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Friday, 20 July 2012

Naropin 10 mg / ml solution for injection

1. Name Of The Medicinal Product

Naropin^®10 mg/ml solution for injection

2. Qualitative And Quantitative Composition

Naropin^® 10 mg/ml:

1 ml solution for injection contains ropivacaine hydrochloride monohydrate equivalent to 10 mg ropivacaine hydrochloride.

1 ampoule of 10 ml or 20 ml solution for injection contains ropivacaine hydrochloride monohydrate equivalent to 100 mg and 200 mg ropivacaine hydrochloride respectively.

For excipients, see section 6.1.

3. Pharmaceutical Form

Solution for injection for perineural and epidural administration (10–20 ml).

Clear, colourless solution.

4. Clinical Particulars

4.1 Therapeutic Indications

Naropin is indicated for:

1. Surgical anaesthesia

2. Acute pain management

4.2 Posology And Method Of Administration

Naropin should only be used by, or under the supervision of, clinicians experienced in regional anaesthesia.

Posology

Adults and children above 12 years of age:

The following table is a guide to dosage for the more commonly used blocks. The smallest dose required to produce an effective block should be used. The clinician's experience and knowledge of the patient's physical status are of importance when deciding the dose.

	Conc.	Volume	Dose	Onset	Duration
	mg/ml	ml	mg	minutes	hours
Surgical anaesthesia
Lumbar Epidural Administration
Surgery	7.5	15–25	113–188	10–20	3–5
	10	15–20	150–200	10–20	4–6
Caesarean section	7.5	15–20	113–150⁽¹⁾	10–20	3–5
Thoracic Epidural Administration
To establish block for postoperative pain relief	7.5	5–15 (depending on the level of injection)	38–113	10–20	n/a⁽²⁾
Major Nerve Block *
Brachial plexus block	7.5	30–40	225–300⁽³⁾	10–25	6–10
Field Block	7.5	1–30	7.5–225	1–15	2–6
(e.g. minor nerve blocks and infiltration)
Acute pain management
Lumbar Epidural Administration
Bolus	2	10–20	20–40	10–15	0.5–1.5
Intermittent injections (top up) (e.g. labour pain management)	2	10–15 (minimum interval 30 minutes)	20–30
Continuous infusion e.g. labour pain	2	6–10 ml/h	12–20 mg/h	n/a⁽²⁾	n/a⁽²⁾
Postoperative pain management	2	6–14 ml/h	12–28 mg/h	n/a⁽²⁾	n/a⁽²⁾
Thoracic Epidural Administration
Continuous infusion (postoperative pain management)	2	6–14 ml/h	12–28 mg/h	n/a⁽²⁾	n/a⁽²⁾
Field Block
(e.g. minor nerve blocks and infiltration)	2	1–100	2–200	1–5	2–6
Peripheral nerve block (Femoral or interscalene block)
Continuous infusion or intermittent injections (e.g. postoperative pain management)	2	5–10 ml/h	10–20 mg/h	n/a	n/a
The doses in the table are those considered to be necessary to produce a successful block and should be regarded as guidelines for use in adults. Individual variations in onset and duration occur. The figures in the column 'Dose' reflect the expected average dose range needed. Standard textbooks should be consulted for both factors affecting specific block techniques and individual patient requirements.
* With regard to major nerve block, only for brachial plexus block a dose recommendation can be given. For other major nerve blocks lower doses may be required. However, there is presently no experience of specific dose recommendations for other blocks.
(1) Incremental dosing should be applied, the starting dose of about 100 mg (97.5 mg = 13 ml; 105 mg = 14 ml) to be given over 3–5 minutes. Two extra doses, in total an additional 50mg, may be administered as needed. (2) n/a = not applicable (3) The dose for a major nerve block must be adjusted according to site of administration and patient status. Interscalene and supraclavicular brachial plexus blocks may be associated with a higher frequency of serious adverse reactions, regardless of the local anaesthetic used, (see section 4.4. Special warnings and special precautions for use).

In general, surgical anaesthesia (e.g. epidural administration) requires the use of the higher concentrations and doses. The Naropin 10 mg/ml formulation is recommended for epidural anaesthesia in which a complete motor block is essential for surgery. For analgesia (e.g. epidural administration for acute pain management) the lower concentrations and doses are recommended.

