Tramadol (Dosing, Interaction, Side Effect, Administration, Etc..)

Dosing:

Adult Dose

:
Important Note:
Beers Criteria:
Use caution or

avoid use

as potentially inappropriate in older adults.

Orphan drug designation:
Treatment of painful HIV-associated neuropathy
Management of postherpetic neuralgia

Dental pain:
50; 70; or 100 mg orally as a

single dose

Pain; chronic; moderate to moderately severe in patients requiring around-the-clock treatment for an extended period of time:

Extended-release tablets

for patients not currently on tramadol immediate-release products:
100 mg orally once daily; may titrate up by 100-mg increments every 2 to 3 days as necessary; maximum 300 mg/day.

Extended-release tablets or capsules for patients not currently on tramadol immediate-release products:
100 mg orally once daily; may titrate up by 100-mg increments every 5 days as necessary; maximum 300 mg/day.

Extended-release tablets or capsules; for patients currently on tramadol immediate-release products (IR):
Calculate 24-hour tramadol

IR dose

and initiate a total

daily dose

rounded down to the nearest 100-mg increment; maximum 300 mg/day.

Pain (Moderate to Severe):

Tramadol hydrochloride

oral disintegrating tablets

have been discontinued from the market.

Pain (Moderate to Severe); Not responsive to non-narcotic analgesics:
(

Immediate-release tablets

)
Initial; 25 mg/day orally every morning; titrated in 25-mg increments as separate doses every 3 days to reach 100 mg/day (25 mg 4 times daily); may increase total daily dose by 50 mg every 3 days as tolerated to reach 200 mg/day (50 mg 4 times daily)

(Immediate-release tablets)
Maintenance; 50 to 100 mg orally every 4 to 6 hours as needed following initial titration; maximum 400 mg/day

(Immediate-release tablets)
Rapid analgesic onset; 50 to 100 mg orally every 4 to 6 hours as needed without initial titration; maximum 400 mg/day

(Immediate-release tablets)
Discontinuation; decrease

dose

by 25% to 50% every 2 to 4 days; if signs or symptoms of withdrawal develop; raise the dose and taper more slowly

Pediatric Dose

:
Important Note:
Beers Criteria:
Use caution or avoid use as potentially inappropriate in older adults.

Orphan drug designation:
Treatment of painful HIV-associated neuropathy
Management of postherpetic neuralgia

General Dosage Information:
(Immediate-release tablets;

extended release tablets

and capsules) Safety and efficacy in pediatric patients have not been established
Life-threatening respiratory depression and death have occurred in children who received tramadol. Death was most often associated with post-tonsillectomy or adenoidectomy; especially in patients who were ultra-rapid metabolizers of codeine (i.e.; multiple copies of the gene for CYP2D6). Children with sleep apnea may be especially sensitive to the respiratory depressant

effects of tramadol

Use is contraindicated for all children younger than 12 years
Use is contraindicated for postoperative pain management in pediatric patients of any age undergoing tonsillectomy and/or adenoidectomy
Avoid use in adolescents 12 to 18 years who have risk factors that may increase the respiratory depressant effects of tramadol. Risk factors include postoperative status; obstructive sleep apnea; obesity and other conditions associated with hypoventilation syndromes; concomitant

use of

other medications that cause respiratory depression; and severe pulmonary disease
Use the

lowest effective dose

for the shortest amount of time and inform patients and caregivers about the risks and signs of

opioid overdose

Pain (Moderate to Severe); Not responsive to non-narcotic analgesics:
(Immediate-release tablets; 17 years and older)
Initial; 25 mg/day orally every morning; titrated in 25mg increments as

separate doses

every 3 days to reach 100 mg/day (25 mg 4 times daily); may increase total daily dose by 50 mg every 3 days as tolerated to reach 200 mg/day (50 mg 4 times daily)

(Immediate-release tablets; 17 years and older):
Maintenance; 50 to 100 mg orally every 4 to 6 hours as needed following initial titration; maximum 400 mg/day

(Immediate-release tablets; 17 years and older):
Rapid analgesic onset; 50 to 100mg orally every 4 to 6 hours as needed without initial titration; maximum 400 mg/day

(Immediate-release tablets; 17 years and older):
Discontinuation;

decrease dose

by 25% to 50% every 2 to 4 days; if signs or symptoms of withdrawal develop; raise the dose and taper more slowly

(12 years or older):
Contraindicated if

used for

postoperative pain management of tonsillectomy and/or adenoidectomy

Indications:
FDA-LABELED INDICATIONS:
Dental pain
Pain; chronic; moderate to moderately severe in patients requiring around-the-clock treatment for an extended period of time
Pain (Moderate to Severe)
Pain (Moderate to Severe); Not responsive to non-narcotic analgesics

NON FDA-LABELED INDICATIONS:
Anesthesia; Adjunct
Cancer pain

Mechanism Of Action:

Tramadol HCl

is a centrally-acting synthetic opioid analgesic that exerts its effect through the binding of parent drug and O-desmethyl-tramadol (M1) metabolite to mu-opioid receptors and through the weak inhibition of norepinephrine and serotonin reuptake

Adverse Effect:
Common:
Dermatologic:
Flushing (7.7% to 15.8%)
Pruritus (3% to 11.9%)

Gastrointestinal:
Constipation (10% to 46%)
Nausea (13% to 40%)
Vomiting (3% to 17%)
Xerostomia (1% to 10%)

Neurologic:
Dizziness (7% to 33%)
Headache (3% to 32%)
Insomnia (1% to 10.9%)
Somnolence (4% to 25%)

Serious
Cardiovascular:
Myocardial infarction (0.5% to less than 1%)

Endocrine metabolic:
Hypoglycemia (Very rare)

Gastrointestinal:
Pancreatitis (0.5% to less than 1%)

Immunologic:
Anaphylactoid reaction (less than 1%)

Neurologic:
Seizure

Respiratory:
Difficulty breathing
Dyspnea (less than 5%)
Respiratory depression

Other:
Serotonin syndrome (Less than 1%)

Contraindication:
Significant respiratory depression in unmonitored settings or without resuscitative equipment
Acute intoxication with alcohol; hypnotics; narcotics; centrally acting analgesics; opioids; or psychotropic drugs; may worsen CNS and respiratory depression
Acute or severe bronchial asthma; in unmonitored settings or without resuscitative equipment Children younger than 12 years
Postoperative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy

Hypercapnia:
Hypersensitivity to Opioids; tramadol hydrochloride; or any other components of the product
Known or suspected gastrointestinal obstruction; including paralytic ileus.,
Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs with the last 14 days

Interaction:
Inhibitors of CYP2D6:
The concomitant

use of tramadol

hydrochloride and CYP2D6 inhibitors may result in an increase in the

plasma concentration of tramadol

and a decrease in the plasma concentration of M1; particularly when an inhibitor is added after a stable

dose of tramadol hydrochloride

is achieved. Since M1 is a more potent µ-opioid agonist; decreased M1 exposure could result in decreased therapeutic effects; and may result in signs and symptoms of opioid withdrawal in patients who had developed physical dependence to tramadol. Increased tramadol exposure can result in increased or prolonged therapeutic effects and increased risk for serious adverse events including seizures and serotonin syndrome., After stopping a CYP2D6 inhibitor; as the effects of the inhibitor decline; the

tramadol plasma concentration

will decrease and the M1 plasma concentration will increase which could increase or prolong therapeutic effects but also increase adverse reactions related to opioid toxicity; and may cause potentially fatal respiratory depression

Inhibitors of CYP3A4:
The concomitant

use of tramadol hydrochloride

and CYP3A4 inhibitors can increase the plasma concentration of tramadol and may result in a greater amount of metabolism via CYP2D6 and greater levels of M1. Follow patients closely for increased risk of serious adverse events including seizures and serotonin syndrome; and adverse reactions related to opioid toxicity including potentially fatal respiratory depression; particularly when an inhibitor is added after a

stable dose of tramadol hydrochloride

is achieved.
After stopping a CYP3A4 inhibitor; as the effects of the inhibitor decline; the tramadol plasma concentration will decrease resulting in decreased opioid efficacy and possibly signs and symptoms of opioid withdrawal in patients who had developed physical dependence to tramadol.

CYP3A4 Inducers:
The concomitant

use of tramadol

hydrochloride and CYP3A4 inducers can decrease the plasma concentration of tramadol; resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to tramadol After stopping a CYP3A4 inducer; as the effects of the induc
er decline; the tramadol plasma concentration will increase which could increase or prolong both the therapeutic effects and adverse reactions; and may cause seizures and serotonin syndrome; and potentially fatal respiratory depression

Benzodiazepines and Other Central Nervous System (CNS) Depressants:
Due to additive pharmacologic effect; the concomitant

use of benzodiazepines

or other CNS depressants; including alcohol; can increase the risk of hypotension; respiratory depression; profound sedation; coma; and death.

