazepam and meprobamate) during the first trimester of pregnancy has been suggested in several studies. Because use of these drugs is rarely a matter of urgency, their use during this period should almost always be avoided. The possibility that a woman of childbearing potential may be pregnant at the time of institution of therapy should be considered. Patients should be advised that if they become pregnant during therapy or intend to become pregnant they should communicate with their physicians about the desirability of discontinuing the drug.

Withdrawal symptoms of the barbiturate type have occurred after the discontinuation of benzodiazepines (see DRUG ABUSE AND DEPENDENCE section).

Precautions

In elderly and debilitated patients, it is recommended that the dosage be limited to the smallest effective amount to preclude the development of ataxia or oversedation (10 mg or less per day initially, to be increased gradually as needed and tolerated). In general, the concomitant administration of Chlordiazepoxide HCl and other psychotropic agents is not recommended. If such combination therapy seems indicated, careful consideration should be given to the pharmacology of the agents to be employed — particularly when the known potentiating compounds such as MAO inhibitors and phenothiazines are to be used. The usual precautions in treating patients with impaired renal or hepatic function should be observed.

Paradoxical reactions, e.g., excitement, stimulation and acute rage, have been reported in psychiatric patients and in hyperactive aggressive pediatric patients, and should be watched for during Chlordiazepoxide HCl therapy. The usual precautions are indicated when Chlordiazepoxide HCl is used in the treatment of anxiety states where there is any evidence of impending depression; it should be borne in mind that suicidal tendencies may be present and protective measures may be necessary. Although clinical studies have not established a cause and effect relationship, physicians should be aware that variable effects on blood coagulation have been reported very rarely in patients receiving oral anticoagulants and Chlordiazepoxide HCl. In view of isolated reports associating Chlordiazepoxide with exacerbation of porphyria, caution should be exercised in prescribing Chlordiazepoxide to patients suffering from this disease.

Pediatric Use

Because of the varied response of pediatric patients to CNS-acting drugs, therapy should be initiated with the lowest dose and increased as required (see DOSAGE AND ADMINISTRATION). Since clinical experience with Chlordiazepoxide HCl in pediatric patients under 6 years of age is limited, use in this age group is not recommended. Hyperactive aggressive pediatric patients should be monitored for paradoxical reactions to Chlordiazepoxide HCl (see PRECAUTIONS).

Information for Patients

To assure the safe and effective use of benzodiazepines, patients should be informed that, since benzodiazepines may produce psychological and physical dependence, it is advisable that they consult with their physician before either increasing the dose or abruptly discontinuing this drug.

Adverse Reactions

The necessity of discontinuing therapy because of undesirable effects has been rare. Drowsiness, ataxia and confusion have been reported in some patients — particularly the elderly and debilitated. While these effects can be avoided in almost all instances by proper dosage adjustment, they have occasionally been observed at the lower dosage ranges. In a few instances syncope has been reported.

Other adverse reactions reported during therapy include isolated instances of skin eruptions, edema, minor menstrual irregularities, nausea and constipation, extrapyramidal symptoms, as well as increased and decreased libido. Such side effects have been infrequent, and are generally controlled with reduction of dosage. Changes in EEG patterns (low-voltage fast activity) have been observed in patients during and after Chlordiazepoxide HCl treatment.

Blood dyscrasias (including agranulocytosis), jaundice and hepatic dysfunction have occasionally been reported during therapy. When Chlordiazepoxide HCl treatment is protracted, periodic blood counts and liver function tests are advisable.

Drug Abuse and Dependence

Chlordiazepoxide hydrochloride capsules are classified by the Drug Enforcement Administration as a Schedule IV controlled substance.

Withdrawal symptoms, similar in character to those noted with barbiturates and alcohol (convulsions, tremor, abdominal and muscle cramps, vomiting and sweating), have occurred following abrupt discontinuance of Chlordiazepoxide. The more severe withdrawal symptoms have usually been limited to those patients who had received excessive doses over an extended period of time. Generally milder withdrawal symptoms (e.g., dysphoria and insomnia) have been reported following abrupt discontinuance of benzodiazepines taken continuously at therapeutic levels for several months. Consequently, after extended therapy, abrupt discontinuation should generally be avoided and a gradual dosage tapering schedule followed. Addiction-prone individuals (such as drug addicts or alcoholics) should be under careful surveillance when receiving Chlordiazepoxide or other psychotropic agents because of the predisposition of such patients to habituation and dependence.

