Antivert

Generic Name: meclizine (MEK li zeen)

Brand Names: Antivert, Bonine, D-Vert, Dramamine II

What is meclizine?

Meclizine is an antihistamine that reduces the natural chemical histamine in the body.

Meclizine is used to treat or prevent nausea, vomiting, and dizziness caused by motion sickness. Meclizine is also used to treat symptoms of vertigo.

Meclizine may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about meclizine?

Use this medication exactly as directed on the label, or as prescribed by your doctor. Do not use it in larger amounts or for longer than recommended.

You should not take this medication if you are allergic to meclizine.

Before taking meclizine, tell your doctor if you have asthma or other breathing disorder, glaucoma, an enlarged prostate, or problems with urination.

Do not give this medication to a child younger than 12 years old. Meclizine can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert. Avoid drinking alcohol. It can increase some of the side effects of meclizine.

Cold or allergy medicine, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression or anxiety can add to sleepiness caused by meclizine. Avoid taking these other medications at the same time you take meclizine.

What should I discuss with my healthcare provider before taking meclizine?

You should not take this medication if you are allergic to meclizine.

Before taking meclizine, tell your doctor if you are allergic to any drugs, or if you have:

• 
  

  asthma or other breathing disorder;

  
  


• 
  

  glaucoma;

  
  


• 
  

  an enlarged prostate; or

  
  


• 
  

  problems with urination.

  
  

If you have any of these conditions, you may not be able to use this medication, or you may need a dose adjustment or special tests during treatment.

FDA pregnancy category B. Meclizine is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether meclizine passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby. Do not give this medication to a child younger than 12 years old.

How should I take meclizine?

Use this medication exactly as directed on the label, or as prescribed by your doctor. Do not use it in larger amounts or for longer than recommended.

Take meclizine with a full glass of water.

The chewable tablet may be swallowed whole, crushed, or chewed.

To prevent motion sickness, take meclizine about 1 hour before you travel or engage in activity that causes motion sickness. You may take meclizine once every 24 hours while you are traveling, to further prevent motion sickness.

To treat vertigo, you may need to take meclizine several times daily. Follow your doctor's instructions.

Meclizine can cause you to have unusual results with allergy skin tests. Tell any doctor who treats you that you are taking an antihistamine.

Store meclizine at room temperature away from moisture, heat, and light.

What happens if I miss a dose?

Since meclizine is sometimes taken only when needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to take the medicine and skip the missed dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine.

Overdose symptoms may include extreme drowsiness.

What should I avoid while taking meclizine?

Meclizine can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert. Avoid drinking alcohol. It can increase some of the side effects of meclizine.

Cold or allergy medicine, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression or anxiety can add to sleepiness caused by meclizine. Avoid taking these other medications at the same time you take meclizine.

Meclizine side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Less serious side effects may include:

• 
  

  blurred vision;

  
  


• 
  

  dry mouth;

  
  


• 
  

  constipation; or

  
  


• 
  

  dizziness, drowsiness.

  
  

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect meclizine?

There may be other drugs that can interact with meclizine. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

More Antivert resources

• Antivert Side Effects (in more detail)
• Antivert Use in Pregnancy & Breastfeeding
• Drug Images
• Antivert Drug Interactions
• Antivert Support Group
• 4 Reviews for Antivert - Add your own review/rating

• Antivert Prescribing Information (FDA)


• Antivert Consumer Overview


• Antivert MedFacts Consumer Leaflet (Wolters Kluwer)


• Meclizine Professional Patient Advice (Wolters Kluwer)


• Meclizine Prescribing Information (FDA)


• Meclizine Hydrochloride Monograph (AHFS DI)

Compare Antivert with other medications

• Motion Sickness
• Nausea/Vomiting
• Vertigo

Where can I get more information?

• Your pharmacist can provide more information about meclizine.

See also: Antivert side effects (in more detail)

Fosamax

Generic Name: Alendronate Sodium
Class: Bone Resorption Inhibitors
VA Class: HS900
Chemical Name: (4-Amino-1-hydroxybutylidene)bis-phosphonic acid, monosodium salt, trihydrate
Molecular Formula: C₄H₁₃NO₇P₂•3H₂O•Na
CAS Number: 121268-17-5

Special Alerts:

[Posted 07/21/2011] ISSUE: FDA notified healthcare professionals and patients about its ongoing review of data from published studies to evaluate whether use of oral bisphosphonate drugs is associated with an increased risk of cancer of the esophagus. FDA has not concluded that taking an oral bisphosphonate drug increases the risk of esophageal cancer. There are insufficient data to recommend endoscopic screening of asymptomatic patients. FDA will continue to evaluate all available data supporting the safety and effectiveness of bisphosphonate drugs and will update the public when more information becomes available.

BACKGROUND: Oral bisphosphonates are commonly used for the prevention and treatment of osteoporosis as well as to treat other bone diseases such as Paget’s disease. There have been conflicting findings from studies evaluating the risk of esophageal cancer. Esophagitis and other esophageal events have been reported, particularly in patients who do not follow the specific directions for use of oral bisphosphonates. See the Data Summary in the Drug Safety Communication for additional details at: .

RECOMMENDATION: Patients should talk with their healthcare professional about the benefits and risks of taking oral bisphosphonates and how long they should expect to take them. Patients should talk with their healthcare professional if they develop swallowing difficulties, chest pain, new or worsening heartburn, or have trouble or pain when swallowing. Patients should be instructed to carefully follow the directions for use of the oral bisphosphonate drug they are prescribed. For more information visit the FDA website at: and .

[Posted 10/13/2010] ISSUE: FDA is updating the public regarding information previously communicated describing the risk of atypical fractures of the thigh, known as subtrochanteric and diaphyseal femur fractures, in patients who take bisphosphonates for osteoporosis. This information will be added to the Warnings and Precautions section of the labels approved to treat osteoporosis, including alendronate (Fosamax), alendronate with cholecalciferol (Fosamax Plus D), risedronate (Actonel and Atelvia), risedronate with calcium carbonate (Actonel with Calcium), ibandronate (Boniva), tiludronate (Skelid), and zoledronic acid (Reclast) and their generic products. A Medication Guide will also be required to be given to patients when they pick up their bisphosphonate prescription.

BACKGROUND: Atypical subtrochanteric femur fractures are fractures in the bone just below the hip joint. Diaphyseal femur fractures occur in the long part of the thigh bone. These fractures are very uncommon and appear to account for less than 1% of all hip and femur fractures overall. Although it is not clear if bisphosphonates are the cause, these unusual femur fractures have been predominantly reported in patients taking bisphosphonates.

RECOMMENDATIONS: Patients should continue to take their medication unless told to stop by their healthcare professional. FDA recommends that healthcare professionals should discontinue potent antiresorptive medications (including bisphosphonates) in patients who have evidence of a femoral shaft fracture. For more information visit the FDA website at: and .

[Posted 03/11/2010] FDA notified healthcare professionals and patients that at this point, the data that FDA has reviewed have not shown a clear connection between bisphosphonate use and a risk of atypical subtrochanteric femur fractures. FDA is working with outside experts, including members of the recently convened American Society of Bone and Mineral Research Subtrochanteric Femoral Fracture Task Force, to gather more information and evaluate the issue further.

FDA recommends that healthcare professionals follow the recommendations in the drug label when prescribing oral bisphosphonates.

Patients should continue taking oral bisphosphonates unless told by their healthcare professional to stop. Patients should talk to their healthcare professional if they develop new hip or thigh pain or have any concerns with their medications. For more information visit the FDA website at: and .

[Posted 11/12/2008] FDA issued an update to the Agency’s review of safety data regarding the potential increased risk of atrial fibrillation in patients treated with a bisphosphonate drug. Bisphosphonates are a class of drugs used primarily to increase bone mass and reduce the risk for fracture in patients with osteoporosis, slow bone turnover in patients with Paget’s disease of the bone, and to treat bone metastases and lower elevated levels of blood calcium in patients with cancer. FDA reviewed data on 19,687 bisphosphonate-treated patients and 18,358 placebo-treated patients who were followed for 6 months to 3 years. The occurrence of atrial fibrillation was rare within each study, with most studies containing 2 or fewer events. Across all studies, no clear association between overall bisphosphonate exposure and the rate of serious or non-serious atrial fibrillation was observed. Additionally, increasing dose or duration of bisphosphonate therapy was not associated with an increase rate of atrial fibrillation. Healthcare professionals should not alter their prescribing patterns for bisphosphonates and patients should not stop taking their bisphosphonate medication. For more information visit the FDA website at: , and .