Examples: Benzodiazepines and other sedatives/hypnotics; anxiolytics; tranquilizers; muscle relaxants; general anesthetics; antipsychotics; other opioids; alcohol

Serotonergic Drugs:
The concomitant

use of opioids

with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome

Examples: Selective serotonin reuptake inhibitors (SSRIs); serotonin and norepinephrine reuptake inhibitors (SNRIs); tricyclic antidepressants (TCAs); triptans; 5-HT3 receptor antagonists; drugs that affect the serotonin neurotransmitter system (e.g.; mirtazapine; trazodone; tramadol); monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others; such as linezolid and intravenous methylene blue)

Monoamine Oxidase Inhibitors (MAOIs):
MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g.; respiratory depression; coma)
Examples: phenelzine; tranylcypromine; linezolid

Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics:
May reduce the

analgesic effect of tramadol

hydrochloride and/or precipitate withdrawal symptoms Examples: butorphanol; nalbuphine; pentazocine; buprenorphine

Muscle Relaxants:
Tramadol may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression

Diuretics:
Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone

Anticholinergic Drugs:
The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation; which may lead to paralytic ileus

Digoxin:
Post-marketing surveillance of tramadol has revealed rare reports of digoxin toxicity

Warfarin:
Post-marketing surveillance of tramadol has revealed rare reports of alteration of warfarin effect; including elevation of prothrombin times

Phamacokinetics:
Absorption:
Oral:
Time for Maximum Plasma Concentration (Tmax):
1 to 2.3 hours
Geriatrics: 2.1 hours
Hepatic impairment: 1.9 hours
Extended-release capsules/tablet: 4 to 12 hours

Bioavailability:
Immediate-release tablet: 75%
Extended-release tablet: approximately 85% to 95% relative to immediate-release tablet

Effects of food:
Immediate-release tablet: None
Orally-disintegrating tablet: delayed Tmax; rate and extent of absorption not affected
Extended-release tablet: Cmax increased 54% to 67%; but AUC not affected
Extended-release capsule: None
Extended-release tablet: AUC decreased 28%; Cmax decreased 16%; Tmax increased 3 hours

Distribution:
Plasma Protein binding: Approximately 20%

Volume of Distribution (Vd):
Female: 2.9 L/kg
Male: 2.6 L/kg

Metabolism:
Hepatic: extensive via CYP2D6 and CYP3A4; conjugation; N and O demethylation; and glucuronidation or sulfation

O desmethyl tramadol (M1):active
Substrate of CYP3A4 and CYP2D6.

Excretion:
Renal:
60% as metabolite
Approximately 30% unchanged.

Dialyzable:
Less than 7% removed over 4 hours.
Hemodialysis: No

Total body clearance:
Adults: 5.9 mL/min/kg
Elderly: 6.89 mL/min/kg
Hepatic impairment: 4.23 mL/min/kg
Oral disintegrating tablet; renal impairment: 3.73 to 4.23 mL/min/kg

Elimination:
Immediate-release: adults; 5.6 to 6.7 hours
Extended-release: 6.5 to 10 hours

Immediate-release:
Geriatric (aged 75 years and older); 7 hours
Hepatic impairment; 13 hours
IV: renal impairment (CrCl less than 30 mL/min); 10.6 hours to 11 hours.
O-desmethyl-tramadol (M1);
Immediate-release: 6.7 to 7 hours
Extended-release: 7.5 to 11 hours
Immediate-release: hepatic impairment; 18.5 to 19 hours
IV: renal impairment (CrCl less than 30 mL/min); 11.5 to 16.9 hours

Precaution:
Beers Criteria:
Avoid

use in older patients

with chronic seizures or epilepsy as seizure threshold may be decreased. Avoid use in older patients with a history of falls or fractures as ataxia; impaired psychomotor function; syncope and falls may occur (excludes patients requiring pain management due to recent fractures or joint replacement). If use is necessary; consider reducing use of other CNS-active agents that increase risk of falls and fractures and implement other strategies to reduce risk of falls.

Addiction:
High risk of abuse; addiction; or misuse; especially in patients with a personal or family history of substance abuse or mental illness; monitoring recommended

Cardiovascular:
Severe hypotension and syncope may occur; with increased risk in patients whose ability to maintain blood pressure has been compromised or with concurrent administration of certain central nervous system depressants; monitoring recommended; especially at start of therapy and during dosage adjustments
Circulatory shock; avoid use.

Concomitant use:
Avoid alcohol
Carbamazepine is not recommended
Avoid use with agonist/antagonist or partial agonist analgesics.

Endocrine and metabolic:
Opioids may rarely lead to adrenal insufficiency due to inadequate amounts of cortisol. If adrenal insufficiency is suspected; perform diagnostic testing; treat with corticosteroids if confirmed; wean patient off of opioid if appropriate; and continue to assess adrenal function.

Gastrointestinal:
Use caution in patients with acute abdominal conditions as clinical course may be obscured Spasm of the sphincter of Oddi may occur; monitoring recommended in patients with biliary tract disease; including pancreatitis.

Hepatic:
Cirrhosis;

dose adjustment

may be necessary
Use caution in patients with any degree Tramadol hepatic impairment; use not recommended for tramadol hydrochloride extended-release.

Immunologic:
Anaphylactoid reactions; including serious and rarely fatal reactions often following the

first dose

; have been reported.

Misuse or abuse:
Potential for abuse; misuse; and diversion exists
History of misuse increases suicide risk.

Neurologic:
Potentially life-threatening serotonin syndrome may occur; particularly with concomitant use of serotonergic drugs
Seizures have been reported; especially with doses exceeding recommended range; with concomitant use of drugs that reduce seizure threshold; in patients with epilepsy; a history of seizures; or other risks for seizures; including head trauma; certain metabolic disorders; alcohol and drug withdrawal; and CNS infections.
Increased intracranial pressure or head injury may result in exaggerated carbon dioxide retention and secondary elevation of cerebrospinal fluid pressure; miosis from

tramadol therapy

may obscure intracranial pathology
Respiratory depression and sedation due to carbon dioxide retention may occur in patients with increased intracranial pressure; brain tumors; and head injury; monitoring recommended; especially at therapy initiation
Impaired consciousness or coma; avoid use.

Prolonged use:
Long-term use of Opioids may be associated with decreased sex hormone levels and symptoms such as reduced interest in sex; impotence; or infertility. Laboratory evaluation may be warranted.

Psychiatric:
Use is not recommended in patients who are suicidal or addiction-prone
Emotional disturbances or depression increases suicide risk.

Renal:
Severe renal impairment (CrCl less than 30 mL/min);

dose reduction

recommended for tramadol hydrochloride immediate-release and

orally disintegrating tablets

(ODT) and use not recommended with extended-release

formulations Tramadol

hydrochloride

Respiratory:
Respiratory depression may occur; with increased risk when

large doses

are administered with anesthetic medications or alcohol; or when

used

concomitantly with CNS depressants; consider alternative non-opioid analgesics.

Special populations:
Ambulatory patients may experience impaired mental or physical abilities; caution advised with potentially hazardous tasks.

Respiratory:
Life-threatening respiratory depression may occur; especially in patients with chronic pulmonary disease; including chronic obstructive pulmonary disease; cor pulmonale; decreased respiratory reserve; hypoxia; hypercapnia; or pre-existing respiratory depression; the elderly; cachectic; or debilitated patients; monitoring recommended; especially at start of therapy and during dosage., adjustments. Consider alternative; non-opioid therapy.

Special populations:
Breastfeeding while receiving

treatment with tramadol

is not recommended; especially in mothers who have the CYP2D6 ultra-rapid metabolizer genotype; due to serious adverse reactions in breastfed infants including sedation or respiratory depression that could result in death

Avoid use

in adolescents between 12 and 18 years of age who are obese or have respiratory conditions (e.g.; obstructive sleep apnea or compromised respiratory function) due to increased risk of respiratory adverse events
Patients over 75 years experience adverse events more frequently; start at low end of dosing range in patients older than 65 years
Phenylketone sensitivity; use of ODT not recommended

Withdrawal:
Abrupt discontinuation may induce withdrawal; taper recommended when discontinuing.

Pregnancy Category:
Fetal Risk cannot be ruled out.

Breast Feeding:
Infant risk has been demonstrated

Monitoring:
Pain reduction; improvement in ability to move

Evaluate maintenance of pain control: Continuously

Hypotension: With therapy initiation and dose adjustments in patients with compromised ability to maintain blood pressure

Increased seizure frequency or severity: In patients with a history of seizure disorder
Signs and symptoms of respiratory depression: Within the first 24 to 72 hours of therapy initiation and after

dose increases

; especially in the elderly; cachectic; debilitated; and those with chronic pulmonary disease or with concomitant use of other drugs that cause respiratory depression

Signs of sedation and respiratory depression: During therapy initiation in patients susceptible to intracranial effects of carbon dioxide retention (e.g.; pre-existing intracranial pressure; brain tumors; or head injuries)
Suicidal ideation or worsening depression

How To Take Or Administration:
Oral:
(Immediate-release tablets)
May be taken with or without food

(Extended-release tablets or capsules)
Do not crush, chew, or split; may be taken with or without food

Dosage Form:
Oral Capsule; Extended Release:
100 MG
150 MG
200 MG

Oral Tablet:
50 MG

Oral Tablet; Extended Release:
100 MG
200 MG
300 MG

Treatment:
MANAGEMENT OF MILD TO MODERATE TOXICITY:
Patients generally only need observation and supportive care

MANAGEMENT OF SEVERE TOXICITY:
Naloxone is the antidote indicated for significant CNS or respiratory depression. Orotracheal intubation for airway protection should be performed early in cases of obtundation and/or respiratory depression that do not respond to naloxone Treat seizures with benzodiazepines

Toxicology:
ADULTS:
In adults; 500 mg was the

lowest dose

associated with seizures; respiratory depression; agitation; tachycardia or hypertension. Adult fatalities have been reported after ingestion of 2.65 to 8.2 g tramadol without coingestants. An adult with a

tramadol overdose

developed a Brugada ECG pattern. An adult survived an estimated maximal ingestion of 10 g, but had a residual moderate cerebral deficit.