Method of administration

Careful aspiration before and during injection is recommended to prevent intravascular injection. When a large dose is to be injected, a test dose of 3–5 ml lidocaine (lignocaine) with adrenaline (epinephrine) (Xylocaine^® 2% with Adrenaline (epinephrine) 1:200,000) is recommended. An inadvertent intravascular injection may be recognised by a temporary increase in heart rate and an accidental intrathecal injection by signs of a spinal block.

Aspiration should be performed prior to and during administration of the main dose, which should be injected slowly or in incremental doses, at a rate of 25–50 mg/min, while closely observing the patient's vital functions and maintaining verbal contact. If toxic symptoms occur, the injection should be stopped immediately.

In epidural block for surgery, single doses of up to 250 mg ropivacaine have been used and well tolerated.

In brachial plexus block a single dose of 300 mg has been used in a limited number of patients and was well tolerated.

When prolonged blocks are used, either through continuous infusion or through repeated bolus administration, the risks of reaching a toxic plasma concentration or inducing local neural injury must be considered. Cumulative doses up to 675 mg ropivacaine for surgery and postoperative analgesia administered over 24 hours were well tolerated in adults, as were postoperative continuous epidural infusions at rates up to 28 mg/hour for 72 hours. In a limited number of patients, higher doses of up to 800 mg/day have been administered with relatively few adverse reactions.

For treatment of postoperative pain, the following technique can be recommended: Unless preoperatively instituted, an epidural block with Naropin 7.5 mg/ml is induced via an epidural catheter. Analgesia is maintained with Naropin 2 mg/ml infusion. Infusion rates of 6–14 ml (12–28 mg) per hour provide adequate analgesia with only slight and non-progressive motor block in most cases of moderate to severe postoperative pain. The maximum duration of epidural block is 3 days. However, close monitoring of analgesic effect should be performed in order to remove the catheter as soon as the pain condition allows it. With this technique a significant reduction in the need for opioids has been observed.

In clinical studies an epidural infusion of Naropin 2 mg/ml alone or mixed with fentanyl 1-4 μg/ml has been given for postoperative pain management for up to 72 hours. The combination of Naropin and fentanyl provided improved pain relief but caused opioid side effects. The combination of Naropin and fentanyl has been investigated only for Naropin 2 mg/ml.

When prolonged peripheral nerve blocks are applied, either through continuous infusion or through repeated injections, the risks of reaching a toxic plasma concentration or inducing local neural injury must be considered. In clinical studies, femoral nerve block was established with 300 mg Naropin 7.5 mg/ml and interscalene block with 225 mg Naropin 7.5 mg/ml, respectively, before surgery. Analgesia was then maintained with Naropin 2 mg/ml. Infusion rates or intermittent injections of 10–20 mg per hour for 48 hours provided adequate analgesia and were well tolerated.

Concentrations above 7.5 mg/ml Naropin have not been documented for Caesarean section.

4.3 Contraindications

Hypersensitivity to ropivacaine or to other local anaesthetics of the amide type.

General contraindications related to epidural anaesthesia, regardless of the local anaesthetic used, should be taken into account.

Intravenous regional anaesthesia.

Obstetric paracervical anaesthesia.

Hypovolaemia.

4.4 Special Warnings And Precautions For Use

Regional anaesthetic procedures should always be performed in a properly equipped and staffed area. Equipment and drugs necessary for monitoring and emergency resuscitation should be immediately available. Patients receiving major blocks should be in an optimal condition and have an intravenous line inserted before the blocking procedure. The clinician responsible should take the necessary precautions to avoid intravascular injection (see section 4.2 Posology and method of administration) and be appropriately trained and familiar with diagnosis and treatment of side effects, systemic toxicity and other complications (see section 4.8 Undesirable effects and 4.9 Overdose) such as inadvertent subarachnoid injection, which may produce a high spinal block with apnoea and hypotension. Convulsions have occurred most often after brachial plexus block and epidural block. This is likely to be the result of either accidental intravascular injection or rapid absorption from the injection site.

Caution is required to prevent injections in inflamed areas.

Cardiovascular

Patients treated with anti-arrhythmic drugs class III (eg, amiodarone) should be under close surveillance and ECG monitoring considered, since cardiac effects may be additive.