REMS:

FDA approved a REMS for alendronate to ensure that the benefits of a drug outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Synthetic bisphosphonate; bone resorption inhibitor.^{1 2 3 4 a}

Uses for Fosamax

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Osteoporosis

Alendronate is used for prevention of osteoporosis in postmenopausal women^{1 24 25} with risk factors for development of osteoporosis.^{1 41 46 47 50 51 52 53 62} Risk factors include premature ovarian failure; family history of osteoporosis; small, slim body frame; endocrine disorders (e.g., thyrotoxicosis, hyperparathyroidism, Cushing’s syndrome, hyperprolactinemia, insulin-dependent diabetes mellitus); cigarette smoking; excessive alcohol use; sedentary lifestyle; low body weight; moderately low body mass; low dietary calcium intake; or Caucasian or Asian race.^{1 41 46 47 50 51 52 53 62}

Alendronate is used alone or in fixed combination with cholecalciferol (vitamin D₃) for treatment of osteoporosis in postmenopausal women.^{1 2 3 5 6 7 8 10 11 12 13 a}

Alendronate is used alone or in fixed combination with cholecalciferol for treatment of osteoporosis in men.^{1 66 70 a}

Alendronate/cholecalciferol fixed combination is not recommended for treatment of vitamin D deficiency.^{a e}

Alendronate has been used concomitantly with hormone replacement therapy.^{1 68 69}

Corticosteroid-induced Osteoporosis

Alendronate is used for treatment of corticosteroid-induced osteoporosis in patients receiving corticosteroids (daily dosage ≥5–7.5 mg of prednisone).^{1 57 58 73 78}

Alendronate is used for prevention of corticosteroid-induced osteoporosis† in patients receiving corticosteroid therapy (daily dosage ≥5 mg of prednisone).^{57 58 73 78}

American College of Rheumatology considers patients receiving ≥5 mg prednisone daily for ≥3 months at risk for bone loss.⁷⁸ Recommends bisphosphonate therapy for all long-term corticosteroid-treated men, premenopausal women (with caution), and postmenopausal women with or without hormone replacement therapy (combined estrogen and progestin therapy).⁷⁸

Paget’s Disease of Bone

Alendronate is used for treatment of moderate to severe Paget’s disease of bone (osteitis deformans) in patients with serum alkaline phosphatase concentrations ≥ twice ULN or who are symptomatic or at risk for future complications.^{1 15}

Fosamax Dosage and Administration

General

• 
  

  Use adjunctively with other measures (e.g., diet, weight-bearing exercise, physical therapy, reduction in smoking, alcohol use) to retard further bone loss.^{1 41 45 78 a e}

  
  


• 
  

  Supplemental calcium and vitamin D recommended if daily dietary intake is inadequate, particularly in patients with Paget’s disease of bone or receiving corticosteroids.^{1 1 a e}

  
  


• 
  

  Supplemental vitamin D recommended in patients at increased risk for vitamin D insufficiency (e.g., >70 years of age, nursing home bound, chronically ill, with GI malabsorption syndrome) if necessary.^a (See Metabolic Effects under Cautions.)

  
  


• 
  

  Recommended intake of vitamin D is 400–800 units daily; once-weekly dose of alendronate/cholecalciferol fixed-combination preparation containing cholecalciferol 2800 or 5600 units provides the equivalent of 400 or 800 units, respectively, of vitamin D daily.^a

  
  

Administration

Oral Administration (Alendronate and Alendronate/Cholecalciferol)

Administer tablet orally upon arising with a full glass (180–240 mL) of plain water at least 30 minutes before first food, beverage, or other orally administered drug of the day.^{1 1 a} (See Food under Pharmacokinetics.)

Drink at least 60 mL (2 oz., a quarter of a cup) of water after taking the oral solution to facilitate gastric emptying.¹

Administer in an upright position (sitting or standing).^{1 a} Avoid lying down for at least 30 minutes following administration and until after the first food of the day.^{1 a} (See GI Effects under Cautions.)

Avoid administering at bedtime or before arising for the day.^{1 20 a}

Do not suck or chew tablets; potential oropharyngeal irritation.^{20 1 a e}

Avoid any other medications, including calcium supplements or antacids, for 30 minutes after alendronate is administered.^{1 a} (See Antacids or Mineral Supplements Containing Divalent Cations under Interactions.)

If a weekly dose is missed, administer missed dose the morning after it is remembered, followed by resumption of the regular weekly schedule.^{1 a} However, do not take two 70-mg tablets on the same day.^{1 a}

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Available as alendronate sodium; dosage expressed in terms of alendronate.^{1 a}

Adults

Osteoporosis

Prevention of Postmenopausal Osteoporosis

Oral

Alendronate 5 mg once daily or 35 mg once weekly.¹

Treatment of Osteoporosis

Oral

Alendronate 10 mg once daily or 70 mg once weekly in men and postmenopausal women.¹

Alendronate/cholecalciferol fixed-combination: Usually, alendronate 70 mg and cholecalciferol 5600 units once weekly in men and postmenopausal women.^a Alternatively, alendronate 70 mg and cholecalciferol 2800 units once weekly.^a

Corticosteroid-induced Osteoporosis

Prevention of Corticosteroid-induced Osteoporosis†

Oral

Alendronate 5 mg once daily in postmenopausal women receiving hormone replacement therapy (HRT), premenopausal women, and men.^{73 78}

Alendronate 10 mg once daily in postmenopausal women not receiving HRT.⁷⁸

Continue alendronate as long as patient continues to receive corticosteroid therapy.⁷⁸

Treatment of Corticosteroid-induced Osteoporosis

Oral

Alendronate 5 mg once daily in postmenopausal women receiving HRT, premenopausal women, and men.^{1 73 78}

Alendronate 10 mg once daily in postmenopausal women not receiving HRT.^{1 78}

Continue alendronate as long as patient continues to receive corticosteroid therapy.⁷⁸

Paget’s Disease of Bone

Oral

Alendronate 40 mg once daily for 6 months.¹

Consider retreatment after a 6-month posttreatment evaluation period if relapse occurs (i.e., increased serum alkaline phosphatase concentration) or if initial treatment failed to normalize serum alkaline phosphatase concentrations.¹

Special Populations

Renal Impairment

No dosage adjustment required in patients with mild to moderate impairment (Cl_cr 35–60 mL/minute); not recommended in patients with severe impairment (Cl_cr <35 mL/minute).^{1 a}

Geriatric Patients

No dosage adjustment required.^a

Cautions for Fosamax

Contraindications

• 
  

  Esophageal abnormalities that delay esophageal emptying (e.g., stricture, achalasia).^{1 20 21 23 a}

  
  


• 
  

  Patients at increased risk of aspiration should not receive alendronate oral solution.¹

  
  


• 
  

  Inability to stand or sit upright for at least 30 minutes.^{1 20 21 23 a}

  
  


• 
  

  Hypocalcemia.^{1 a}

  
  


• 
  

  Known hypersensitivity to alendronate or any ingredient in the formulation.^{1 a}

  
  

Warnings/Precautions

Warnings

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

GI Effects

Possible severe adverse esophageal effects (e.g., esophagitis, esophageal ulcers, erosions, strictures, perforation).^{1 16 18 20 21 23 a} Monitor for any manifestations^{1 16 18 20 21 23 a} and discontinue if dysphagia, odynophagia, new or worsening heartburn, or retrosternal pain occurs.^{1 20 23 a}

Cautious use recommended in patients with history of upper GI disease (e.g., dysphagia, esophageal diseases, gastritis, duodenitis, ulcers).^{1 20 23 a} Gastric and duodenal ulcers (some severe and with complications) reported in postmarketing surveillance.^{1 a}

General Precautions

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Diagnosis

Consider other possible causes of osteoporosis before beginning alendronate.^{1 a}

Metabolic Effects

Possible asymptomatic decreases in serum calcium and phosphate concentrations, particularly in patients with Paget’s disease and in those receiving corticosteroids; ensure adequate calcium and vitamin D intake.^{1 a}

Correct hypocalcemia and other disorders affecting mineral metabolism (e.g., vitamin D deficiency) before initiation of alendronate therapy;^{1 a} administer supplemental calcium and vitamin D if daily dietary intake is inadequate.^{1 26 27 28 29 38 46 47 48 51 52 53} Monitor serum calcium and monitor for symptoms of hypocalcemia during therapy.^a

Fixed combination of alendronate and cholecalciferol (vitamin D₃) is not recommended for treatment of vitamin D deficiency (i.e., 25-hydroxyvitamin D concentration <9 ng/mL).^a Patients at risk for vitamin D insufficiency (e.g., GI malabsorption syndromes) may require higher doses of vitamin D supplementation; consider measurement of 25-hydroxyvitamin D.^a

Vitamin D₃ supplementation may increase risk of hypercalcemia and/or hypercalciuria in patients with diseases associated with unregulated overproduction of 1,25-dihydroxyvitamin D (e.g., leukemia, lymphoma, sarcoidosis).^a Monitor urine and serum calcium in these patients.^a

Musculoskeletal Effects

Severe and occasionally incapacitating bone, joint, and/or muscle pain, especially in postmenopausal women, has been reported in postmarketing surveillance.^{a f} Time to onset varied from 1 day to several months after treatment initiation.^{a f} If severe symptoms occur, discontinue drug.^a Such pain improves following discontinuance, but may recur upon subsequent rechallenge with the same drug or another bisphosphonate.^{a f}

Osteonecrosis of the jaw has been reported principally in cancer patients receiving IV bisphosphonates.^{a f} Most cases were associated with tooth extraction and/or local infection, often with delayed healing, but some cases occurred in patients with postmenopausal osteoporosis receiving oral therapy.^{a f} Known risk factors include cancer, chemotherapy, radiation therapy, corticosteroids, poor oral hygiene, preexisting dental disease, anemia, coagulopathy, and infection.^{a f}