PEDIATRIC:
A teenager developed multiorgan dysfunction after ingesting

6 g of tramadol

, but recovered completely. Children have tolerated ingestions of up to 300 mg with mild toxicity; but experience is limited. Serotonin syndrome was observed in an 8-month old after ingesting

200 mg of tramadol

; recovery was uneventful. Severe toxicity has been reported in infants who received 100 mg rectally

Patient Counselling Or Clinical Teaching:
Tell patient to report symptoms of respiratory depression
Counsel patient to report symptoms of adrenal insufficiency
Instruct patient to avoid activities requiring mental alertness or coordination until drug effects are realized; as this drug may cause dizziness; somnolence; and impaired mental and physical abilities

Side effects

may include pruritus; dizziness; diarrhea; nausea; vomiting; headache; seizures; and rarely hallucinations
Tell patient to report symptoms of hypotension or syncope
Instruct patient; family members; and caregivers to report worsening depression; suicidal ideation; or unusual changes in behaviour
Advise patient to report symptoms of serotonin syndrome
Tell patient to report severe constipation
Advise patient against sudden discontinuation of drug; as this may precipitate withdrawal symptoms
Advise patient to avoid alcohol and other CNS depressants while taking this drug




tramadol Click Here for Download PDF file of Tramadol Hydrochloride

Atorvastatin (Dosing, Interaction, Side Effect, Administration, Etc..)

Dosing:

Adult Dose

:
Common Information:
Dosage range is 10 to 80 mg once daily; following

dose

initiation or titration; lipid level assessment should be done within 2 to 4 weeks

Disorder of cardiovascular system; in patients with multiple risk factors for coronary heart disease; Prophylaxis:
Initial; 10 to 20 mg ORALLY once daily
Initial 40 mg ORALLY once daily if reductions of greater than 45% in LDL-C are needed

Disorder of cardiovascular system; in patients with multiple risk factors for coronary heart disease; Prophylaxis - Type 2 diabetes mellitus:
Initial; 10 to 20 mg ORALLY once daily
Initial 40 mg ORALLY once daily if reductions of greater than 45% in LDL-C are needed

Disorder of cardiovascular system; Secondary; Prophylaxis:
Initial; 10 to 20 mg ORALLY once daily
Initially 40 mg ORALLY once daily if reductions of greater than 45% in LDL-C are needed

Familial hypercholesterolemia - homozygous; Adjunct:
10 to 80 mg ORALLY once daily with other lipid-lowering therapy

Familial type 3 hyperlipoproteinemia:
Initial; 10 to 20 mg ORALLY once daily; dosage range is 10 to 80 mg once daily; OR initial 40 mg ORALLY once daily if reductions of greater than 45% in LDL-C are needed.

Generalized atherosclerosis:
Arthrosclerosis regression:
80 mg orally daily with or without ezetimibe 10 mg orally daily (off-label dosage).

Hypercholesterolemia; primary (heterozygous familial and non-familial) and mixed dyslipidemia (Fredrickson types IIa and IIb):
Initial; 10 to 20 mg ORALLY once daily
Initial; 40 mg ORALLY once daily if reductions greater than 45% in LDL-C are needed; dosage range is 10 to 80 mg once daily

Hypertriglyceridemia:
Initial:
10 to 20 mg ORALLY once daily
Initial 40 mg ORALLY once daily of reductions of greater than 45% in LDL-C are needed.

Pediatric Dose

:
General Dosage Information:
Safety and efficacy not been established in pediatric patients younger than 10 years of age for the treatment of heterozygous familial hypercholesterolemia.

Hypercholesterolemia; primary (heterozygous familial and non-familial) and mixed dyslipidemia (Fredrickson types IIa and IIb):
Age 10 to 17 years:
initially 10 mg ORALLY daily; adjustments at intervals of 4-weeks or greater; up to Maximum 20 mg ORALLY daily; following

dose initiation

or titration; lipid level assessment should be done within 2 to 4 weeks
Age 6 to 10 years:
5 to 10 mg ORALLY daily has been

used in

one open-label; uncontrolled study.

Indications:
FDA-LABELED INDICATIONS:
Disorder of cardiovascular system; in patients with multiple risk factors for coronary heart disease; Prophylaxis
Disorder of cardiovascular system; in patients with multiple risk factors for coronary heart disease; Prophylaxis - Type 2 diabetes mellitus
Disorder of cardiovascular system; Secondary; Prophylaxis
Familial hypercholesterolemia - homozygous; Adjunct
Familial type 3 hyperlipoproteinemia
Hypercholesterolemia; primary (heterozygous familial and non-familial) and mixed dyslipidemia (Fredrickson types IIa and IIb)
Hypertriglyceridemia

NON-FDA LABELED INDICATIONS:
Antiviral drug adverse reaction; Antiretroviral – Hyperlipidemia
Cardiovascular event risk; Perioperative; Prophylaxis - Percutaneous coronary intervention
Diabetic retinopathy; Adjunct
Disorder of cardiovascular system; Primary; Prophylaxis
Dyslipidemia – Transplantation
Generalized atherosclerosis
Heart failure; chronic
Radiographic contrast agent nephropathy; Prophylaxis
Restenotic lesion of coronary artery; Prophylaxis
Secondary hypercholesterolemia

Mechanism Of Action

Atorvastatin calcium

selectively and competitively inhibits HMG-CoA reductase; a rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate; a sterol and cholesterol precursor.

Adverse Effect
Common:
Gastrointestinal:
Diarrhea (up to 14.1%)

Musculoskeletal:
Arthralgia (up to 11.7%)
Myalgia (up to 8.4%)

Renal:
Urinary tract infectious disease (up to 8%)

Respiratory:
Nasopharyngitis (8.3%)

Other:
Pain; in extremity (up to 9.3%)

Serious:
Dermatologic:
Dermatomyositis

Hepatic:
Increased liver enzymes (0.2% to 2.3%)
Liver failure

Immunologic:
Autoimmune disease
Systemic lupus erythematosus

Musculoskeletal:
Disorder of muscle
Rhabdomyolysis
Rupture of tendon

Neurologic:
Hemorrhagic cerebral infarction (2.3%)

Contraindication:
Active liver disease
Hypersensitivity to

atorvastatin

or any component of the product
Nursing mothers
Unexplained persistent elevation of serum transaminases
Women who are pregnant or may become pregnant; may cause fetal harm

Interaction:
The risk of myopathy during treatment with statins is increased with concurrent administration of fibric acid derivatives, lipidmodifying

doses

of niacin, cyclosporine, or strong CYP 3A4 inhibitors (e.g. clarithromycin, HIV protease inhibitors, and itraconazole)

Strong Inhibitors of CYP 3A4:
Atorvastatin calcium is metabolized by cytochrome P450 3A4. Concomitant

administration of atorvastatin

calcium with strong inhibitors of CYP 3A4 can lead to increases in

plasma concentrations of atorvastatin

. The extent of interaction and potentiation of effects depend on the variability of effect on CYP 3A4.

Clarithromycin:

Atorvastatin AUC was significantly increased with concomitant administration of atorvastatin calcium 80 mg with clarithromycin (500 mg twice daily) compared to that of atorvastatin calcium alone. Therefore, in patients taking clarithromycin, caution should be

used

when the

atorvastatin calcium dose

exceeds 20 mg

Combination of Protease Inhibitors:
Atorvastatin AUC was significantly increased with concomitant administration of

atorvastatin calcium 40 mg

with ritonavir plus saquinavir (400 mg twice daily) or

atorvastatin calcium 20 mg

with lopinavir plus ritonavir (400 mg + 100 mg twice daily) compared to that of atorvastatin calcium alone .Therefore, in patients taking HIV protease inhibitors, caution should be used when the

atorvastatin calcium dose

exceeds 20 mg

Itraconazole:
Atorvastatin AUC was significantly increased with concomitant administration of atorvastatin calcium 40 mg and itraconazole 200 mg.Therefore, in patients taking itraconazole, caution should be used when the

atorvastatin calcium dose

exceeds 20 mg

Grapefruit Juice:
Contains one or more components that inhibit CYP 3A4 and can increase plasma concentrations of atorvastatin, especially with excessive grapefruit juice consumption (>1.2 liters per day).