There have been rare reports of cardiac arrest during the use of Naropin for epidural anaesthesia or peripheral nerve blockade, especially after unintentional accidental intravascular administration in elderly patients and in patients with concomitant heart disease. In some instances, resuscitation has been difficult. Should cardiac arrest occur, prolonged resuscitative efforts may be required to improve the possibility of a successful outcome.

Head and neck blocks

Certain local anaesthetic procedures, such as injections in the head and neck regions, may be associated with a higher frequency of serious adverse reactions, regardless of the local anaesthetic used.

Major peripheral nerve blocks

Major peripheral nerve blocks may imply the administration of a large volume of local anaesthetic in highly vascularized areas, often close to large vessels where there is an increased risk of intravascular injection and/or rapid systemic absorption, which can lead to high plasma concentrations.

Hypersensitivity

A possible cross–hypersensitivity with other amide–type local anaesthetics should be taken into account.

Hypovolaemia

Patients with hypovolaemia due to any cause can develop sudden and severe hypotension during epidural anaesthesia, regardless of the local anaesthetic used.

Patients in poor general health

Patients in poor general condition due to ageing or other compromising factors such as partial or complete heart conduction block, advanced liver disease or severe renal dysfunction require special attention, although regional anaesthesia is frequently indicated in these patients.

Patients with hepatic and renal impairment

Ropivacaine is metabolised in the liver and should therefore be used with caution in patients with severe liver disease; repeated doses may need to be reduced due to delayed elimination. Normally there is no need to modify the dose in patients with impaired renal function when used for single dose or short-term treatment. Acidosis and reduced plasma protein concentration, frequently seen in patients with chronic renal failure, may increase the risk of systemic toxicity.

Acute porphyria

Naropin^® solution for injection and infusion is possibly porphyrinogenic and should only be prescribed to patients with acute porphyria when no safer alternative is available. Appropriate precautions should be taken in the case of vulnerable patients, according to standard textbooks and/or in consultation with disease area experts.

Excipients with recognised action/effect

This medicinal product contains maximum 3.7 mg sodium per ml. To be taken into consideration by patients on a controlled sodium diet.

Prolonged administration

Prolonged administration of ropivacaine should be avoided in patients concomitantly treated with strong CYP1A2 inhibitors, such as fluvoxamine and enoxacin, see section 4.5.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Naropin should be used with caution in patients receiving other local anaesthetics or agents structurally related to amide-type local anaesthetics, e.g. certain antiarrhythmics, such as lidocaine and mexiletine, since the systemic toxic effects are additive. Simultaneous use of Naropin with general anaesthetics or opioids may potentiate each others (adverse) effects. Specific interaction studies with ropivacaine and anti-arrhythmic drugs class III (e.g. amiodarone) have not been performed, but caution is advised (see also section 4.4 Special warnings and precautions for use).

Cytochrome P450 (CYP) 1A2 is involved in the formation of 3-hydroxy-ropivacaine, the major metabolite. In vivo, the plasma clearance of ropivacaine was reduced by up to 77% during co

In vivo, the plasma clearance of ropivacaine was reduced by 15% during co

In vitro, ropivacaine is a competitive inhibitor of CYP2D6 but does not seem to inhibit this isozyme at clinically attained plasma concentrations.

4.6 Pregnancy And Lactation

Pregnancy

Apart from epidural administration for obstetrical use, there are no adequate data on the use of ropivacaine in human pregnancy. Experimental animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/fœtal development, parturition or postnatal development (see section 5.3 Preclinical safety data).

Lactation

There are no data available concerning the excretion of ropivacaine into human milk.

4.7 Effects On Ability To Drive And Use Machines

No data are available. Depending on the dose, local anaesthetics may have a minor influence on mental function and co-ordination even in the absence of overt CNS toxicity and may temporarily impair locomotion and alertness.

4.8 Undesirable Effects

General

The adverse reaction profile for Naropin is similar to those for other long acting local anaesthetics of the amide type. Adverse drug reactions should be distinguished from the physiological effects of the nerve block itself e.g. a decrease in blood pressure and bradycardia during spinal/epidural block.

Table of adverse drug reactions

Within each system organ class, the ADRs have been ranked under the headings of frequency, most frequent reactions first.