If osteonecrosis of the jaw develops, consult an oral surgeon for treatment.^{a f} Dental surgery may exacerbate condition.^{a f}

In patients requiring dental procedures, no data are available to suggest whether discontinuance of therapy prior to procedure reduces the risk of osteonecrosis of the jaw.^{a f} Base management of patients requiring dental treatment on an individual assessment of risks and benefits.^{a f}

Use of Fixed Combinations

When alendronate is used in fixed combination with cholecalciferol, consider the cautions, precautions, and contraindications associated with cholecalciferol.^{a b}

Corticosteroid-induced Osteoporosis

Measure bone mineral density at initiation of therapy and after 6–12 months of concomitant use with corticosteroids.¹

Specific Populations

Pregnancy

Alendronate alone or in fixed combination with cholecalciferol: Category C.^{1 a}

Lactation

Not known whether alendronate is distributed into milk.^{1 a} Caution if used in nursing women.^{1 a}

Pediatric Use

Safety and efficacy not established.^{1 a}

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.^{1 a}

Renal Impairment

Decreased clearance of alendronate likely.^{1 a} Use not recommended in patients with severe renal insufficiency (Cl_cr <35 mL/minute).^{1 a}

Common Adverse Effects

Abdominal pain.^{1 a}

Interactions for Fosamax

Antacids or Mineral Supplements Containing Divalent Cations

Potential decreased alendronate absorption when administered with divalent cations (e.g., calcium).^{1 a}

Other Oral Medications

Potential decreased alendronate absorption when administered concomitantly with other oral medications.^f Administer alendronate ≥30 minutes prior to other oral medications.^f

Specific Drugs

Drug	Interaction	Comments
Antacids (calcium)	May interfere with absorption of alendronatea	Wait at least ≥30 minutes after taking alendronate before taking any other oral medicationsa
Hormone replacement therapy (estrogens; estrogens and progestins)	Potential increased effects on bone mineral density1 68 69
NSAIAs (e.g., aspirin)	Aspirin increased GI toxicity in clinical studies; no increase in toxicity with concomitant NSAIAs in one study1 a	Use caution1 a
Prednisone	No change in alendronate bioavailability1 a
Ranitidine	IV ranitidine doubled alendronate bioavailability1 a

Fosamax Pharmacokinetics

Absorption

Bioavailability

Oral bioavailability of alendronate in women and men is 0.64 and 0.59%, respectively.^{1 a}

Bioavailability of alendronate sodium tablets and oral solution equivalent.¹

Bioavailability of conventional tablets and fixed-combination tablets containing cholecalciferol (2800 and 5600 units) equivalent.^a

Onset

Decrease in bone resorption rate evident as early as 1 month.^{1 a}

Food

Alendronate bioavailability decreased by 40% when administered 0.5–1 hour prior to a meal, and by 60% when administered with coffee or orange juice.^{1 a} Bioavailability is negligible whether administered with or up to 2 hours after a meal.^{1 a}

Distribution

Extent

Alendronate is widely distributed after oral administration.^c Subsequently, redistributes rapidly to skeletal tissues.^{c a} Mean steady-state volume of distribution, exclusive of bone, is ≥28 L.^{1 a c}

Plasma Protein Binding

Alendronate: Approximately 78%.^{1 a}

Elimination

Metabolism

No evidence of metabolism of alendronate.^{1 c}

Elimination Route

Urinary excretion is the sole means of elimination of alendronate.^{1 3 a b}

Half-life

Terminal half-life of alendronate >10 years, reflecting release from bone.^{1 2 3 4 11 a}

Special Populations

In patients with renal impairment, clearance of alendronate likely to be reduced.^{1 a} Somewhat greater accumulation in bone expected.^{1 a}

Stability

Storage

Oral

Tablets

Alendronate: Tight containers at 15–30°C.¹

Alendronate/cholecalciferol fixed combination: 20–25°C (may be exposed to 15–30°C).^a Keep tablets in sealed blisters until immediately before use.^a Protect from moisture and light.^a

Oral Solution

Alendronate: 15–30°C.¹ Do not freeze.¹

Actions

• 
  

  Alendronate incorporates into bone and selectively inhibits osteoclast-mediated bone resorption in a dose-dependent manner.^{1 2 3 4 5 8 9 10}

  
  


• 
  

  Alendronate increases bone mineral density.^{1 8 24 58 66 69 70 72 73 74 78 a}

  
  


• 
  

  Pharmacologically inactive while incorporated into bone matrix.^{1 2 3 4 11 a} Continuous administration required for activity.^{1 2 3 4 11 a}

  
  

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

• 
  

  Importance of providing a copy of the manufacturer’s patient information.^{1 17 20 21 23 a}

  
  


• 
  

  Importance of correct administration (e.g., avoiding foods and beverages other than plain water, not lying down for ≥30 minutes following administration, avoiding administering at bedtime or before arising for the day).^{1 20 a e}

  
  


• 
  

  Importance of swallowing tablets whole, without chewing or sucking.^{20 a e}

  
  


• 
  

  Importance of discontinuing and informing clinician if symptoms of esophageal disease (e.g., difficulty or pain on swallowing; retrosternal, abdominal or esophageal pain; new or worsening heartburn) develop.^{1 20 23 a e}

  
  


• 
  

  Importance of adhering to recommended lifestyle modifications (e.g., weight-bearing exercise, calcium and vitamin D consumption, avoidance of excessive cigarette smoking and/or alcohol consumption).^{1 a e}

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{1 a}

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.^{1 a}

  
  


• 
  

  Importance of advising patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

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

Alendronate (Fosamax) for the treatment of Paget’s disease of bone is available only through Paget’s Patient Support Program with Pharma Care Specialty Pharmacy (800-238-7828 ext. 58197) distribution system for the 40-mg dosage regimen.^d

Alendronate Sodium

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Solution	70 mg/75 mL (of alendronate)	Fosamax	Merck
	Tablets	5 mg (of alendronate)	Fosamax	Merck
		10 mg (of alendronate)	Fosamax	Merck
		35 mg (of alendronate)	Fosamax	Merck
		40 mg (of alendronate)	Fosamax	Merck
		70 mg (of alendronate)	Fosamax	Merck

Alendronate Sodium and Cholecalciferol

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	70 mg (of alendronate) and Cholecalciferol 2800 units	Fosamax Plus D	Merck
		70 mg (of alendronate) and Cholecalciferol 5600 units	Fosamax Plus D	Merck

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 10/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Alendronate Sodium 10MG Tablets (TEVA PHARMACEUTICALS USA): 100/$240.00 or 300/$679.95

Alendronate Sodium 40MG Tablets (TEVA PHARMACEUTICALS USA): 30/$179.99 or 90/$489.95

Alendronate Sodium 5MG Tablets (TEVA PHARMACEUTICALS USA): 100/$255.98 or 300/$729.91

Alendronate Sodium 70MG Tablets (TEVA PHARMACEUTICALS USA): 4/$13.99 or 12/$20.99

Alendronate Sodium 70MG Tablets (TEVA PHARMACEUTICALS USA): 20/$29.99 or 60/$69.97

Fosamax 10MG Tablets (MERCK SHARP & DOHME): 30/$95.12 or 90/$262.94

Fosamax 35MG Tablets (MERCK SHARP & DOHME): 4/$87.66 or 12/$252.29

Fosamax 5MG Tablets (MERCK SHARP & DOHME): 30/$91.92 or 90/$265.31

Fosamax 70MG Tablets (MERCK SHARP & DOHME): 4/$101.99 or 12/$288.97

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 October 27, 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

1. Merck. Fosamax (alendronate sodium) tablets prescribing information. West Point, PA; 2004 Apr.

2. Inzerillo MT, Caspi A. Alendronate: an investigational agent for the prevention and treatment of osteoporosis. P & T. 1994; 19:851-2.

3. Kanis JA, Gertz BJ, Singer F et al. Rationale for the use of alendronate in osteoporosis. Osteoporos Int. 1995; 5:1-13. [PubMed 7703618]

4. Gertz BJ, Holland SD, Kline WF et al. Clinical pharmacology of alendronate sodium. Osteoporos Int. 1993; 3(Suppl 3):513-6.

5. Compston JE. The therapeutic use of bisphosphonates. BMJ. 1994; 309:711-5. [IDIS 337466] [PubMed 7950525]

6. Fleisch H. Bisphosphonates—history and experimental basis. Bone. 1987; 8:S23-8.

7. Patel S, Lyons AR, Hosking DJ. Drugs used in the treatment of metabolic bone disease. Drugs. 1993; 46:594-617. [PubMed 7506648]

8. Chesnut CH III, McClung MR, Ensrud KE et al. Alendronate treatment of the postmenopausal osteoporotic woman: effect of multiple dosages on bone mass and bone remodeling. Am J Med. 1995; 99:144-52. [IDIS 352248] [PubMed 7625419]

9. Schenk R, Eggli P, Fleisch H et al. Quantitative morphometric evaluation of the inhibitory activity of new aminobisphosphonates on bone resorption in the rat. Calcif Tissue Int. 1986; 38:342-9. [PubMed 3089557]

10. Harris ST, Gertz BJ, Genant HK et al. The effect of short term treatment with alendronate on vertebral density and biochemical markers of bone remodeling in early postmenopausal women. J Clin Endocrinol Metab. 1993; 76:1399-1406. [IDIS 316327] [PubMed 8501142]

11. Fleisch H. The use of bisphosphonates in osteoporosis. Br J Clin Pract. 1994; 48:323-6. [IDIS 338642] [PubMed 7848797]

12. Bijvoet OLM, Valkema R, Löwik CWGM et al. The use of bisphosphonate in osteoporosis. In: DeLuca HF, Mazess R, eds. Osteoporosis: physiological basis, assessment, and treatment. New York: Elsevier; 1990:331-8.