Cyclosporine:
Atorvastatin and atorvastatin-metabolites are substrates of the OATP1B1 transporter. Inhibitors of the OATP1B1 (e.g. cyclosporine) can increase the

bioavailability of atorvastatin

. Atorvastatin AUC was significantly increased with concomitant administration of

atorvastatin calcium 10 mg

and cyclosporine 5.2 mg/kg/day compared to that of atorvastatin calcium alone In cases where co-administration of atorvastatin calcium with cyclosporine is necessary, the

dose of atorvastatin calcium

should not exceed 10 mg

Rifampin or other Inducers of Cytochrome P450 3A4:
Concomitant administration of atorvastatin calcium with inducers of cytochrome P450 3A4 (e.g. efavirenz, rifampin) can lead to variable reductions in plasma concentrations of atorvastatin. Due to the dual interaction mechanism of rifampin, simultaneous co-administration of atorvastatin calcium with rifampin is recommended, as delayed administration of atorvastatin calcium after administration of rifampin has been associated with a significant reduction in

atorvastatin plasma concentrations

.

Digoxin:
When multiple doses of atorvastatin calcium and digoxin were co-administered, steady state plasma digoxin concentrations increased by approximately 20%

Patients taking digoxin should be monitored appropriately.
Oral Contraceptives:
Co-administration of atorvastatin calcium and an oral contraceptive increased AUC values for norethindrone and ethinyl estradiol.These increases should be considered when selecting an oral contraceptive for a woman taking atorvastatin calcium.

Warfarin:
atorvastatin calcium had no clinically significant effect on prothrombin time when administered to patients receiving chronic warfarin treatment.

Phamacokinetics:
Absorption:
Time for Maximum Plasma Concentration (Tmax) Oral: 1 to 2 hours
Bioavailability; Oral:
Absolute (atorvastatin): 14%
HMG-CoA reductase inhibitory activity: 30%

Effect of food:
Decreases the rate and extent of absorption by approximately 25% and 9%; respectively

Distribution:
Plasma Protein binding: 98% or greater
Volume of Distributor (Vd): 381 L

Metabolism:
Hepatic: Extensively metabolized through hydroxylation and beta-oxidation; does not undergo enterohepatic recirculation
Ortho-and parahydroxylated derivatives: Active; equivalent HMG-CoA reductase inhibitory activity to atorvastatin
Substrate of CYP3A4

Excretion:
Bile: Primary
Renal: Less than 2%

Dialyzable:
Hemodialysis: No
Peritoneal dialysis: No

Elimination:
Normally: 14 hours
Elderly: 19 hours
Hemodialysis: 11.8 to 14.7 hours

HMG-CoA reductase inhibitory activity:
20 to 30 hours

Ortho-hydroxy-atorvastatin (o-OH-atorvastatin):
Healthy subjects:
(40 mg): 23.6 hours
(80 mg): 32.1 hours

Hemodialysis:
(40 mg): 22.3 hours
(80 mg): 19 hours

Precaution:
Concomitant Medical Conditions:
Temporarily withhold or discontinue therapy when conditions that predispose patients to rhabdomyolysis and renal failure (e.g..; sepsis; hypotension; trauma; major surgery; uncontrolled seizures; and severe metabolic; endocrine and electrolyte disorders) are present.

Concomitant Use:
Avoid

use of

cyclosporine; gemfibrozil; telaprevir; and tipranavir/ritonavir

Elderly:

Use

caution in patients 65 years or older due to increased risk of myopathy and rhabdomyolysis.

Endocrine and Metabolic:
Uncontrolled hypothyroidism increases risk of myopathy and rhabdomyolysis
Increased HbA1c and serum glucose levels have been reported.

Hepatic:
Liver failure; with some fatal cases; has been reported; interrupt treatment if serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs; do not restart therapy if cause not identified
History of liver disease increases risk of liver dysfunction
Increases in serum transaminase levels greater than 3 times the ULN have been reported; monitoring recommended and discontinuation may be required if increased levels persist
Heavy alcohol use increases risk of liver dysfunction.

Immunologic:
Immune-mediated necrotizing myopathy; an autoimmune myopathy; has been reported; discontinue immediately if myopathy diagnosed or suspected.

Musculoskeletal:
Markedly elevated creatine phosphokinase (CPK) levels have been reported; discontinuation may be warranted
Myopathy and rhabdomyolysis with acute renal failure have been reported; especially with

higher doses

or concomitant use of cyclosporine or strong CYP3A4 inhibitors; monitoring recommended and discontinue immediately if myopathy diagnosed or suspected.

Neurologic:
Hemorrhagic stroke has been reported with greater incidence following stroke or transient ischemic attack (TIA) without cardiovascular disease within preceding 6 months Use caution in patients with preexisting amyotrophic lateral sclerosis (ALS) as rate of ALS functional decline may increase.

Renal:
Use caution in patients with history of renal impairment due to increased risk of myopathy

Pregnancy Category:
X (FDA)
D (AUS)

Breast Feeding:
Infant Risk has been demonstrated.

Monitoring:

Lipid panel; 2 to 4 weeks after initiation of atorvastatin and 2 to 4 weeks after dosage adjustment Liver function; baseline and as clinically warranted
Serum creatine kinase; although such monitoring may not prevent myopathy; patients who warrant closer monitoring are those with renal insufficiency usually as a consequence of long-standing diabetes mellitus

How To Take Or Administration:
Oral:
May be taken at any time of the day with or without food

Dosage Form:
Oral

Tablet

:
10mg
20mg
40mg
80mg

Treatment:
MANAGEMENT MILD TO MODERATE TOXICITY:
Treatment is symptomatic and supportive. Correct any significant fluid and/or electrolyte abnormalities in patients with vomiting or diarrhea.

MANAGEMENT OF SEVERE TOXICITY:

Treatment is symptomatic and supportive. Severe toxicity is not expected after an

overdose

.

Toxicology:
ADULTS:
LOVASTATIN:

Single doses

up to 200 mg of lovastatin have been well tolerated without significant adverse effects in adult human volunteers.

Overdoses

of up to 5 to 6 grams of lovastatin have been well tolerated; no specific symptoms occurred.

SIMVASTATIN:
The maximum reported

dose of simvastatin

ingestion is 3.6 g with no specific symptoms; recovery was complete without sequelae.

CHILDREN:
FLUVASTATIN:
Two children (a 2-year-old and a 3-year-old) ingested up to 80 mg of fluvastatin. Vomiting was induced in the children; and no capsules were present in emesis; both children recovered without any adverse effects.

Patient Counselling Or Clinical Teaching:
Instruct patient to report signs-symptoms of myopathy or rhabdomyolysis (muscle pain; tenderness; weakness; fever)
Drug may cause diarrhea; UTIs; extremity pain; nasopharyngitis; arthralgia; dyspepsia; or nausea
Advise patient to immediately report signs-symptoms of myopathy including unexplained muscle pain; tenderness; or weakness especially when accompanied by fever or malaise; or if symptoms persist after discontinuation of drug
Counsel patients to report signs-symptoms of liver injury (jaundice; dark urine; upper abdominal discomfort; anorexia; fatigue)
Counsel patient to avoid excessive quantities of alcohol to reduce risk of hepatotoxicity Instruct patient not to eat large amounts of grapefruit or drink more than 1 L-day of grapefruit juice with this drug

Neomycin (Dosing, Interaction, Side Effect, Administration, Etc..)

DRUG CLASS:
Aminoglycoside
Antibacterial
Antibiotic

DOSING:

Adult Dose

:
Hepatic encephalopathy:
4 to 12 g/day ORALLY in divided doses for 5 to 6 days; maximum 12 g/day; do not

use

longer than 2 weeks

Infection of skin; In minor cuts; scrapes; and burns; Prophylaxis:
Apply small amount TOPICALLY to affected area not more than 2 to 3 times daily; may be covered with a sterile bandage

Preparation of bowel for procedure; Preoperative; Adjunct:
1 g ORALLY 19; 18; and 9 hours prior to surgery in combination with recommended bowel preparation regimen which includes erythromycin

Pediatric Dose

:
Infection of skin; in minor cuts; scrapes; and burns; Prophylaxis:
Apply small amount TOPICALLY to affected area not more than 2 to 3 times daily; may be covered with a sterile bandage

INDICATIONS:
FDA-LABELED INDICATIONS:
Hepatic encephalopathy
Infection of skin; in minor cuts; scrapes; and burns; Prophylaxis
Preparation of bowel for procedure; Preoperative; Adjunct

NON-FDA LABELED INDICATIONS:
Eczema
Skin grafting

MECHANISM OF ACTION:

Neomycin sulfate

is an aminoglycoside antibiotic that exerts its bactericidal effect by inhibiting protein synthesis in susceptible bacterial cells. It is effective against gram-negative bacilli and some strains of gram-positive microorganisms; but ineffective against anaerobic bowel flora.

ADVERSE EFFECT:
Common:
Gastrointestinal:
Diarrhea
Nausea
Vomiting

Serious:
Otic:
Ototoxicity

Renal:
Nephrotoxicity

Respiratory:
Respiratory tract paralysis

CONTRAINDICATION:
Hypersensitivity to neomycin/aminoglycosides
Inflammatory/ulcerative gastrointestinal disease
Intestinal obstruction

DRUG INTERATION:
Caution should be taken in concurrent or serial

use of other neurotoxic

and/or nephrotoxic drugs because of possible enhancement of the nephrotoxicity and/or ototoxicity of

neomycin

Caution should also be taken in concurrent or serial

use of other aminoglycosides

and polymyxins because they may enhance neomycin's nephrotoxicity and/or ototoxicity and

potentiate neomycin

's neuromuscular blocking effects.