Overdosage

Manifestations of Chlordiazepoxide overdosage includes somnolence, confusion, coma and diminished reflexes. Respiration, pulse and blood pressure should be monitored, as in all cases of drug overdosage, although, in general, these effects have been minimal following Chlordiazepoxide HCl overdosage. General supportive measures should be employed, along with immediate gastric lavage. Intravenous fluids should be administered and an adequate airway maintained. Hypotension may be combated by the use of norepinephrine or metaraminol. Dialysis is of limited value. There have been occasional reports of excitation in patients following Chlordiazepoxide HCl overdosage; if this occurs barbiturates should not be used. As with the management of intentional overdosage with any drug, it should be borne in mind that multiple agents may have been ingested.

Flumazenil, a specific benzodiazepine-receptor antagonist, is indicated for the complete or partial reversal of the sedative effects of benzodiazepines and may be used in situations when an overdose with a benzodiazepine is known or suspected. Prior to the administration of flumazenil, necessary measures should be instituted to secure airway, ventilation and intravenous access. Flumazenil is intended as an adjunct to, not as a substitute for, proper management of benzodiazepine overdose. Patients treated with flumazenil should be monitored for resedation, respiratory depression and other residual benzodiazepine effects for an appropriate period after treatment. The prescriber should be aware of a risk of seizure in association with flumazenil treatment, particularly in long term benzodiazepine users and in cyclic antidepressant overdose. The complete flumazenil package insert, including CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS, should be consulted prior to use.

Chlordiazepoxide Dosage and Administration

Because of the wide range of clinical indications for Chlordiazepoxide HCl, the optimum dosage varies with the diagnosis and response of the individual patient. The dosage, therefore, should be individualized for maximum beneficial effects.

ADULTS	USUAL DAILY DOSE
Relief of Mild and Moderate Anxiety Disorders and Symptoms of Anxiety	5 mg or 10 mg, 3 or 4 times daily
Relief of Severe Anxiety Disorders and Symptoms of Anxiety	20 mg or 25 mg, 3 or 4 times daily
Geriatric Patients, or in the presence of debilitating disease.	5 mg, 2 to 4 times daily

Preoperative Apprehension and Anxiety

On days preceding surgery, 5 to 10 mg orally, 3 or 4 times daily. If used as preoperative medication, 50 to 100 mg IM* 1 hour prior to surgery.

PEDIATRIC PATIENTS	USUAL DAILY DOSE
Because of the varied response of pediatric patients to CNS-acting drugs, therapy should be initiated with the lowest dose and increased as required. Since clinical experience in pediatric patients under 6 years of age is limited, the use of the drug in this age group is not recommended.	5 mg, 2 to 4 times daily (may be increased in some pediatric patients to 10 mg, 2 to 3 times daily)

For the relief of withdrawal symptoms of acute alcoholism, the parenteral form* is usually used initially. If the drug is administered orally, the suggested initial dose is 50 to 100 mg, to be followed by repeated doses as needed until agitation is controlled — up to 300 mg per day. Dosage should then be reduced to maintenance levels.

*See package insert for Injectable Chlordiazepoxide HCl.

How is Chlordiazepoxide Supplied

Chlordiazepoxide Hydrochoride Capsules USP, 5 mg are available as a two-piece hard gelatin capsule with an aqua green opaque cap and a yellow opaque body filled with white powder, imprinted in black ink barr 158, packaged in bottles of 100 and 500 capsules.

Chlordiazepoxide Hydrochloride Capsules USP, 10 mg are available as a two-piece hard gelatin capsule with a black opaque cap and a green opaque body filled with white powder, imprinted in white ink barr 033, packaged in bottles of 100 and 1000 capsules.

Chlordiazepoxide Hydrochloride Capsules USP, 25 mg are available as a two-piece hard gelatin capsule with an aqua green opaque cap and a white opaque body filled with white powder, imprinted in black ink barr 159, available in bottles of 100 and 500 capsules.

Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature] in a dry place.

KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

TEVA PHARMACEUTICALS USA

Sellersville, PA 18960

Rev. A 8/2011

PRINCIPAL DISPLAY PANEL

Chlordiazepoxide Hydrochloride Capsules USP 5 mg 100s Label Text

NDC 0555-0158-02

Chlordiazepoxide

HYDROCHLORIDE

Capsules USP

5 mg

Rx only

100 CAPSULES

TEVA

PRINCIPAL DISPLAY PANEL

Chlordiazepoxide Hydrochloride Capsules USP 10 mg 100s Label Text

NDC 0555-0333-02

Chlordiazepoxide

HYDROCHLORIDE

Capsules USP

10 mg

Rx only

100 CAPSULES

TEVA

PRINCIPAL DISPLAY PANEL

Chlordiazepoxide Hydrochloride Capsules USP 25 mg 100s Label Text

NDC 0555-0159-02

Chlordiazepoxide

HYDROCHLORIDE

Capsules USP

25 mg

Rx only

100 CAPSULES

TEVA

Chlordiazepoxide HYDROCHLORIDE  Chlordiazepoxide hydrochloride  capsule

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0555-0158 Route of Administration ORAL DEA Schedule CIV

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Chlordiazepoxide HYDROCHLORIDE (Chlordiazepoxide) Chlordiazepoxide HYDROCHLORIDE 5 mg

Inactive Ingredients Ingredient Name Strength ALUMINUM OXIDE   ANHYDROUS LACTOSE   CELLULOSE, MICROCRYSTALLINE   D&C RED NO. 33   D&C YELLOW NO. 10   FD&C BLUE NO. 1   FD&C BLUE NO. 2   FD&C RED NO. 40   FERROSOFERRIC OXIDE   GELATIN   PROPYLENE GLYCOL   SHELLAC   TITANIUM DIOXIDE

Product Characteristics Color GREEN (aqua green) , YELLOW Score no score Shape CAPSULE Size 14mm Flavor Imprint Code barr;158 Contains

Packaging # NDC Package Description Multilevel Packaging 1 0555-0158-02 100 CAPSULE In 1 BOTTLE None 2 0555-0158-04 500 CAPSULE In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA084768	12/01/2011

Chlordiazepoxide HYDROCHLORIDE  Chlordiazepoxide hydrochloride  capsule

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0555-0033 Route of Administration ORAL DEA Schedule CIV

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Chlordiazepoxide HYDROCHLORIDE (Chlordiazepoxide) Chlordiazepoxide HYDROCHLORIDE 10 mg

Inactive Ingredients Ingredient Name Strength ALUMINUM OXIDE   ANHYDROUS LACTOSE   BUTYLPARABEN   CELLULOSE, MICROCRYSTALLINE   D&C YELLOW NO. 10   DIMETHICONE   ETHYLENE GLYCOL MONOETHYL ETHER   FD&C BLUE NO. 1   FD&C RED NO. 40   GELATIN   LECITHIN, SOYBEAN   METHYLPARABEN   PROPYLPARABEN   SHELLAC   SODIUM LAURYL SULFATE   SODIUM PROPIONATE   TITANIUM DIOXIDE

Product Characteristics Color BLACK, GREEN Score no score Shape CAPSULE Size 14mm Flavor Imprint Code barr;033 Contains

Packaging # NDC Package Description Multilevel Packaging 1 0555-0033-02 100 CAPSULE In 1 BOTTLE None 2 0555-0033-05 1000 CAPSULE In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA083116	12/01/2011

Chlordiazepoxide HYDROCHLORIDE  Chlordiazepoxide hydrochloride  capsule

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0555-0159 Route of Administration ORAL DEA Schedule CIV

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Chlordiazepoxide HYDROCHLORIDE (Chlordiazepoxide) Chlordiazepoxide HYDROCHLORIDE 25 mg

Inactive Ingredients Ingredient Name Strength ALUMINUM OXIDE   ANHYDROUS LACTOSE   CELLULOSE, MICROCRYSTALLINE   D&C YELLOW NO. 10   FD&C BLUE NO. 1   FD&C BLUE NO. 2   FD&C RED NO. 40   FERROSOFERRIC OXIDE   GELATIN   PROPYLENE GLYCOL   SHELLAC   TITANIUM DIOXIDE

Product Characteristics Color GREEN (aqua green) , WHITE Score no score Shape CAPSULE Size 14mm Flavor Imprint Code barr;159 Contains

Packaging # NDC Package Description Multilevel Packaging 1 0555-0159-02 100 CAPSULE In 1 BOTTLE None 2 0555-0159-04 500 CAPSULE In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA084769	12/01/2011

Labeler - Barr Laboratories Inc. (802716563)

Revised: 12/2011Barr Laboratories Inc.