13. O’Doherty DP, Gertz BJ, Tindale W et al. Effects of five daily 1 h infusions of alendronate in Paget’s disease of bone. J Bone Miner Res. 1992; 7:81-7. [PubMed 1549961]

14. Krane SM. Paget’s disease of bone. In: Isselbacher KJ, Braunwald E, Wilson JD et al, eds. Harrison’s principles of internal medicine. 13th ed. New York: McGraw Hill Company; 1994:2190-3.

15. Singer FR. Paget’s disease of bone (osteitis deformans). In: Wyngaarden JB, Smith LH, Bennett JC, eds. Cecil’s textbook of medicine. 19th ed. Philadelphia: WB Saunders Company; 1992:1431-3.

16. Rosen CJ, Kessenich CR. Comparative clinical pharmacology and therapeutic use of bisphosphonates in metabolic bone diseases. Drugs. 1996; 51:537-51. [PubMed 8706593]

17. Adami S, Zamberlan N. Adverse effects of bisphosphonates: a comparative review. Drug Safety. 1996; 14:158-70. [PubMed 8934578]

18. Maconi G, Porro GB. Multiple ulcerative esophagitis caused by alendronate. Am J Gastroenterol. 1995; 90:1889-90. [IDIS 354658] [PubMed 7572919]

19. Riggs BL. Osteoporosis. In: Wyngaarden JB, Smith LH Jr, Bennett JC, eds. Cecil textbook of medicine. 19th ed. Philadelphia: WB Saunders Company; 1992:1426-31.

20. De Groen PC, Lubbe DF, Hirsch LJ et al. Esophagitis associated with the use of alendronate. N Engl J Med. 1996; 335:1016-21. [IDIS 372987] [PubMed 8793925]

21. Castell DO. “Pill esophagitis”—the case of alendronate. N Engl J Med. 1996; 335:1058-9. [IDIS 372990] [PubMed 8793934]

22. Liberman UA, Hirsch LJ. Esophagitis and alendronate. N Engl J Med. 1996; 335:1069-70. [IDIS 372999] [PubMed 8801453]

23. Anon. From theMedWatch office: recent safety information on FDA-regulated products—Fosamax tablets (alendronate sodium). FDA Med Bull. 1996; 26(2):4-5.

24. McClung M, Clemmesen B, Daifotis A et al. Alendronate prevents postmenopausal bone loss in women without osteoporosis: a double-blind, randomized, controlled trial. Ann Intern Med. 1998; 128:253-61. [IDIS 401674] [PubMed 9471927]

25. Hosking D, Chilvers CED, Christiansen C et al. Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. N Engl J Med. 1998; 338:485-92. [IDIS 400119] [PubMed 9443925]

26. Wood AJJ. Treatment of postmenopausal osteoporosis. N Engl J Med. 1998; 338:736-46. [IDIS 402219] [PubMed 9494151]

27. Committee on Educational Bulletins of the American College of Obstetricians and Gynecologists. ACOG Educational Bulletin: osteoporosis. Obstet Gynecol. 1998; 91:1-9. [IDIS 403501] [PubMed 9464711]

28. Heaney RP. Bone mass, bone loss, and osteoporosis prophylaxis. Ann Intern Med. 1998; 128:313-4. [IDIS 401677] [PubMed 9471936]

29. Seeman E. Osteoporosis: trials and tribulations. Am J Med. 1997; 103:74-89S. [PubMed 9236490]

30. Liberman UA, Weiss SR, Bröli J et al. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. N Engl J Med. 1995; 333:1437-43. [IDIS 357030] [PubMed 7477143]

31. Tucci JR, Tonino RP, Emkey RD et al. Effect of three years of oral alendronate treatment in postmenopausal women with osteoporosis. Am J Med. 1996; 101:488-501. [IDIS 377583] [PubMed 8948272]

32. Adami S, Passeri M, Ortolani S et al. Effects of oral alendronate and intranasal salmon calcitonin on bone mass and biochemical markers of bone turnover in postmenopausal women with osteoporosis. Bone. 1995; 17:383-90. [PubMed 8573412]

33. Devogelaer JP, Broll H, Correa-Rotter R et al. Oral alendronate induces progressive increases in bone mass of the spine, hip, and total body over 3 years in postmenopausal women with osteoporosis. Bone. 1996; 18:141-50. [PubMed 8833208]

34. Karpf DB, Shapiro DR, Seeman E et al. Prevention of nonvertebral fractures by alendronate: a meta-analysis. JAMA. 1997; 277: 1159-64. [IDIS 382850] [PubMed 9087473]

35. Bone HG, Downs RW Jr, Tucci JR et al. for the Alendroante Elderly Osteoporosis Study Centers. Dose-response relationships for alendronate treatment in osteoporotic elderly women. J Clin Endocrinol Metab. 1997; 82:265-74. [IDIS 377943] [PubMed 8989272]

36. Black DM, Cummings SR, Karpf DB et al. for the Fracture Intervention Trial Research Group. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet. 1996; 348:1535-41. [IDIS 377967] [PubMed 8950879]

37. Merck, West Point, PA: Personal communication.

38. Castelo-Branco C. Management of osteoporosis: an overview. Drugs Aging. 1998; 12(Suppl 1):25-32. [PubMed 9673863]

39. Jeal W, Barradell LB, McTavish D. Alendronate: a review of its pharmacological properties and therapeutic efficacy in postmenopausal osteoporosis. Drugs. 1997; 53:415-34. [PubMed 9074843]

40. Maricic M. Early prevention vs late treatment for osteoporosis. Arch Intern Med. 1997; 157:2545-6. [IDIS 397757] [PubMed 9531221]

41. National Osteoporosis Foundation. Physician’s guide to prevention and treatment of osteoporosis. Washington, DC; 1998.

42. Cummings SR, Black DM, Thompson DE et al. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures. JAMA. 1998; 280:2077-82. [IDIS 416392] [PubMed 9875874]

43. Health Care Financing Administr

Nephplex Rx

Pronunciation: VYE-ta-min B/VYE-ta-min C/BYE-oh-tin/FOE-lik AS-id/zink
Generic Name: Vitamin B Complex/Vitamin C/Biotin/Folic Acid/Zinc
Brand Name: Examples include Ivites Rx and Nephplex Rx

Nephplex Rx is used for:

Treating or preventing a lack of certain vitamins, folic acid, or zinc. It may also be used for other conditions as determined by your doctor.

Nephplex Rx is a vitamin and folic acid combination. It works by providing vitamins and folic acid to the body to help meet nutritional requirements.

Do NOT use Nephplex Rx if:

• you are allergic to any ingredient in Nephplex Rx

Contact your doctor or health care provider right away if any of these apply to you.

Before using Nephplex Rx:

Some medical conditions may interact with Nephplex Rx. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances (including soy)


• if you have anemia (eg, pernicious anemia)

Some MEDICINES MAY INTERACT with Nephplex Rx. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Fluorouracil because the risk of its side effects may be increased by Nephplex Rx


• Hydantoins (eg, phenytoin) because their effectiveness may be decreased by Nephplex Rx

This may not be a complete list of all interactions that may occur. Ask your health care provider if Nephplex Rx may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Nephplex Rx:

Use Nephplex Rx as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Nephplex Rx by mouth with or without food. If stomach upset occurs, take with food to reduce stomach irritation.


• If you are also taking eltrombopag, a quinolone antibiotic (eg, levofloxacin), or a tetracycline antibiotic (eg, doxycycline), ask your doctor how you should take it with Nephplex Rx.


• If you miss a dose of Nephplex Rx, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Nephplex Rx.

Important safety information:

• Do not take large doses of vitamins (megadoses or megavitamin therapy) unless directed by your doctor.


• Nephplex Rx contains pyridoxine (vitamin B₆) and folic acid. Before you start any medicine, check the label to see if it has pyridoxine or folic acid in it too. If it does or if you are not sure, check with your doctor or pharmacist.


• This product may contain tartrazine dye (FD & C Yellow No. 5). This may cause an allergic reaction in some patients. The risk may be higher if you are allergic to aspirin. If you have ever had an allergic reaction to tartrazine, ask your pharmacist if your product has tartrazine in it.


• Nephplex Rx may interfere with certain lab tests. Be sure your doctor and lab personnel know you are taking Nephplex Rx.