Oral neomycin

inhibits the gastrointestinal absorption of penicillin V, oral vitamin B-12, methotrexate and 5-fluorourcil. The gastrointestinal absorption of digoxin also appears to be inhibited. Therefore, digoxin serum levels should be monitored.
Oral neomycin may enhance the effect of coumarin in anticoagulants by decreasing vitamin K availability.

Major:
Alcuronium (probable)
Atracurium (probable)
Cidofovir (theoretical)
Cisatracurium (probable)
Colistimethate Sodium (theoretical)
Decamethonium (probable)
Doxacurium (probable)
Ethacrynic Acid (theoretical)
Fazadinium (probable)
Foscarnet (theoretical)
Furosemide (theoretical)
Gallamine (probable)
Hexafluorenium (probable)
Metocurine (probable)
Mivacurium (probable)
Pancuronium (probable)
Pipecuronium (probable)
Rapacuronium (probable)
Rocuronium (probable)
Sorafenib (theoretical)
Tubocurarine (probable)
Vecuronium (probable)

Moderate:
Bumetanide(Probable)
Digoxin (Probable)

PHAMACOKINETICS:
Absorption:
Poor absorbed

Distribution:
Plasma Protein binding: 0% to 30%

Excretion:
Fecal: approximately 97% (unabsorbed drug) as unchanged
Renal: small fraction; primary site
Dialyzable: yes (hemodialysis)

PRECAUSION:
Pre-existing renal; vestibular; or auditory impairment
Concomitant anesthesia or neuromuscular blockers; risk for neuromuscular blockade; respiratory paralysis
Concomitant neurotoxic; ototoxic; or nephrotoxic drugs; age (very young/very old) and dehydration; risk factors for toxicity

PREGNENCY CATEGORY:
D (FDA)
D (AUS)

BREAST FEEDING:
Infant Risk cannot be ruled out

MONITORING:
Improvement in neurologic function may indicate efficacy
Reduction in serum ammonia levels may indicate efficacy
Renal function; especially in high-risk patients; at baseline and periodically
Urinalysis for proteinuria; decreased specific gravity and casts and cells in urine; at baseline and periodically
Perform urinalysis to identify increased excretion of protein; specific gravity; casts and cells; at baseline and periodically during therapy

Neomycin serum concentrations

to avoid toxic levels
Serial vestibular and audiometric tests; especially in high-risk patients; even after drug withdrawal
Signs and symptoms of neurotoxicity; even after drug withdrawal
Vestibulocochlear nerve (8th cranial nerve) function; at baseline and periodically

DOSAGE FORM:
Oral Tablet:
500mg

Oral solution:
125mg/5ml

TREATMENTS:
MANAGEMENT OF TOXICITY:
Treatment is symptomatic and supportive. Maintain good urine output (3 to 6 mL/kg/hr) with IV fluids. For mild allergic reactions; treat with antihistamines; if severe; airway management; epinephrine; ECG monitoring; IV fluids.

TOXICOLOGY:
Nephrotoxicity may occur from gentamicin with persistent peak serum concentrations of more than 12 mcg/mL or trough concentrations more than 2 mcg/mL. Nephrotoxicity may occur from amikacin peak concentrations persistently greater than 20 to 35 mcg/mL and trough concentrations greater than 8 mcg/mL. The amount of aminoglycoside present in ophthalmic drops or ointments; otic preparations; or topical formulations do not cause systemic toxicity after ingestion.

PATIENT COUNSELING OR CLINICAL TEACHING:
This drug may cause diarrhea; nausea; and vomiting
Instruct patients receiving oral preparations to report signs/symptoms of neurotoxicity; ototoxicity; or nephrotoxicity
Patients receiving oral preparations should report signs/symptoms of respiratory tract paralysis. Patients who have recently received anesthesia are at a higher risk for this adverse effect
Tell patient to maintain adequate hydration to decrease the risk of toxicity
Advise patient there are multiple significant drug-drug interactions for this drug. Consult healthcare professional prior to new drug use (including over-the-counter and herbal drugs)

Pantoprazole (Dosing, Interaction, Side Effect, Administration, Etc..)

DRUG CLASS:
Gastric Acid Secretion Inhibitor
Proton Pump Inhibitor

DOSING:
Adult Dose:
Important Note:
Beers Criteria: Use caution or avoid use as potentially inappropriate in older adults.

Drug-induced gastrointestinal disturbance; Prophylaxis - Non-steroidal anti-inflammatory drug adverse reaction:
20 to 40 mg orally once daily for 6 months (off-label dosage)

Duodenal ulcer disease:
40 to 80 mg orally once daily for 4 to 8 weeks (

study dosage

)
40 mg IV once daily over 2 to 15 minutes for 6 days; 20 mg OR 80 mg was used in a few patients (study dosage)

Erosive esophagitis; Maintenance therapy - Gastroesophageal reflux disease:
40 mg orally once daily

Erosive esophagitis – Gastroesophageal reflux disease:
40 mg orally once daily for up to 8 weeks; if not healed; an additional 8-week course may be initiated
40 mg IV infusion once daily for 7 to 10 days

Gastric hypersecretion; Pathological:
Initial; 40 mg orally twice daily; titrate to patient response; doses up to 240 mg daily and over 2 years duration have been administered
80 mg IV infusion every 12 hours; can increase to every 8 hours; doses up to 240 mg/day and up to 6 days duration have been studied.

Gastroesophageal reflux disease:
Mild: 20 mg orally once daily for 8 weeks (study dosage).

Helicobacter pylori gastrointestinal tract infection:
(

Guideline Dosage

):
Clarithromycin triple regimen:
40 to 80 mg orally twice daily in combination with clarithromycin 500 mg orally twice daily and either amoxicillin 1 g orally twice daily or metronidazole 500 mg orally 3 times per day; continue regimen for 14 days

Bismuth quadruple regimen:
40 mg orally twice daily in combination with tetracycline 500 mg orally 4 times per day; metronidazole 250 mg orally 4 times per day or 500 mg orally 3 or 4 times per day; and either bismuth subcitrate 120 to 300 mg orally 4 times per day or bismuth subsalicylate 300 mg orally 4 times per day; continue regimen for 10 to 14 days

Concomitant regimen:
40 mg orally twice daily in combination with amoxicillin 1 g orally twice daily; clarithromycin 500 mg orally twice daily; and metronidazole or tinidazole 500 mg orally twice daily; continue regimen for 10 to 14 days

Sequential regimen:
40 mg orally twice daily plus amoxicillin 1 g orally twice daily for 5 to 7 days; then follow with clarithromycin 500 mg twice daily; metronidazole or tinidazole 500 mg twice daily; and

pantoprazole 40 mg

twice daily for 5 to 7 days

Hybrid regimen:
40 mg orally twice daily plus amoxicillin 1 g orally twice daily for 7 days; then follow with amoxicillin 1 g twice daily; clarithromycin 500 mg twice daily; metronidazole or tinidazole 500 mg twice daily; and

pantoprazole 40 mg twice daily

for 7 days

Levofloxacin triple regimen:
40 mg orally twice daily in combination with amoxicillin 1 g orally twice daily and levofloxacin 500 mg orally once daily; continue regimen for 10 to 14 days

Levofloxacin sequential regimen:
40 to 80 mg orally twice daily plus amoxicillin 1 g orally twice daily for 5 to 7 days; then follow with amoxicillin 1 g orally twice daily; metronidazole or tinidazole 500 mg orally twice daily;

pantoprazole 40 mg orally twice daily

; and levofloxacin 500 mg orally once daily for 5 to 7 days

LOAD regimen:
80 mg orally once daily in combination with levofloxacin 250 mg orally once daily; doxycycline 100 mg orally once daily; and nitazoxanide 500 mg twice daily; continue regimen for 7 to 10 days.

Recurrent gastrointestinal bleeding; Prophylaxis:
80 mg IV bolus followed by 8 mg/hour IV for 72 hours (study dosage).

Zollinger-Ellison syndrome:
80 mg IV infusion every 12 hours; can increase to every 8 hours; doses up to 240 mg/day and up to 6 day duration has been studied
Initial; 40 mg orally twice daily; titrate to patient response; doses up to 240 mg daily and over 2 years duration have been administered.

Pediatric Dose:
Important Note:
Beers Criteria: Use caution or avoid use as potentially inappropriate in older adults.

General Dosage Information:
Safety and efficacy not established in children.

Erosive esophagitis - Gastroesophageal reflux disease:
(5 years and older; 15 to less than 40 kg)
20 mg orally once daily for up to 8 weeks

(5 years and older; 40 kg and greater)
40 mg orally once daily for up to 8 weeks

Gastroesophageal reflux disease:
(5 to 11 years)
Initial; 20 mg (0.6 to 0.9 mg/kg) orally once daily; increase to 40 mg once daily (1.2 mg/kg or greater) if symptoms do not improve (study dosage).