Very common (>1/10)	Vascular Disorders	Hypotension
	Gastrointestinal Disorders	Nausea
Common (>1/100)	Nervous System Disorders	Headache, paraesthesia, dizziness
	Cardiac Disorders	Bradycardia, tachycardia
	Vascular Disorders	Hypertension
	Gastrointestinal Disorders	Vomiting
	Renal and Urinary Disorders	Urinary retention
	General Disorder and Administration Site Conditions	Temperature elevation, rigor, back pain
Uncommon (>1/1,000)	Psychiatric Disorders	Anxiety
	Nervous System Disorders	Symptoms of CNS toxicity (convulsions, grand mal convulsions, seizures, light headedness, circumoral paraesthesia, numbness of the tongue, hyperacusis, tinnitus, visual disturbances, dysarthria, muscular twitching, tremor)^* , Hypoaesthesia.
	Vascular Disorders	Syncope
	Respiratory, Thoracic and Mediastinal Disorders	Dyspnoea
	General Disorders and Administration Site Conditions	Hypothermia
Rare (>1/10,000)	Cardiac Disorders	Cardiac arrest, cardiac arrhythmias
	General Disorder and Administration Site Conditions	Allergic reactions (anaphylactic reactions, angioneurotic oedema and urticaria)

^* These symptoms usually occur because of inadvertent intravascular injection, overdose or rapid absorption, see section 4.9

Class-related adverse drug reactions:

Neurological complications

Neuropathy and spinal cord dysfunction (e.g. anterior spinal artery syndrome, arachnoiditis, cauda equina), which may result in rare cases of permanent sequelae, have been associated with regional anaesthesia, regardless of the local anaesthetic used.

Total spinal block

Total spinal block may occur if an epidural dose is inadvertently administered intrathecally.

Acute systemic toxicity

Systemic toxic reactions primarily involve the central nervous system (CNS) and the cardiovascular system (CVS). Such reactions are caused by high blood concentration of a local anaesthetic, which may appear due to (accidental) intravascular injection, overdose or exceptionally rapid absorption from highly vascularized areas, see also section 4.4. CNS reactions are similar for all amide local anaesthetics, while cardiac reactions are more dependent on the drug, both quantitatively and qualitatively.

Central nervous system toxicity

Central nervous system toxicity is a graded response with symptoms and signs of escalating severity. Initially symptoms such as visual or hearing disturbances, perioral numbness, dizziness, light-headedness, tingling and paraesthesia are seen. Dysarthria, muscular rigidity and muscular twitching are more serious and may precede the onset of generalised convulsions. These signs must not be mistaken for neurotic behaviour. Unconsciousness and grand mal convulsions may follow, which may last from a few seconds to several minutes. Hypoxia and hypercarbia occur rapidly during convulsions due to the increased muscular activity, together with the interference with respiration. In severe cases even apnoea may occur. The respiratory and metabolic acidosis increases and extends the toxic effects of local anaesthetics.

Recovery follows the redistribution of the local anaesthetic drug from the central nervous system and subsequent metabolism and excretion. Recovery may be rapid unless large amounts of the drug have been injected.

Cardiovascular system toxicity

Cardiovascular toxicity indicates a more severe situation. Hypotension, bradycardia, arrhythmia and even cardiac arrest may occur as a result of high systemic concentrations of local anaesthetics. In volunteers the intravenous infusion of ropivacaine resulted in signs of depression of conductivity and contractility.

Cardiovascular toxic effects are generally preceded by signs of toxicity in the central nervous system, unless the patient is receiving a general anaesthetic or is heavily sedated with drugs such as benzodiazepines or barbiturates.

In children, early signs of local anaesthetic toxicity may be difficult to detect since they may not be able to verbally express them. See also section 4.4.

Treatment of acute systemic toxicity

See section 4.9 Overdose.

4.9 Overdose

Symptoms:

Accidental intravascular injections of local anaesthetics may cause immediate (within seconds to a few minutes) systemic toxic reactions. In the event of overdose, peak plasma concentrations may not be reached for one to two hours, depending on the site of the injection, and signs of toxicity may thus be delayed. (See section 4.8 Acute systemic toxicity, Central nervous system toxicity and Cardiovascular system toxicity).

Treatment

If signs of acute systemic toxicity appear, injection of the local anaesthetic should be stopped immediately and CNS symptoms (convulsions, CNS depression) must promptly be treated with appropriate airway/respiratory support and the administration of anticonvulsant drugs.