• PREGNANCY and BREAST-FEEDING: If you plan on becoming pregnant, contact your doctor. You will need to discuss the benefits and risks of using Nephplex Rx while you are pregnant. It is not known if Nephplex Rx is found in breast milk. If you are or will be breast-feeding while you are using Nephplex Rx, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Nephplex Rx:

All medicines may cause side effects, but many people have no, or minor, side effects. No COMMON side effects have been reported with Nephplex Rx. Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); decreased coordination; decreased sensation of touch, temperature, or vibration; numbness or tingling of the skin.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Nephplex Rx side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include confusion; decreased coordination; mental or mood changes; numbness or tingling of the hands or feet.

Proper storage of Nephplex Rx:

Store Nephplex Rx at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Nephplex Rx out of the reach of children and away from pets.

General information:

• If you have any questions about Nephplex Rx, please talk with your doctor, pharmacist, or other health care provider.


• Nephplex Rx is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Nephplex Rx. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Nephplex Rx resources

• Nephplex Rx Side Effects (in more detail)
• Nephplex Rx Use in Pregnancy & Breastfeeding
• Nephplex Rx Drug Interactions
• Nephplex Rx Support Group
• 0 Reviews for Nephplex Rx - Add your own review/rating

• multivitamin Concise Consumer Information (Cerner Multum)


• Folplex Prescribing Information (FDA)


• Foltabs 800 Prescribing Information (FDA)


• Infuvite Pediatric Prescribing Information (FDA)


• Nephrocaps Prescribing Information (FDA)


• Nephrocaps


• Renal Caps Prescribing Information (FDA)


• Vitamin A Monograph (AHFS DI)

Compare Nephplex Rx with other medications

• Dietary Supplementation

Glyceryl Trinitrate 1mg / ml solution for infusion

1. Name Of The Medicinal Product

Glyceryl Trinitrate 1 mg/ml solution for infusion

2. Qualitative And Quantitative Composition

1 ml solution contains 1 mg glyceryl trinitrate.

Amount of active substance per pack size:

Total Volume	Total GTN Content	Container
5ml	5mg	ampoule
10ml	10mg	ampoule
25ml	25mg	ampoule
50ml	50mg	vial

For excipients, see 6.1.

3. Pharmaceutical Form

Solution for infusion

The product is a clear and colourless solution.

4. Clinical Particulars

4.1 Therapeutic Indications

The following indications exist for Glyceryl Trinitrate:

- Unresponsive congestive heart failure, including that secondary to acute myocardial infarction; acute left-sided heart failure and acute myocardial infarction,

- Refractory unstable angina pectoris and coronary insufficiency, including Prinzmetal's angina,

- Control of hypertensive episodes and/or myocardial ischaemia during and after cardiac surgery,

- Induction of controlled hypotension for surgery.

4.2 Posology And Method Of Administration

For intravenous use. Glyceryl Trinitrate should be administered by means of a micro-drip set infusion pump or similar device which permits maintenance of constant infusion rate.

For instructions on dilution of the product before administration, see section 6.6.

Adults and the elderly - the dose should be titrated against the individual clinical response.

Unresponsive congestive heart failure, acute myocardial infarction and left-sided heart failure. The normal dose range is 10-100 micrograms / minute administered as a continuous intravenous infusion with frequent monitoring of blood pressure and heart rate. The infusion should be started at the lower rate and increased cautiously until the desired clinical response is achieved. Other haemodynamic measurements are extremely important in monitoring response to the drug: These may include pulmonary capillary wedge pressure, cardiac output and precordial electrocardiogram depending on the clinical picture.

Refractory unstable angina pectoris. An initial infusion rate of 10-15 micrograms / minute is recommended; this may be increased cautiously in increments of 5-10 micrograms until either relief of angina is achieved, headache prevents further increase in dose, or the mean arterial pressure falls by more than 20 mm Hg.

Use in surgery. An initial infusion rate of 25 micrograms / minute is recommended; this should be increased gradually until the desired systolic arterial pressure is attained. The usual dose is 25-200 micrograms / minute.

Children – Glyceryl Trinitrate 1 mg/ml solution for infusion is not recommended for use in children.

4.3 Contraindications

Glyceryl Trinitrate should not be used in the following cases: Known hypersensitivity to nitrates, severe anaemia, severe cerebral haemorrhage, head trauma, uncorrected hypovolaemia and hypotensive shock, arterial hypoxaemia and angina caused by hypertrophic obstructive cardiomyopathy, constrictive pericarditis, pericardial tamponade, toxic pulmonary oedema. Sildenafil potentiates the hypotensive effects of nitrates and its co-administration with Glyceryl Trinitrate is contraindicated.

Glyceryl Trinitrate should be administered with caution and under continuous monitoring to patients with acute left-sided heart failure or acute myocardial infarction and only when the systolic blood pressure exceeds 90 mm Hg.

4.4 Special Warnings And Precautions For Use

Caution should be exercised in patients with severe liver or renal disease, hypothermia, hypothyroidism.

Glyceryl Trinitrate should not be given by bolus injection.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Glyceryl trinitrate may potentiate the action of other hypotensive drugs, and the hypotensive and anticholinergic effects of tricyclic antidepressants; it may also slow the metabolism of morphine-like analgesics.

The hypotensive effects of nitrates are potentiated by concurrent administration of sildenafil. A severe and possibly dangerous fall in blood pressure may occur. This can result in collapse, unconsciousness and may be fatal. Such use is therefore contraindicated (section 4.3).

4.6 Pregnancy And Lactation

This product should not be used in pregnancy or in women who are breast feeding infants unless considered essential by the physician.

4.7 Effects On Ability To Drive And Use Machines

Not applicable, because the product is used in hospitalised patients.

4.8 Undesirable Effects

Frequencies of the adverse reactions are listed according to the following convention:

Very common (

Common (

Uncommon (

Rare (

Very rare (< 1/10000),

Not known (cannot be estimated from the available data).

Nervous system disorders:	Very Common: Headache*
Cardiac disorders:	Common: Paradoxical Bradycardia Uncommon: Tachycardia*
Vascular disorders:	Very common: Hypotension* Common: Dizziness*
Gastrointestinal disorders:	Common: Nausea Not known: Retrosternal discomfort
General disorders and administration site conditions:	Not known: Diaphoresis, Flushing*, Restlessness, Abdominal pain

*particularly if the infusion is administered too rapidly.

These symptoms should be readily reversible on reducing the rate of infusion or, if necessary, discontinuing treatment.

4.9 Overdose

Signs and symptoms: Vomiting, restlessness, hypotension, syncope, cyanosis, coldness of the skin, impairment of respiration, bradycardia, psychosis and methaemoglobinaemia may occur.

Treatment: The symptoms may be readily reversed by discontinuing treatment; if hypotension persists, raising the foot of the bed and the use of vasoconstrictors such as intravenous methoxamine or phenylephrine are recommended. Methaemoglobinaemia should be treated by intravenous methylene blue. Oxygen and assisted respiration may be required.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

ATC-Code: C01DA02 Organic nitrates

Glyceryl trinitrate exerts a spasmolytic action on smooth muscle, particularly in the vascular system. This action is more marked on the venous capacitance vessels than the arterial vessels; the predominant increase in venous capacitance results in marked diminution of both the left ventricular filling pressure and volume (preload). The moderate dilation of the arteriolar resistance vessels results in a reduction in afterload. These haemodynamic changes (reductions) in preload and afterload lower the myocardial oxygen demand. In addition, by direct action and through the reduction of myocardial wall tension glyceryl trinitrate also lowers the resistance to flow in the coronary collateral channels and allows re-distribution of blood flow to ischaemic areas of the myocardium.

Administration of glyceryl trinitrate by intravenous infusion to patients with congestive heart failure results in a marked improvement in haemodynamics, reduction of elevated left ventricular filling pressure and systolic wall tension, and an increase in the depressed cardiac output. It reduces the imbalance that exists between myocardial oxygen demand and delivery, thereby diminishing myocardial ischaemia and controlling ischaemia-induced ventricular arrhythmias.

Glyceryl trinitrate relaxes smooth muscles cells in other organs to some extent. The cellular molecular mechanism of action is a synthesis of nitric oxide and cyclic guanosyl monophosphate which acts as a mediator for muscle relaxation.

5.2 Pharmacokinetic Properties

After intravenous administration, glyceryl trinitrate is widely distributed in the body with an estimated apparent volume of distribution of approximately 200 litres. It is strongly bound to erythrocytes and vessel walls; the plasma protein binding is approx. 60%. The therapeutic plasma concentration range is 0.1 to 3 ng/ml (up to 5 ng/ml).

Glyceryl trinitrate is rapidly metabolised to dinitrate and mononitrate and further metabolised by glucuronidation in the liver, showing a marked first-pass effect.

Spontaneous hydrolysis occurs in plasma. The estimated plasma half-life of glyceryl trinitrate is 1 to 4 minutes. The rapid disappearance from plasma is consistent with the high systemic clearance values (up to 3270 litres per hour). The less active metabolites resulting from biotransformation can be recovered from the urine within 24 hours.

5.3 Preclinical Safety Data

The acute toxicity has been reported for rats after intravenous (LD₅₀ 17-41 mg/kg body weight), as well as in dogs after intravenous administration (LD₅₀ 19-24 mg/kg body weight). Autopsy did not reveal any pathological findings.