MECHANISM OF ACTION:

Pantoprazole sodium

is a proton pump inhibitor (PPI) that covalently binds to the (H(+); K(+))-ATPase enzyme system at the secretory surface of the gastric parietal cell. This action suppresses the final step in gastric acid production and leads to inhibition of both basal and stimulated acid secretion

INDICATIONS:
FDA-LABELED INDICATIONS:
Erosive esophagitis; Maintenance therapy - Gastroesophageal reflux disease
Erosive esophagitis - Gastroesophageal reflux disease
Gastric hypersecretion; Pathological
Zollinger-Ellison syndrome

NON-FDA LABELED INDICATIONS:
Drug-induced gastrointestinal disturbance; Prophylaxis - Non-steroidal anti-inflammatory drug adverse reaction
Duodenal ulcer disease
Gastroesophageal reflux disease
Helicobacter pylori gastrointestinal tract infection
Recurrent gastrointestinal bleeding; Prophylaxis

ADVERSE EFFECT:
Common:
Gastrointestinal:
Abdominal pain (3%)
Diarrhea (4%)
Flatulence (4%)

Neurologic:
Headache (5%)

Serious:
Dermatologic:
Cutaneous lupus erythematosus.

Gastrointestinal:
Atrophic gastritis
Clostridium difficile diarrhea

Hematologic:
Thrombocytopenia (less than 1%)

Immunologic:
Stevens-Johnson syndrome
Toxic epidermal necrolysis

Musculoskeletal:
Disorder of muscle
Fracture of bone
Osteoporosis-related
Hip fracture
Rhabdomyolysis

Renal:
Interstitial nephritis

CONTRAINDICATION:
Rilpivirine(theoretical)

DRUG INTERACTION:
Antiretrovirals:
The effect of PPIs on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known.
Decreased exposure of some antiretroviral drugs (e.g., rilpivirine atazanavir, and nelfinavir) when used concomitantly with

pantoprazole

may reduce antiviral effect and promote the development of drug resistance.
Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with pantoprazole may increase toxicity

Warfarin:
Increased INR and prothrombin time in patients receiving PPIs, including

pantoprazole sodium

, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death.

Methotrexate:
Concomitant

use of pantoprazole sodium

with methotrexate (primarily at high dose) may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of high-dose methotrexate with PPIs have been conducted.

Drugs Dependent on Gastric pH for Absorption (e.g., iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole)

Pantoprazole sodium

can reduce the absorption of other drugs due to its effect on reducing intragastric acidity

False Positive Urine Tests for THC:
There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs, including pantoprazole.

Major:
Acalabrutinib (probable)
Atazanavir (theoretical)
Bosutinib (theoretical)
Capecitabine (probable)
Cilostazol (theoretical)
Citalopram (theoretical)
Dasatinib (theoretical)
Erlotinib (probable)
Eslicarbazepine Acetate (theoretical)
Gefitinib (theoretical)
Ketoconazole (theoretical)
Ledipasvir (theoretical)
Methotrexate (probable)
Mycophenolate Mofetil (probable)
Nelfinavir (probable)
Neratinib (probable)
Nilotinib (theoretical)
Pazopanib (established)
Saquinavir (theoretical)
Secretin Human (theoretical)
Sunitinib (probable)
Velpatasvir (theoretical)
Vismodegib (theoretical)

Moderate:
Levothyroxin(Probable)
Warfarin(Probable)

PHARMACOKINETICS:
Absorption:
ORAL;

DELAYED RELEASE TABLETS

:
Bioavailability: Approximately 77%

Effect of food:
Food may delay its absorption up to 2 hours or longer
With high fat meal: Cmax and AUC decreased by 51% and 29%

Time for Maximum Plasma Concentration (Tmax):
2.5 hr
1.5 to 2 hours (Pediatrics)
ORAL; FOR-DELAYED-RELEASE SUSPENSION:
Effect of food: Administer 30 minutes before a meal
Time for Maximum Plasma Concentration (Tmax): 2 to 2.5 hours

Distribution:
Plasma Protein binding: about 98% to primarily albumin

Volume of Distribution (Vd):
Extensive metabolizers (IV): approximately 11 L to 23.6 L
Pediatrics (oral): 0.21 to 0.43 L/kg

Metabolism:
Hepatic:
Cytochrome P450 CYP2C19
Minor metabolism from CYP3A4; 2D6; and 2C9

Excretion:
Fecal: (oral or IV; normal metabolizers); 18%
Renal: (oral or IV; normal metabolizers); approximately 71%; none as unchanged
Dialyzable: no (hemodialysis)

Total body clearance:
IV: 7.6 to 14 L/hour
Oral; Pediatrics: 0.18 to 2.08 L/hr/kg

Elimination:
Oral or IV: 1 hour
Oral or IV: Slow metabolizers; 3.5 to 10 hours
Pediatrics: 0.7 to 5.34 hours

PRECAUTION:
Beers Criteria:
Avoid scheduled

use of proton pump inhibitors

for longer than 8 weeks in older adults; due to risk of Clostridium difficile infection and bone loss and fractures; unless needed for high-risk patients (e.g.; oral corticosteroids; chronic NSAID use); erosive esophagitis; Barrett esophagitis; pathological hypersecretory condition; or need for maintenance treatment (e.g.; due to failure of drug discontinuation or histamine-2 blockers).

Dermatologic:
New or worsening cutaneous lupus erythematosus has been reported within weeks to years after continuous drug therapy; avoid using for longer than medically indicated and discontinue use if suspected.

Endocrine and metabolic:
Hypomagnesemia has been reported in patients treated with proton pump inhibitors for at least 3 months; tetany; arrhythmias; and seizures may occur; monitoring recommended with

prolonged use

or concomitant drugs that may cause hypomagnesemia; discontinuation may be required.

Predisposition to zinc deficiency; consider zinc supplementation when treated with IV pantoprazole; use caution with coadministration of other IV EDTA-containing products.

Vitamin B12 deficiency may occur with prolonged use (eg greater than 1 to 2 years); monitoring recommended.

Gastrointestinal:
Symptomatic response does not preclude gastric malignancy
Clostridium difficile-associated diarrhea may occur; especially in hospitalized patients;

use lowest dose

and shortest treatment duration.

Hematologic:
Thrombophlebitis has been reported with IV administration.

Hepatic:
Mild; transient transaminase elevations have been reported with IV administration.

Immunologic:
Anaphylaxis and other serious reactions; including erythema multiforme; Stevens-Johnson syndrome; and toxic epidermal necrolysis have been reported with IV administration.

New or worsening systemic lupus erythematosus has been reported within weeks to years of treatment initiation; avoid using for longer than medically indicated and discontinue use if suspected.
Lab interference:
Gastric acid suppression may increase serum chromogranin A (CgA) levels; withhold pantoprazole for 14 days prior to CgA testing neuroendocrine tumor assessment.

Musculoskeletal:

Osteoporosis-related bone fracture of hip; wrist; or spine may occur; especially with higher (multiple daily) doses or longer duration of therapy (1 year or longer); use lowest dose and shortest treatment duration.
Renal: Acute interstitial nephritis; typically associated with idiopathic hypersensitivity; has been reported; discontinuation required Concomitant use: Use with atazanavir or nelfinavir not recommended.

PREGNANCY CATEGORY:
B (FDA)
B3 (AUS)

BREAST FEEDING:
Infant Risk cannot be ruled out

MONITORING:
GERD:
Decreased abdominal and gastroesophageal discomfort may indicate efficacy

Peptic ulcer:
Endoscopic improvement may indicate efficacy
Negative urea breath (UB) test 4 to 6 weeks after completion of therapy

Serum magnesium:
Routine screening is not necessary; consider screening prior to initiation and periodically during prolonged therapy

Serum vitamin B12:
Although no routine screening is needed; may consider screening every 1 to 2 years for deficiency in patients receiving prolonged therapy.

HOW TO TAKE OR ADMINISTRATION:
General Information
Intravenous administration should be discontinued as soon as an oral route is possible
Parenteral routes other than the IV route are not recommended

Intravenous:
Administer through a dedicated line or through a Y-site; flush before and after administration with 5% dextrose injection, 0.9% sodium chloride injection, or Lactated Ringer's injection

Injection is NOT compatible with midazolam and may not be compatible with products containing zinc; compatible solutions include 5% Dextrose Injection, 0.9% Sodium Chloride Injection, or Lactated Ringer's Injection

(15-minute infusion) reconstitute the appropriate number of vials with 10 mL of 0.9% sodium chloride injection and then dilute to a total volume of 100 mL with 5% dextrose injection, 0.9% sodium chloride injection, or lactated Ringer's injection to a final concentration of approximately 0.4 mg/mL for a 40 mg dose and 0.8 mg/mL for an 80 mg dose; administer IV over a period of 15 minutes at a rate of approximately 7 mL/min

(2-minute infusion) reconstitute the appropriate number of vials with 10 mL of 0.9% sodium chloride injection for each vial to a final concentration of approximately 4 mg/mL; administer total volume IV over a period of at least 2 minutes
reconstituted and diluted solutions do not need to be protected from light

Nasogastric:
(Delayed release suspension)
Concomitant administration of antacids does not affect absorption

Remove plunger from the barrel of a 60 mL catheter tip syringe; connect catheter tip syringe to a 16 French (or larger) nasogastric tube; hold the syringe attached to the tubing as high as possible during process to prevent any bending of the tubing; empty granules into the barrel of syringe; add 10 mL of apple juice; gently tap and/or shake the barrel of the syringe; rinse and tap and/or shake again with apple juice; repeat with at least 2 additional 10 mL aliquots of apple juice; no granules should remain in the syringe

Oral:
(Delayed-release tablets)
Take with or without food; concomitant administration of antacids does not affect absorption
Swallow tablets whole, do not split, crush, or chew

(Delayed release suspension)
Sprinkle intact granules on 1 teaspoonful of applesauce or apple juice, swallow within 10 minutes of preparation and 30 minutes prior to a meal; rinse the container 1 or 2 times with apple juice and swallow to remove any remaining granules; do not chew or crush

DOSAGE FORM:
Intravenous Powder for Solution:
40 MG

Oral Tablet; Enteric Coated:
20 MG
40 MG.