If circulatory arrest should occur, immediate cardiopulmonary resuscitation should be instituted. Optimal oxygenation and ventilation and circulatory support as well as treatment of acidosis are of vital importance.

If cardiovascular depression occurs (hypotension, bradycardia), appropriate treatment with intravenous fluids, vasopressor, and or inotropic agents should be considered. Children should be given doses commensurate with age and weight.

Should cardiac arrest occur, a successful outcome may require prolonged resuscitative efforts.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Anaesthetics, local, Amides

ATC code: N01B B09

Ropivacaine is a long-acting, amide-type local anaesthetic with both anaesthetic and analgesic effects. At high doses Naropin produces surgical anaesthesia, while at lower doses it produces sensory block with limited and non-progressive motor block.

The mechanism is a reversible reduction of the membrane permeability of the nerve fibre to sodium ions. Consequently the depolarisation velocity is decreased and the excitable threshold increased, resulting in a local blockade of nerve impulses.

The most characteristic property of ropivacaine is the long duration of action. Onset and duration of the local anaesthetic efficacy are dependent upon the administration site and dose, but are not influenced by the presence of a vasoconstrictor (e.g. adrenaline (epinephrine)). For details concerning the onset and duration of action of Naropin, see table under posology and method of administration.

Healthy volunteers exposed to intravenous infusions tolerated ropivacaine well at low doses and with expected CNS symptoms at the maximum tolerated dose. The clinical experience with this drug indicates a good margin of safety when adequately used in recommended doses.

5.2 Pharmacokinetic Properties

Ropivacaine has a chiral center and is available as the pure S-(-)-enantiomer. It is highly lipid-soluble. All metabolites have a local anaesthetic effect but of considerably lower potency and shorter duration than that of ropivacaine.

The plasma concentration of ropivacaine depends upon the dose , the route of administration and the vascularity of the injection site. Ropivacaine follows linear pharmacokinetics and the C_max is proportional to the dose.

Ropivacaine shows complete and biphasic absorption from the epidural space with half-lives of the two phases of the order of 14 min and 4 h in adults. The slow absorption is the rate-limiting factor in the elimination of ropivacaine, which explains why the apparent elimination half-life is longer after epidural than after intravenous administration.

Ropivacaine has a mean total plasma clearance in the order of 440 ml/min, a renal clearance of 1 ml/min, a volume of distribution at steady state of 47 litres and a terminal half-life of 1.8 h after iv administration. Ropivacaine has an intermediate hepatic extraction ratio of about 0.4. It is mainly bound to α₁- acid glycoprotein in plasma with an unbound fraction of about 6%.

An increase in total plasma concentrations during continuous epidural infusion has been observed, related to a postoperative increase of α₁- acid glycoprotein.

Variations in unbound, i.e. pharmacologically active, concentration have been much less than in total plasma concentration.

Ropivacaine readily crosses the placenta and equilibrium in regard to unbound concentration will be rapidly reached. The degree of plasma protein binding in the foetus is less than in the mother, which results in lower total plasma concentrations in the foetus than in the mother.

Ropivacaine is extensively metabolised, predominantly by aromatic hydroxylation. In total, 86% of the dose is excreted in the urine after intravenous administration, of which only about 1% relates to unchanged drug. The major metabolite is 3-hydroxy-ropivacaine, about 37% of which is excreted in the urine, mainly conjugated. Urinary excretion of 4-hydroxy-ropivacaine, the N-dealkylated metabolite and the 4-hydroxy-dealkylated accounts for 1–3%. Conjugated and unconjugated 3-hydroxy-ropivacaine shows only detectable concentrations in plasma.

There is no evidence of in vivo racemisation of ropivacaine.

5.3 Preclinical Safety Data

Based on conventional studies of safety pharmacology, single and repeated dose toxicity, reproduction toxicity, mutagenic potential and local toxicity, no hazards for humans were identified other than those which can be expected on the basis of the pharmacodynamic action of high doses of ropivacaine (e.g. CNS signs, including convulsions, and cardiotoxicity).

6. Pharmaceutical Particulars

6.1 List Of Excipients

Sodium chloride

Hydrochloric acid

Sodium hydroxide

Water for injection

6.2 Incompatibilities

In alkaline solutions precipitation may occur as ropivacaine shows poor solubility at pH > 6

6.3 Shelf Life

3 years.