Subacute studies in rats at doses of 2.5, 5.0 and 10.0 mg/kg per day, and in dogs at doses of 1.0 and 3.0 mg/kg per day elicited only minimal reactions. In rats, suppression of body weight gain and food consumption occurred among treated and vehicle-control animals. Mild tissue irritation at injection sites was noted in treated and vehicle-control groups. There were no clearly drug-related clinical or pathological findings in dogs. Further results of studies on repeated-dose toxicity in different species revealed no indication of drug-specific clinically relevant toxicity.

Glyceryl trinitrate is insufficiently tested for a potential mutagenic action. There are no adequate state-of-the-art long-term studies on a possible tumourigenic action of glyceryl trinitrate.

There is inadequate experience with glyceryl trinitrate during human pregnancy, particularly during the first trimester. Sufficient evidence is available from animal studies with intravenous, intraperitoneal and topical administration. Studies on fertility and embryotoxicity did not result in any toxic effect on the embryo or on reproductive performance. Any indication of a teratogenic potential of glyceryl trinitrate was not found. Doses in excess of 1 mg/kg/day (i.p.) or 28 mg/kg/day (topical) reduced the birth weight in rats. There are no investigations on the passage of glyceryl trinitrate into breast milk.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Water for injections

Glucose monohydrate

Hydrochloric acid

6.2 Incompatibilities

Glyceryl Trinitrate is not compatible with polyvinylchloride (PVC) and severe losses of glyceryl trinitrate (up to 50%) may occur if polyvinylchloride is used, resulting in a reduction of delivered dose and efficacy. Contact of the solution with polyvinylchloride bags should be avoided.

The product is compatible with glass infusion sets and with rigid infusion packs made of polyethylene; it may also be infused slowly using a syringe pump with a glass or plastic syringe.

6.3 Shelf Life

Unopened ampoules: 3 years

Unopened vials: 2 years

Opened ampoules or vials:

The product should be used immediately after opening the container.

Any unused solution from opened containers should be discarded.

Prepared infusion solutions:

Chemical and physical in-use stability has been demonstrated in glucose solution 5 % and sodium chloride solution 0.9 % for 24 hours at room temperature.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.

6.4 Special Precautions For Storage

Keep the container in the outer carton.

Do not store above 25°C.

6.5 Nature And Contents Of Container

5 ml, 10 ml or 25 ml ampoules, made of colourless glass, type I.

50 ml vial, made of colourless glass, type I, rubber stopper.

Box of 10 ampoules with 5 ml

Box of 10 ampoules with 10 ml

Box of 10 ampoules with 25 ml

Box of 1 vial with 50 ml

Box of 10 vials with 50 ml

Box of 25 vials with 50 ml

Not all pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

Glyceryl Trinitrate need not be diluted before use but can be diluted by 1:10 up to 1:40 with 5 % glucose solution, 5 % glucose solution and 0.9 % sodium chloride solution, or with 0.9 % sodium chloride solution.

The solution, whether or not diluted, should be infused slowly and not given by bolus injection. To ensure a constant infusion rate of glyceryl trinitrate it is recommended that Glyceryl Trinitrate be administered by means of a syringe pump or polyethylene infusion bag with a counter, or with a glass or rigid polyethylene syringe and polyethylene tubing. Systems made of polyvinyl chloride (PVC) may absorb up to 50% of the glyceryl trinitrate from the solution.

Vials of 50 ml Glyceryl Trinitrate are for single use only and should not be regarded as multi-dose containers.

7. Marketing Authorisation Holder

hameln pharma plus gmbh

Langes Feld 13

31789 Hameln

Germany

8. Marketing Authorisation Number(S)

PL 25215/0011

9. Date Of First Authorisation/Renewal Of The Authorisation

04/09/2008

10. Date Of Revision Of The Text

04/06/2009

Prescription-only medicine

Ziprasidone

Class: Atypical Antipsychotics
VA Class: CN709
Chemical Name: 5-[2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]ethyl]-6-chloro-1,3-dihydro-2H-indol-2-one monohydrochloride monohydrate
Molecular Formula: C₂₁H₂₁ClN₄OS•HCl•H₂OC₂₁H₂₁ClN₄OS•CH₄O₃S•3H₂O
CAS Number: 138982-67-9
Brands: Geodon

Special Alerts:

[Posted 02/22/2011] ISSUE: FDA notified healthcare professionals that the Pregnancy section of drug labels for the entire class of antipsychotic drugs has been updated. The new drug labels now contain more and consistent information about the potential risk for abnormal muscle movements (extrapyramidal signs or EPS) and withdrawal symptoms in newborns whose mothers were treated with these drugs during the third trimester of pregnancy.

The symptoms of EPS and withdrawal in newborns may include agitation, abnormally increased or decreased muscle tone, tremor, sleepiness, severe difficulty breathing, and difficulty in feeding. In some newborns, the symptoms subside within hours or days and do not require specific treatment; other newborns may require longer hospital stays.

BACKGROUND: Antipsychotic drugs are used to treat symptoms of psychiatric disorders such as schizophrenia and bipolar disorder.

RECOMMENDATION: Healthcare professionals should be aware of the effects of antipsychotic medications on newborns when the medications are used during pregnancy. Patients should not stop taking these medications if they become pregnant without talking to their healthcare professional, as abruptly stopping antipsychotic medications can cause significant complications for treatment. For more information visit the FDA website at: and .

• Increased Mortality in Geriatric Patients


• 
  

  Substantially higher mortality rate (4.5%) in geriatric patients with dementia-related psychosis† receiving atypical antipsychotic agents (e.g., aripiprazole, olanzapine, quetiapine, risperidone) compared with those receiving placebo (2.6%).^{1 68}

  
  


• 
  

  Most fatalities resulted from cardiac-related events (e.g., heart failure, sudden death) or infections (mostly pneumonia).^{1 68}

  
  


• 
  

  Atypical antipsychotics are not approved for the treatment of dementia-related psychosis.^{1 68} (See Increased Mortality in Geriatric Patients with Dementia-related Psychosis under Cautions.)

  
  

Introduction

Atypical or second-generation antipsychotic agent.^{1 4 10 11 29}

Uses for Ziprasidone

Schizophrenia

Symptomatic management of schizophrenia.¹

Should be reserved for patients whose disease fails to respond adequately to appropriate courses of other antipsychotic agents because of a greater capacity to prolong the QT/QT_c-interval compared with that of several other antipsychotic agents.¹ (See Prolongation of QT Interval under Cautions)

IM injection used for rapid control of behaviors that interfere with diagnosis and care (e.g., threatening behaviors, escalating or urgently distressing behavior, self-exhausting behavior).¹

Bipolar Disorder

Treatment of acute manic and mixed epsiodes (with or without psychotic features) associated with bipolar 1 disorder.^{1 73 74}

Ziprasidone Dosage and Administration

Administration

Administer orally or by IM injection.¹

Concomitant use of oral and IM ziprasidone not recommended by manufacturer.¹

Oral Administration

Administer orally twice daily with food.¹

IM Administration

Vials are for single use only.¹

Reconstitution

Reconstitute vial containing 20 mg with 1.2 mL of sterile water for injection to provide a solution containing 20 mg/mL.¹ Do not use other solutions to reconstitute the injection, and do not admix with other drugs.¹ Shake vigorously to ensure complete dissolution.¹

Observe strict aseptic technique since the drug contains no preservative.¹ Discard unused portions.¹

Dosage

Available as ziprasidone hydrochloride or ziprasidone mesylate; oral dosage expressed in terms of hydrochloride monohydrate and IM dosage expressed in terms of ziprasidone.^{1 12}

Adults

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Schizophrenia

Oral

Initially, 20 mg twice daily.¹

Dosage may be increased after a minimum of 2 days.^{1 12} Observe patients for several weeks prior to upward titrations of dosage to ensure use of the lowest effective dosage.¹

In patients responding to ziprasidone therapy, continue the drug as long as clinically necessary and tolerated, but at lowest possible effective dosage;¹² periodically reassess need for continued therapy.¹ Efficacy maintained for up to 52 weeks in clinical trials, but optimum duration of therapy currently is not known.¹

Acute Agitation in Schizophrenia

IM

Initially, 10–20 mg given as a single dose.¹

Repeat doses of 10 mg every 2 hours or 20 mg every 4 hours, up to a maximum cumulative dosage of 40 mg daily.¹

Oral therapy should replace IM therapy as soon as possible; safety and efficacy of administering ziprasidone IM injection for longer than 3 consecutive days not evaluated.¹

Bipolar Disorder

Oral

Initially, 40 mg twice daily on day 1.¹ Increase dosage to 60 or 80 mg twice daily on the second day.¹

Subsequent dosage adjustments based on efficacy and tolerability may be made within a dosage range of 40–80 mg twice daily.¹

Efficacy for long-term use (i.e., >3 weeks) or for prophylactic use in patients with bipolar disorder not systematically evaluated.¹ If used for extended periods, periodically reevaluate the long-term risks and benefits for the individual patient.¹

Prescribing Limits

Adults

Schizophrenia

Oral

Maximum 80 mg twice daily.^{1 12}

Acute Agitation

IM

Maximum cumulative dosage of 40 mg daily.