TREATMENT:
MANAGEMENT OF MILD TO MODERATE TOXICITY:
Treatment is symptomatic and supportive. Correct any significant fluid and/or electrolyte abnormalities in patients with severe diarrhea and/or vomiting.

MANAGEMENT OF SEVERE TOXICITY:
Treatment is symptomatic and supportive. Significant toxicity is not expected after an overdose.

PATIENT COUNSELING OR CLINICAL TEACHING:
Counsel patient to report symptoms of cutaneous or systemic lupus erythematosus
Advise patient that drug may increase risk for osteoporosis-related fractures of the hip; wrist; or spine with multiple daily doses that are continued for longer than a year
Warn patient to report diarrhea that does not improve; especially with persistent watery stools; fever; and abdominal pain

Oral side effects

may include abdominal pain; nausea; diarrhea; vomiting; flatulence; dizziness; headaches; fever; rash; and arthralgia
Injection

side effects

may include injection site reactions (e.g.; thrombophlebitis; abscess)
Tell patient to immediately report signs/symptoms of hypomagnesemia (e.g.; dizziness; palpitations; tetany; seizures.
Instruct patient using delayed-release oral suspension to mix with 1 teaspoonful of apple juice or applesauce and take at least 30 minutes before a meal
Counsel patient using nasogastric tube to mix delayed-release oral suspension with 2 teaspoonfuls of apple juice in syringe and take at least 30 minutes before a meal




Disclaimer:
For the Registered Medical Practitioner Only. We are not recommended for self medication. self medication is may harmful for health. We are only Provide information about medicine.

Pioglitazone (Dosing, Interaction, Side Effect, Administration, Etc..)

CLASS:
Antidiabetic
Thiazolidinedione

DOSING:

Adult Dose

:
Important Note:
Obtain liver function tests prior to initiation of therapy
Beers Criteria: Use caution or avoid use as potentially inappropriate in older adults

Type 2 diabetes mellitus:
Initial; 15 or 30 mg orally once daily; titrate in 15-mg increments; Maximum 45 mg daily

Pediatric Dose

:
Important Note:
Obtain liver function tests prior to initiation of therapy
Beers Criteria: Use caution or avoid use as potentially inappropriate in older adults

General Dosage Information:
Safety and effectiveness not established in pediatric patients; use is not recommended







MECHANISM OF ACTION:
Pioglitazone hydrochloride; a thiazolidinedione antidiabetic agent and a potent peroxisome proliferator-activated receptor-gamma (PPAR (gamma)) agonist; is dependent on the presence of insulin for its mechanism of action. It increases insulin-dependent glucose disposal and decreases hepatic glucose output by decreasing insulin resistance in the periphery and in the liver

ADVERSE EFFECT:
Common:
Cardiovascular:
Edema (4.8% to 15.3%)

Endocrine metabolic:
Weight increased

Hematologic:
Anemia (less than or equal to 2%)

Musculoskeletal:
Fracture of bone (5.1%)
Myalgia (5.4%)

Neurologic:
Headache (9.1%)

Respiratory:
Pharyngitis (5.1%)
Sinusitis (6.3%)
Upper respiratory infection (13.2%)

Serious:
Cardiovascular:
Congestive heart failure

Hepatic:
Alanine aminotransferase(ALT)/ Serum glutamic pyruvic transaminase (SGPT) level raised (0.3%)

Liver failure Ophthalmic:
Diabetic macular edema

Renal:
Bladder cancer (0.23% to 0.54%)

Respiratory:
Pneumonia

CONTRAINDICATION:
New York Heart Association Class III or IV heart failure
Hypersensitivity to

pioglitazone hydrochloride

or any other component of the product

INTERACTION:
Strong CYP2C8 Inhibitors:
An inhibitor of CYP2C8 (e.g.; gemfibrozil) significantly increases the exposure (area under the serum concentration-time curve or AUC) and half-life (t½) of

pioglitazone

. Therefore; the

maximum recommended dose of pioglitazone

is 15 mg daily if used in combination with gemfibrozil or other strong CYP2C8 inhibitors. Since the

minimum dose of pioglitazone

exceeds 15 mg; patients taking concomitant strong CYP2C8 inhibitors should switch to individual components of ; unless the prescribing health care provider determines that the benefit of clearly outweighs the risk of increased pioglitazone exposure

CYP2C8 Inducers:
An inducer of CYP2C8 (e.g.; rifampin) may significantly decrease the exposure (AUC) of pioglitazone. Therefore; if an inducer of CYP2C8 is started or stopped during treatment with pioglitazone; changes in diabetes treatment may be needed based on clinical response without exceeding the maximum recommended

daily dose of 45 mg for pioglitazone

Major:
Acarbose (theoretical)
Balofloxacin (theoretical)
Besifloxacin (theoretical)
Chlorpropamide (theoretical)
Ciprofloxacin (theoretical)
Enoxacin (theoretical)
Fleroxacin (theoretical)
Flumequine (theoretical)
Gatifloxacin (theoretical)
Gemifloxacin (theoretical)
Glimepiride (theoretical)
Glipizide (theoretical)
Glyburide (theoretical)
Ifosfamide (theoretical)
Insulin (theoretical)
Insulin Aspart; Recombinant (theoretical)
Insulin Bovine (theoretical)
Insulin Degludec (theoretical)
Insulin Detemir (theoretical)
Insulin Glargine; Recombinant (theoretical)
Insulin Glulisine (theoretical)
Insulin Lispro; Recombinant (theoretical)
Lanreotide (theoretical)
Levofloxacin (theoretical)
Lomefloxacin (theoretical)
Metformin (theoretical)
Moxifloxacin (theoretical)
Nadifloxacin (theoretical)
Nateglinide (theoretical)
Nifedipine (probable)
Norfloxacin (theoretical)
Octreotide (theoretical)
Ofloxacin (theoretical)
Pasireotide (theoretical)
Pazufloxacin (theoretical)
Pefloxacin (theoretical)
Piperaquine (theoretical)
Pixantrone (theoretical)
Prulifloxacin (theoretical)
Repaglinide (theoretical)
Rufloxacin (theoretical)
Sparfloxacin (theoretical)
Thioctic Acid (theoretical)
Tolazamide (theoretical)
Tolbutamide (theoretical)
Tolvaptan (theoretical)
Tosufloxacin (theoretical)

Moderate:
Acebutolol (probable)
Atenolol (probable)
Atorvastatin (probable)
Betaxolol (probable)
Bisoprolol (probable)
Bitter Melon (probable)
Carteolol (probable)
arvedilol (probable)
Celiprolol (probable)
Clopidogrel (probable)
Esmolol (probable)
Fenugreek (probable)
Glucomannan (probable)
Guar Gum (probable)
Ketoconazole (probable)
Labetalol (probable)
Levobunolol (probable)
Metipranolol (probable)
Metoprolol (probable)
Nadolol (probable)
Nebivolol (probable)
Nilotinib (probable)
Oxprenolol (probable)
Penbutolol (probable)
Pindolol (probable)
Practolol (probable)
Propranolol (probable)
Psyllium (probable)
Rifampin (established)
Sotalol (probable)
Timolol (probable)
Topiramate (probable)

PHARMACOKINETICS:
Absorption:
Time for Maximum Plasma Concentration (Tmax):
Oral: Within 2 hours

Effects of food:
Increase in Tmax to 3 to 4 hours

Distribution:
Volume of Distribution (Vd): 0.63 L/kg
Plasma Protein binding: Greater than 99%

Metabolism:
Metabolised by Hydroxylation and oxidation
Extrahepatic: Some
M-III (major): Active
M-IV (major): Active
CYP2C8 substrate

Excretion:
Renal excretion: 15% to 30%
Biliary excretion: Extensive; as changed and unchanged drug
Total body clearance: 5 to 7 L/hr

Elimination:
Oral: 3 to 7 hours
Geriatric: 10 hours
M-III and M-IV metabolites: 16 to 24 hours

PRECAUTION:
Beers Criteria:
Avoid

use in older adults

with heart failure due to risk of fluid retention and heart failure exacerbation

Cardiovascular:
New or worsening dose-related edema and fluid retention have been reported; use caution in patients with edema or at risk for congestive heart failure. Monitoring recommended

Endocrine and metabolic:
Concomitant

use with insulin

or other antidiabetic medications (especially insulin secretagogues such as sulfonylureas) may increase the risk for hypoglycemia