Shelf life after first opening:

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 2–8°C.

6.4 Special Precautions For Storage

Do not store above 30°C. Do not freeze.

For storage after opening, see section 6.3.

6.5 Nature And Contents Of Container

10 ml polypropylene ampoules (Polyamp) in packs of 5 and 10.

10 ml polypropylene ampoules (Polyamp) in sterile blister packs of 5 and 10.

20 ml polypropylene ampoules (Polyamp) in packs of 5 and 10.

20 ml polypropylene ampoules (Polyamp) in sterile blister packs of 5 and 10.

The polypropylene ampoules (Polyamp) are specially designed to fit Luer lock and Luer fit syringes.

6.6 Special Precautions For Disposal And Other Handling

Naropin products are preservative-free and are intended for single use only. Discard any unused solution.

The intact container must not be re-autoclaved. A blistered container should be chosen when a sterile outside is required.

7. Marketing Authorisation Holder

AstraZeneca UK Ltd.,

600 Capability Green,

Luton, LU1 3LU, UK.

8. Marketing Authorisation Number(S)

PL 17901/0150

9. Date Of First Authorisation/Renewal Of The Authorisation

Date of first authorisation: 3^rd October 1995

Date of last renewal: 15^th September 2005

10. Date Of Revision Of The Text

15^th August 2008

Thursday, 19 July 2012

Anticholinesterase Poisoning Medications

Drugs associated with Anticholinesterase Poisoning

The following drugs and medications are in some way related to, or used in the treatment of Anticholinesterase Poisoning. This service should be used as a supplement to, and NOT a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners.

Topics under Anticholinesterase Poisoning

Anticholinesterase Overdose (1 drug)

Drug List:

Atreza

Atropen

Sal-Tropine

Thursday, 12 July 2012

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
Brands: Fosamax, Fosamax Plus D

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 Alendronate Sodium

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 women¹ 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

Alendronate Sodium 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 Alendronate Sodium

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 manifestations¹ 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 Alendronate Sodium

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 alendronate^a	Wait at least ≥30 minutes after taking alendronate before taking any other oral medications^a
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

Alendronate Sodium 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]

Tuesday, 10 July 2012

Synalar Mild

Generic Name: fluocinolone (Topical application route)

floo-oh-SIN-oh-lone a-SEET-oh-nide

Commonly used brand name(s)

In the U.S.

Capex

Derma-Smoothe/FS

Synalar

In Canada

Fluoderm Mild Cream

Fluoderm Mild Ointment

Fluoderm Regular Cream

Fluoderm Regular Ointment

Fluolar Mild

Fluolar Regular

Fluonide Mild-Cream

Synalar Mild

Synalar Regular

Synamol

Available Dosage Forms:

Cream

Solution

Shampoo

Ointment

Lotion

Gel/Jelly

Therapeutic Class: Corticosteroid, Intermediate

Pharmacologic Class: Fluocinolone

Uses For Synalar Mild

Fluocinolone topical is used to relieve redness, itching, swelling, or other discomfort caused by skin conditions. Fluocinolone scalp oil is used to treat psoriasis of the scalp, and fluocinolone shampoo for seborrheic dermatitis of the scalp. This medicine is a corticosteroid (cortisone-like medicine or steroid).

This medicine is available only with your doctor's prescription.

Before Using Synalar Mild

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of fluocinolone topical in the pediatric population. However, because of this medicine's toxicity, it should be used with caution. Children may absorb large amounts through the skin, which can cause serious side effects. If your child is using this medicine, follow your doctor's instructions very carefully. For the body oil form, safety and efficacy in children 3 months of age and younger have not been established.

Geriatric

No information is available on the relationship of age to the effects of fluocinolone topical in geriatric patients.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Proper Use of fluocinolone

This section provides information on the proper use of a number of products that contain fluocinolone. It may not be specific to Synalar Mild. Please read with care.

It is very important that you use this medicine only as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered. To do so may cause unwanted side effects or skin irritation.

This medicine is for use on the skin only. Do not get it in your eyes. Do not use it on skin areas that have cuts, scrapes, or burns. If it does get on these areas, rinse it off right away with water.