Bipolar Disorder

Oral

Maximum 80 mg twice daily.¹

Cautions for Ziprasidone

Contraindications

• 
  

  Known history of QT interval prolongation (including congenital long QT syndrome), recent AMI, or uncompensated heart failure.¹ (See Prolongation of QT Interval under Cautions.)

  
  


• 
  

  Concomitant therapy with other drugs that prolong the QT interval (e.g., class Ia and III antiarrhythmics, arsenic trioxide, chlorpromazine, dofetilide, dolasetron mesylate, droperidol, gatifloxacin, halofantrine, levomethadyl acetate, mefloquine, mesoridazine, moxifloxacin, pentamidine, pimozide, probucol, quinidine, sotalol, sparfloxacin, tacrolimus, thioridazine).¹ Ziprasidone also is contraindicated in patients receiving drugs shown to cause QT prolongation as an effect and for which this effect is described in the full prescribing information as a contraindication or a boxed or bolded warning.¹

  
  


• 
  

  Known hypersensitivity to ziprasidone.¹

  
  

Warnings/Precautions

Warnings

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Increased Mortality in Geriatric Patients with Dementia-related Psychosis

Possible increased risk of death with use of atypical antipsychotics in geriatric patients with dementia-related psychosis.^{1 68} (See Boxed Warning and see Geriatric Use under Cautions.)

Atypical antipsychotics are not approved for the treatment of dementia-related psychosis.^{1 68}

Prolongation of QT Interval

Greater capacity to prolong the QT/QT_c interval compared with that of several other antipsychotic agents.¹

Experience is too limited to rule out the possibility that ziprasidone may be associated with a greater risk of ventricular arrhythmias (e.g., torsades de pointes) and/or sudden death than other antipsychotic agents.¹

Patients at particular risk of torsades de pointes include those with bradycardia, hypokalemia, or hypomagnesemia, those receiving concomitant therapy with other drugs that prolong the QT_c interval, and those with congenital prolongation of QT_c interval.¹ (See Contraindications under Cautions.) Avoid ziprasidone therapy in patients with history of cardiac arrhythmias.¹

Determine baseline serum potassium and magnesium concentrations in patients at risk for substantial electrolyte disturbances, particularly those receiving concomitant diuretic therapy.¹ Correct hypokalemia or hypomagnesemia prior to initiating ziprasidone.¹

Clinical and ECG monitoring of cardiac function, including appropriate ambulatory ECG monitoring (e.g., Holter monitoring), is recommended during ziprasidone therapy in patients with symptoms that could indicate torsades de pointes (e.g., dizziness, palpitations, syncope).¹

Discontinue ziprasidone if the QT_c interval exceeds 500 msec.¹

Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome (NMS), a potentially fatal syndrome requiring immediate discontinuance of the drug and intensive symptomatic treatment, may occur in patients receiving antipsychotic agents.^{1 12}

Tardive Dyskinesia

Tardive dyskinesia, a syndrome of potentially irreversible, involuntary, dyskinetic movements, has been reported.¹ Consider discontinuance of ziprasidone.¹

Hyperglycemia and Diabetes Mellitus

Severe hyperglycemia, sometimes associated with ketoacidosis, hyperosmolar coma, or death, reported in patients receiving atypical antipsychotic agents.^{1 13 14 15 16 17 18 19 20 21 22 23 24 25 26 40 41 42 43 47} Closely monitor patients with preexisting diabetes mellitus for worsening of glucose control, and perform fasting glucose tests at baseline and periodically for patients with risk factors for diabetes (e.g., obesity, family history of diabetes).^{1 13 14 16 17 18 19 20 21 22 23 24 25} If manifestations of hyperglycemia occur, test for diabetes mellitus.^{1 13 14 16 17 18 19 20 21 22 23 24 25}

Sensitivity Reactions

Rash

Rash and/or urticaria, possibly related to dose and/or duration of therapy, reported.¹ Adjunctive treatment with antihistamines or steroids and/or drug discontinuance may be required.¹ Discontinue ziprasidone if alternative etiology of rash cannot be identified.¹

General Precautions

Cardiovascular Effects

Orthostatic hypotension reported, particularly during initial dosage titration period.¹ Use with caution in patients with known cardiovascular or cerebrovascular disease and/or conditions that would predispose patients to hypotension (e.g., dehydration, hypovolemia, concomitant antihypertensive therapy).¹

Nervous System Effects

Possible risk of seizures;¹ use with caution in patients with a history of seizures or with conditions known to lower the seizure threshold (e.g., dementia of the Alzheimer’s type, geriatric patients).¹

Disruption of ability to reduce core body temperature possible; use caution in patients exposed to conditions that may contribute to an elevation in core body temperature (e.g., dehydration, extreme heat, strenuous exercise, concomitant use of anticholinergic agents).¹

Somnolence reported.¹ Potential impairment of judgment, thinking, or motor skills.¹

GI Effects

Esophageal dysmotility and aspiration possible; use with caution in patients at risk for aspiration pneumonia (e.g., geriatric patients, those with advanced Alzheimer’s dementia).¹ (See Boxed Warning and see Increased Mortality in Geriatric Patients with Dementia-related Psychosis under Cautions.)

Suicide

Attendant risk with psychotic illnesses; closely supervise high-risk patients.¹ Prescribe in the smallest quantity consistent with good patient management to reduce the risk of overdosage.¹

Sexual Dysfunction

Priapism possible.¹

Endocrine Effects

Elevated prolactin concentrations possible.⁷

Metabolic Effects

Weight gain possible.^{1 7} May cause less weight gain than clozapine, olanzapine, quetiapine, or risperidone.^{4 10 11 12}

Specific Populations

Pregnancy

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Category C.¹

Lactation

Not known whether ziprasidone is distributed into milk.¹ Women receiving ziprasidone should not breast-feed.¹

Pediatric Use

Safety and efficacy not established in children <18 years of age.¹

Geriatric Use

No substantial differences in safety of oral ziprasidone relative to younger adults.¹

Lower initial dosages, slower titration, and careful monitoring during the initial dosing period may be advisable in some geriatric patients.¹

IM ziprasidone mesylate not systematically evaluated in geriatric patients.¹

Possible increased risk of death in geriatric patients with dementia-related psychosis.^{1 68} Substantial (1.6- to 1.7-fold) increase in mortality rate reported in geriatric patients with dementia who received atypical antipsychotic agents (e.g., aripiprazole, olanzapine, quetiapine, risperidone) for treatment of behavioral disorders; most fatalities resulted from cardiac-related events (e.g., heart failure, sudden death) or infections (mostly pneumonia).^{1 68}

Atypical antipsychotics are not approved for the treatment of dementia-related psychosis.^{1 68} (See Boxed Warning and see Increased Mortality in Geriatric Patients with Dementia-related Psychosis under Cautions.)

Renal Impairment

Commercially available ziprasidone mesylate injections contain sulfobutylether β-cyclodextrin sodium, an excipient that is cleared by renal filtration; use with caution.¹

Common Adverse Effects

Oral therapy for schizophrenia: somnolence, respiratory tract infection.¹

Oral therapy for bipolar mania: somnolence, extrapyramidal symptoms, dizziness, akathisia, abnormal vision, asthenia, vomiting.^{1 73 74}

IM therapy for acute agitation in schizophrenia: somnolence, headache, nausea.¹

Interactions for Ziprasidone

Ziprasidone is metabolized by the CYP3A4 isoenzyme; CYP1A2 also may contribute but to a much lesser extent.¹ Little inhibitory effect on CYP isoenzymes 1A2, 2C9, 2C19, 2D6, or 3A4; pharmacokinetic interaction unlikely with drugs metabolized by these isoenzymes.¹

Drugs Affecting Hepatic Microsomal Enzymes

Potential pharmacokinetic interactions (altered metabolism) with inhibitors or inducers of CYP3A4.¹

Pharmacokinetic interaction with inhibitors or inducers of CYP1A2, CYP2C9, CYP2C19, or CYP2D6 are unlikely.¹

Drugs That Prolong QT Interval

Potential pharmacologic interaction (additive effect on QT interval prolongation; concomitant use contraindicated) when used with drugs that prolong the QT_c interval.¹ Ziprasidone also is contraindicated in patients receiving drugs shown to cause QT prolongation as an effect and for which this effect is described in the full prescribing information as a contraindication or a boxed or bolded warning.¹ (See Contraindications and Prolongation of QT Interval under Cautions.)