This medicine should only be used for skin conditions that your doctor is treating. Check with your doctor before using it for other conditions, especially if you think that a skin infection may be present. This medicine should not be used to treat certain kinds of skin infections or conditions, such as severe burns.

To use cream, ointment, solution, and body oil:

Wash your hands with soap and water before and after using this medicine.

Apply a thin layer of this medicine to the affected area of the skin or scalp. Rub it in gently.

Do not bandage or otherwise wrap the skin being treated unless directed to do so by your doctor.

If the medicine is applied to the diaper area of an infant, do not use tight-fitting diapers or plastic pants unless directed to do so by your doctor.

If your doctor ordered an occlusive dressing or airtight covering to be applied over the medicine, make sure you know how to apply it. Occlusive dressings increase the amount of medicine absorbed through your skin, so use them only as directed. If you have any questions about this, check with your doctor.

To use shampoo:

Wash your hands with soap and water before and after using this medicine.

Wet hair and scalp thoroughly.

Shake the container well, and apply about an ounce of the shampoo to the scalp area.

Work the shampoo into a lather, and leave on the scalp for 5 minutes.

Wash hair and scalp thoroughly with water.

To use scalp oil:

Wash your hands with soap and water before and after using this medicine.

Wet hair and scalp thoroughly.

Apply a thin layer of this medicine to the affected area of the scalp. Rub it in gently.

Cover the scalp with the supplied shower cap overnight for at least 4 hours.

Wash hair with regular shampoo and clean well.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For redness, itching, and swelling of the skin:
- For topical dosage form (cream, ointment, and solution):
  - Adults—Apply to the affected areas of the skin three to four times a day.
  - Children—Use and dose must be determined by your doctor.
- For topical dosage form (body oil):
  - Adults—Apply to the affected areas of the skin three times a day for up to 2 weeks.
  - Children 3 months of age and older—Apply to the affected areas two times a day for up to 4 weeks.

For seborrheic dermatitis:
- For topical dosage form (shampoo):
  - Adults—Use on the scalp area once a day.
  - Children—Use and dose must be determined by your doctor.

For scalp psoriasis:
- For topical dosage form (scalp oil):
  - Adults—Apply to the affected areas of the scalp and leave overnight.
  - Children 2 years of age and older—Apply to the affected areas 2 times a day for up to 4 weeks.

Missed Dose

If you miss a dose of this medicine, apply it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using Synalar Mild

It is very important that your doctor check the progress of you or your child at regular visits for any unwanted effects that may be caused by this medicine.

If your or your child's symptoms do not improve within a few days, or if they become worse, check with your doctor.

Using too much of this medicine or using it for a long time may increase your risk of having adrenal gland problems. The risk is greater for children and patients who use large amounts for a long time. Talk to your doctor right away if you or your child have more than one of these symptoms while you are using this medicine: blurred vision; dizziness or fainting; a fast, irregular, or pounding heartbeat; increased thirst or urination; irritability; or unusual tiredness or weakness.

Stop using this medicine and check with your doctor right away if you or your child have a skin rash, burning, stinging, swelling, or irritation on the skin.

Synalar Mild Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

Body aches or pain

congestion

cough

dryness or soreness of the throat

fever

headache

hoarseness

lightening of normal skin color

lightening of treated areas of dark skin

sore throat

stuffy or runny nose

tender, swollen glands in the neck

trouble swallowing

unusual tiredness or weakness

voice changes

Less common

Acne or pimples

accumulation of pus

blistering, crusting, irritation, itching, or reddening of the skin

burning, itching, and pain in hairy areas, or pus at the root of the hair

burning and itching of the skin with pinhead-sized red blisters

change in hearing

cracked, dry, scaly skin

diarrhea

dry skin

earache or pain in the ear

ear drainage

flushing or redness of the skin

darkening of the skin

itching, scaling, severe redness, soreness, or swelling of the skin

itchy, raised, round, smooth, skin-colored bumps found on just one area of the body

ooze thick white fluid

raised, dark red, wart-like spots on skin, especially when used on the face

redness or swelling in the ear

skin irritation

skin rash, encrusted, scaly and oozing

spots on your skin resembling a blister or pimple

swelling

swollen, red, tender area of infection

thickened patches of the skin

vomiting

Incidence not known

Redness and scaling around the mouth

thinning, weakness, or wasting away of the skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common

Changes in skin color

shiny skin

Incidence not known

increased hair growth on the forehead, back, arms, and legs

reddish purple lines on the arms, face, legs, trunk, or groin

softening of the skin

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also: Synalar side effects (in more detail)

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More Synalar Mild resources

Synalar Mild Side Effects (in more detail)
Synalar Mild Use in Pregnancy & Breastfeeding
Synalar Mild Drug Interactions
Synalar Mild Support Group
2 Reviews for Synalar - Add your own review/rating

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Tuesday, 3 July 2012

Betadine Vaginal Cleansing (VC) Kit (Molnlycke Health Care )

1. Name Of The Medicinal Product

Betadine VC Kit 10% w/v.

2. Qualitative And Quantitative Composition

Povidone Iodine USP 10% w/v.

3. Pharmaceutical Form

Solution.

4. Clinical Particulars

4.1 Therapeutic Indications

As a vaginal cleanser in the treatment of vaginitis due to candidal, trichomonal, non-specific or mixed infections and for pre-operative preparation of the vagina.

4.2 Posology And Method Of Administration

For intravaginal use. Adults and the elderly: Once a day (preferably in the morning) for a 14 day period, including days of menstruation. The Betadine VC Concentrate should be diluted 1:10 using the measuring cap, and used according to the patient instruction leaflet provided. The applicators should only be used for the administration of the diluted VC Kit solution. This product may be used in combination with Betadine Vaginal Pessaries. Children: Contra-indicated for use in pre-pubertal children.

4.3 Contraindications

Known or suspected iodine hypersensitivity. Regular use is contra-indicated in patients and users with thyroid disorders (in particular nodular colloid goitre, endemic goitre and Hashimoto's thyroiditis).

4.4 Special Warnings And Precautions For Use

Special caution is needed when regular applications to broken skin are made to patients with pre-existing renal insufficiency. Regular use should be avoided in patients on concurrent lithium therapy.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Absorption of iodine from povidone iodine through either intact or broken skin may interfere with thyroid function tests. Contamination with povidone iodine of several types of tests for the detection of occult blood in faeces or blood in urine may produce false-positive results.

4.6 Pregnancy And Lactation

Regular use of povidone iodine should be avoided in pregnant or lactating women as absorbed iodine can cross the placental barrier and can be secreted into breast milk. Although no adverse effects have been reported from limited use, caution should be recommended and therapeutic benefit must be balanced against possible effects of the absorption of iodine on foetal thyroid function and development.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

If local irritation, redness or swelling develops, discontinue treatment. Iodine is absorbed from the vagina and following prolonged use, thyroid dysfunction may develop. The product may be spermicidal and should not be used when conception is desired.

4.9 Overdose

Excess iodine can produce goitre and hypothyroidism or hyperthyroidism. In the case of deliberate or accidental ingestion of large quantities of Betadine, symptomatic and supportive treatment should be provided with special attention to electrolyte balance and renal and thyroid function.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Povidone iodine is a complex of iodine which retains the broad spectrum germicidal activity of elemental iodine without its disadvantages. The germicidal activity is maintained in the presence of blood, pus, serum and necrotic tissue.

5.2 Pharmacokinetic Properties

Betadine VC Concentrate is applied topically to the affected area.

5.3 Preclinical Safety Data

None stated.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Nonoxynol 9; Fleuroma Bouquet 477; purified water.

6.2 Incompatibilities

Compatibility with barrier contraceptives has not been established. Therefore this product should not be used with such methods of contraception as their reliability may be affected.

6.3 Shelf Life

36 months.

6.4 Special Precautions For Storage

Store at or below 25^oC.

6.5 Nature And Contents Of Container

Carton containing a white polypropylene container with a white polypropylene wadless cap containing 250ml Betadine VC Concentrate, an empty turquoise low density polypropylene squeeze bottle and a vaginal applicator.

6.6 Special Precautions For Disposal And Other Handling

None stated.

7. Marketing Authorisation Holder

Seton Healthcare Group plc, Tubiton House, Oldham, OL1 3HS.

8. Marketing Authorisation Number(S)

PL 0223/0020.

9. Date Of First Authorisation/Renewal Of The Authorisation

28^th April 1993 / 17^th November 1998.

10. Date Of Revision Of The Text

April 2003.