Specific Drugs

Drug	Interaction	Comments
Antacids	No effects on ziprasidone pharmacokinetics1
Antiarrhythmics (class Ia and III)	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Arsenic trioxide	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Benztropine	Pharmacokinetic interaction unlikely1
Carbamazepine	Increased ziprasidone metabolism1
Chlorpromazine	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Cimetidine	No change observed in ziprasidone pharmacokinetics1
CNS agents	Additive sedative effects12
Dextromethorphan	No change observed in dextromethorphan metabolism1
Dofetilide	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Dolasetron mesylate	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Dopamine agonists	Antagonistic effects1
Droperidol	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Gatifloxacin	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Halofantrine	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Hypotensive agents	Additive hypotensive effects1	Use with caution1
Ketoconazole	Increased plasma ziprasidone concentrations1
Levodopa	Antagonistic effects1
Levomethadyl acetate	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Lithium	No change observed in lithium clearance1
Lorazepam	Pharmacokinetic interaction unlikely1
Mefloquine	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Mesoridazine	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Moxifloxacin	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Oral contraceptives	No change observed in estradiol or levonorgestrel pharmacokinetics1
Pentamidine	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Pimozide	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Probucol	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Protein-bound drugs (e.g., propranolol, warfarin)	Pharmacokinetic interaction unlikely1
Quinidine	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Sotalol	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Sparfloxacin	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Tacrolimus	Increased risk of QT interval prolongation1	Concomitant use contraindicated1
Thioridazine	Increased risk of QT interval prolongation1	Concomitant use contraindicated1

Ziprasidone Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability is approximately 60% following a 20 mg oral dose under fed conditions.¹

Peak plasma concentrations occur 6–8 hours after oral administration or about 1 hour after IM injection.¹

Food

Food increases the absorption up to twofold.¹

Distribution

Extent

Not known whether the drug is distributed into milk in humans.¹

Plasma Protein Binding

>99% bound to plasma proteins, principally to albumin and α₁-acid glycoprotein.¹

Elimination

Metabolism

Extensively metabolized in the liver principally via reduction by aldehyde oxidase; about one-third of metabolic clearance is mediated by CYP isoenzymes, principally CYP3A4.¹

Elimination Route

Approximately 20% of a dose is excreted in the urine and about 66% in feces, principally as metabolites.¹ Not removed by hemodialysis.¹

Half-life

Mean terminal half-life following oral administration is about 7 hours;¹ following IM administration, the half-life is 2–5 hours.¹

Special Populations

In patients with clinically important (Child-Pugh class A or B) cirrhosis, half-life increased by 2.3 hours compared with that of patients in the control group.¹

Stability

Storage

Oral

Capsules

15–30°C.¹

Parenteral

Powder for Injection

15–30°C.¹

Following reconstitution, store at 15–30°C protected from light for up to 24 hours or at 2–8°C for up to 7 days.¹

ActionsActions

• 
  

  Exact mechanism of antipsychotic action has not been fully elucidated; may involve antagonism of central type 2 serotonergic (5-HT₂) receptors and central dopamine D₂ receptors.^{1 8 9}

  
  


• 
  

  Precise mechanism of antimanic action has not been fully elucidated.¹

  
  


• 
  

  Antagonism of other receptors (e.g., histamine H₁ receptors, α₁-adrenergic receptors) may contribute to other therapeutic and adverse effects (e.g., orthostatic hypotension, somnolence).¹

  
  

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

• 
  

  Importance of taking medication exactly as prescribed by the clinician.¹

  
  


• 
  

  Importance of avoiding driving, operating machinery, or performing hazardous tasks until gain experience with the drug’s effects.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription or OTC drugs, dietary supplements, and herbal products, as well as any concomitant illnesses (e.g., diabetes mellitus, seizures, dementia).¹

  
  


• 
  

  Importance of avoiding alcohol during ziprasidone therapy.¹

  
  


• 
  

  Importance of avoiding overheating or dehydration.¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

  
  


• 
  

  Importance of informing patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

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

Ziprasidone Hydrochloride

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	20 mg	Geodon	Pfizer
		40 mg	Geodon	Pfizer
		60 mg	Geodon	Pfizer
		80 mg	Geodon	Pfizer

Ziprasidone Mesylate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection, for IM use only	20 mg (of ziprasidone) per mL	Geodon (with sulfobutylether β-cyclodextrin sodium 294 mg/mL)	Pfizer

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 04/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Geodon 20MG Capsules (PFIZER U.S.): 60/$478.01 or 180/$1402.96

Geodon 40MG Capsules (PFIZER U.S.): 60/$482.99 or 180/$1407.94

Geodon 60MG Capsules (PFIZER U.S.): 60/$574.97 or 180/$1687.92

Geodon 80MG Capsules (PFIZER U.S.): 60/$574.97 or 180/$1687.92

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 March 15, 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

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3. Keck P, Buffenstein A, Ferguson J et al. Ziprasidone 40 and 120 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 4-week placebo-controlled trial. Psychopharmacology1998; 140:173-84.

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8. Lilly. Zyprexa (olanzapine tablets and orally disintegrating tablets) prescribing information. Indianapolis, IN; 2001 Feb.

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38. Fuller MA, Shermock KM, Secic M et al. Comparative study of the development of diabetes mellitus in patients taking risperidone and olanzapine. Pharmacotherapy. 2002; 23:1037-43.

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41. Ananth J, Johnson KM, Levander EM et al. Diabetic ketoacidosis, neuroleptic malignant syndrome, and myocardial infarction in a patient taking risperidone and lithium carbonate. J Clin Psychiatry. 2004; 65:724. [IDIS 516345] [PubMed 15163265]

42. Torrey EF, Swalwell CI. Fatal olanzapine-induced ketoacidosis. Am J Psychiatry. 2003; 160:2241. [IDIS 516756] [PubMed 14638601]

43. Wehring HJ, Kelly DL, Love RC et al. Deaths from diabetic ketoacidosis after long-term clozapine treatment. Am J Psychiatry. 2003; 160:2241-2. [IDIS 516757] [PubMed 14638600]

44. Koro CE, Fedder DO, L’Italien GJ et al. Assessment of independent effect of olanzapine and risperidone on risk of diabetes among patients with schizophrenia: population based nested case-control study. BMJ. 2002; 325:243. [IDIS 485916] [PubMed 12153919]

45. Citrome LL. Efficacy should drive atypical antipsychotic treatment. BMJ. 2003; 326:283. [IDIS 492968] [PubMed 12561827]

46. Anon. Which atypical antipsychotic for schizophrenia?. Drug Ther Bull. 2004; 42:57-60. [PubMed 15310154]

47. Anon. Atypical antipsychotics and hyperglycaemia. Aust Adv Drug React Bull. 2004; 23:11-2.

48. Sussman N. The implications of weight changes with antipsychotic treatment. J Clin Psychopharmacol. 2003; 23 (Suppl 1):S21-6.

49. Gianfrancesco F, Grogg A, Mahmoud R et al. Differential effects of antipsychotic agents on the risk of development of type 2 diabetes mellitus in patients with mood disorders. Clin Ther. 2003; 25:1150-71. [IDIS 497269] [PubMed 12809963]

50. Bushe C, Leonard B. Association between atypical antipsychotic agents and type 2 diabetes: review of prospective clinical data. Br J Psychiatry Suppl. 2004; 47:S87-93. [PubMed 15056600]

51. Cavazzoni P, Mukhopadhyay N, Carlson C et al. Retrospective analysis of risk factors in patients with treatment-emergent diabetes during clinical trials of antipsychotic medications. Br J Psychiatry Suppl. 2004; 47:s94-101. [PubMed 15056601]

52. Gianfrancesco FD, Grogg AL, Mahmoud RA et al. Differential effects of risperidone, olanzapine, clozapine, and conventional antipsychotics on type 2 diabetes: findings from a large health plan database. J Clin Psychiatry. 2002; 63:920-30. [IDIS 488480] [PubMed 12416602]

53. Etminan M, Streiner DL, Rochon PA. Exploring the association between atypical neuroleptic agents and diabetes mellitus in older adults. Pharmacotherapy. 2003; 23:1411-15. [IDIS 510498] [PubMed 14620387]

54. Leslie DL, Rosenheck RA. Incidence of newly diagnosed diabetes attributable to atypical antipsychotic medications. Am J Psychiatry. 2004; 161:1709-11. [IDIS 522186] [PubMed 15337666]

55. Sernyak MJ, Leslie DL, Alarcon RD et al. Association of diabetes mellitus with use of atypical neuroleptics in the treatment of schizophrenia. Am J Psychiatry. 2002; 159:561-6. [IDIS 494206] [PubMed 11925293]

56. Geller WK, MacFadden W. Diabetes and atypical neuroleptics. Am J Psychiatry. 2003; 160:388. [IDIS 513919] [PubMed 12562601]

57. Gianfrancesco FD. Diabetes and atypical neuroleptics. Am J Psychiatry. 2003; 160:388-9; author reply 389. [IDIS 513920] [PubMed 12562599]

58. Lamberti JS, Crilly JF, Maharaj K. Prevalence of diabetes mellitus among outpatients with severe mental disorders receiving atypical antipsychotic drugs. J Clin Psychiatry. 2004; 65:702-6. [IDIS 516341] [PubMed 15163259]

59. Lee DW, Fowler RB. Olanzapine/risperidone and diabetes risk. J Clin Psychiatry. 2003; 64:847-8; author reply 848. [IDIS 500324] [PubMed 12934988]

60. Reviewer Comments (personal observations).

61. Bristol-Myers Squibb., Princeton, NJ: Personal communication.

62. AstraZeneca. Wayne, PA: Personal communication.

63. Eli Lilly and Company. Indianapolis, IN: Personal communication.

64. Novartis Pharmaceuticals Corporation. East Hanover, NJ: Personal communication.

65. Janssen Pharmaceuticals. Titusville, NJ: Personal communicat