Hepatic:
Hepatic failure; including fatal cases; has been reported; screening and monitoring recommended. Interruption of therapy required for abnormal liver tests; do not restart therapy if serum ALT greater than 3 times the ULN and no other cause is identified

Musculoskeletal:
Increased risk of bone fracture in female patients; especially in the distal upper limb (forearm; hand; or wrist) or distal lower limb (foot; ankle; fibula; and tibia)

Ophthalmic:
Macular edema has been reported

Renal:
Use not recommended in patients with active bladder cancer. Weigh benefits versus risk in patients with a prior history of bladder cancer as use may increase risk of urinary bladder tumors

Prolonged use

(more than 12 months) and/or high

cumulative doses

; increased risk of bladder cancer

PREGNANCY CATEGORY:
Fetal Risk cannot be ruled out

BREAST FEEDING:
Infant Risk cannot be ruled out

MONITORING:
Achieving glycemic control; including meeting HbA1c goal is indicative of efficacy
HbA1c; twice yearly in patients who are meeting treatment goals; every 3 months in patients whose therapy has changed and/or who are not meeting glycemic goals; more frequently as clinically warranted
Blood glucose (self-monitoring); as needed to assist in meeting goals of therapy
Liver function tests; prior to initiating therapy and promptly in any patient who reports symptoms of liver injury (fatigue; anorexia; right upper abdominal discomfort; dark urine; or jaundice)
Signs and symptoms of congestive heart failure and fluid retention (excessive or rapid weight gain; dyspnea; or edema); following initiation and after any dose increase
Bone health; particularly in female patients; according to current standards of care during treatment

HOW TO TAKE OR ADMINISTRATION:
Oral:
Give without regard to meals

DOSAGE FORM:
Oral

Tablet

:
15mg
30mg
45mg

TREATMENTS:
MANAGEMENT OF MILD TO MODERATE TOXICITY:
Symptomatic and supportive care is the mainstay of treatment in patients who present with mild to moderate thiazolidinedione toxicity. If hypoglycemia develops, coingestion of other hypoglycemic agents should be considered. Hypoglycemia with thiazolidinediones is uncommon, but they are often prescribed with other antidiabetic agents that can produce hypoglycemia. A 4 to 6 hour observation period is reasonable.

MANAGEMENT OF SEVERE TOXICITY:
Early positive pressure ventilation/intubation should be performed if the patient presents with pulmonary edema. Consider diuresis in massive fluid overload. Adequate circulatory support with IV fluids and vasopressors (if needed) should be assured if a patient presents with circulatory collapse.

TOXICOLOGY:
TOXICITY:
The

minimum toxic dose

for thiazolidinediones is not well established.

PIOGLITAZONE:
An adult denied any clinical symptoms after taking up to 120 mg/day of pioglitazone for 4 days and then 180 mg/day for 7 days.

PATIENT COUNSELING OR CLINICAL TEACHING:
Advise patient to report symptoms of congestive heart failure
Advise patient to report symptoms of hepatoxicity
Warn premenopausal anovulatory women that ovulation and subsequent pregnancy may occur

Side effects

may include headaches; myalgia; pharyngitis; sinusitis; upper respiratory tract infections; edema; and weight increase
Advise patient to report symptoms of bladder cancer
Advise patient to report symptoms of macular edema


Click Here For Download PDF File of Piogliptazone Hydrochloride


Disclaimer:
For the Registered Medical Practitioner Only. We are not recommended for self medication. self medication is may harmful for health. We are only Provide information about medicine.

Vitamin D (Dosing, Interaction, Side Effect, Administration, Etc..)

DRUG CLASS:
Nutriceutical
Nutritive Agent

Vitamin D

DOSING:
Adult Dose:
Falls; Prophylaxis:
51 to 70 years:
600 international units/day is recommended for at-risk patients

Older than 70 years:
800 international units/day is recommended for at-risk patients

Familial x-linked hypophosphatemic vitamin D refractory rickets:
12000 to 500000 international units ORALLY daily

Hypoparathyroidism:
50000 to 200000 international units ORALLY once daily (plus calcium lactate 4 g 6 times daily)

Vitamin D deficiency

(NON-FDA LABELED INDICATION):
50000 international units ORALLY every week for 8 to 12 weeks; may repeat another 8 to 12 weeks if 25-hydroxyvitamin D levels are less than 30 nanograms/milliliter (ng/mL)

(Malabsorption syndrome)
50000 international units ORALLY every day or every other day

(Granulomatous disorders and some lymphomas)
50000 international units ORALLY once a week for 4 weeks or every 2 to 4 weeks; maintain 25-hydroxyvitamin D levels between 20 and 30 ng/mL
(Nephrotic syndrome) 50000 international units ORALLY twice a week for 8 to 12 weeks; may repeat another 8 to 12 weeks if 25-hydroxyvitamin D levels are less than 30 ng/mL

(Chronic kidney disease stage 3 or 4; 25-hydroxyvitamin D levels less than 5 ng/mL)
50000 international units ORALLY every week for 12 weeks; then monthly for 6 months

(Chronic kidney disease stage 3 or 4; 25-hydroxyvitamin D levels between 5 and 15 ng/mL)
50000 international units ORALLY weekly for 4 weeks; then monthly for 6 months

(Chronic kidney disease stage 3 or 4; 25-hydroxyvitamin D levels between 16 and 30 ng/mL)
50000 international units ORALLY monthly for 6 months

(Chronic kidney disease stage 5)
50000 international units ORALLY weekly for 24 weeks

Vitamin D deficiency

; Prophylaxis:
200 international units/day; ages 50 to 70; 400 international units/day; over age 70; 600 international units/day

Pediatric Dose:
Familial x-linked hypophosphatemic vitamin D refractory rickets:
12000 to 500000 international units ORALLY daily;

dosage

must be individualized
(neonatal) initial; 2000 to 4000 international units ORALLY once daily for 6 to 12 weeks; then 200 to 400 international units/day

Hypoparathyroidism:
50000 to 200;000 international units ORALLY once daily (plus calcium lactate 4 g 6 times daily);

dosage

must be individualized

Vitamin D deficiency

; Prophylaxis:
Total daily intake requirement of at least 400 international units/day beginning first few days of life to maintain serum 25-hydroxyvitamin D serum concentrations at 50 nmol/L or greater (20 nanograms/milliliter or greater)

MECHANISM OF ACTION:
Ergocalciferol; or vitamin D(2); promotes active absorption of calcium and phosphorus; thus increasing serum calcium and phosphate levels sufficiently to allow bone mineralization. It also mobilizes calcium and phosphate from bone and increases the reabsorption of calcium and phosphate by the renal tubules.

ADVERSE EFFECT:
Common:
Gastrointestinal:
Constipation
Loss of appetite
Nausea

Serious:
Endocrine metabolic:
Hypercalcemia
Hypervitaminosis D

CONTRAINDICATION:
Abnormal sensitivity to the toxic

effects of vitamin D

Hypercalcemia
Hypervitaminosis D
Malabsorption syndrome

DRUG INTERACTION:
Contraindicated:
Burosumab-twza(Theoritical)

PHARMACOKINETICS:
Metabolism:
Hepatic and Renal; hydroxylation
Metabolites: 25-hydroxyvitamin D and 1;25-dihydroxyvitamin D

Excretion:
Dialyzable:Yes

PRECAUTION:
Adequate dietary calcium; necessary for clinical response to

vitamin D therapy

Evaluate

vitamin D intake

from fortified foods;

dietary supplements

; and self-administered and prescription drug sources
Hyperphosphatemia may occur; must maintain normal serum phosphorus levels by aluminum gel administration and/or dietary phosphate restriction to prevent metastatic calcification

Hypersensitivity to vitamin D

; particularly in infants with idiopathic hypercalcemia
hypoparathyroidism; dihydrotachysterol; intravenous calcium; and/or parathyroid hormone may be required during treatment
Tartrazine (FD&C Yellow No. 5) sensitivity; increased risk of allergic reactions including bronchial asthma in susceptible patients; especially in patients with concomitant aspirin sensitivity
Vitamin D-resistant rickets; the range between therapeutic and toxic doses is narrow

PREGNENCY CATEGORY:
C (FDA)

BREAST FEEDING:
AAP: Maternal medication usually compatible with breastfeeding
WHO: Compatible with breastfeeding

MONITORING:
Serum calcium, serum phosphorus; every 2 wk or more frequently
Bone X-ray; monthly

DOSAGE FORM:
Oral Capsule:
2000 IU
50000 IU

Oral Capsule; Liquid Filled:
50000 IU

Oral Solution:
8000 IU/1 ML
400 IU/0.05 ML

Oral Tablet:
400 IU
2000 IU

TREATMENTS:
MILD TO MODERATE TOXICITY:
Monitor serum calcium and phosphorus concentrations. Discontinue

all vitamin D

and

calcium supplements

; start a low-calcium diet. Increase oral fluids or IV fluids, if patient is unable to tolerate fluids, to increase renal calcium clearance. Diuresis with IV 0.9% NaCl and furosemide can be used to promote calcium excretion.

SEVERE TOXICITY: HYPERCALCEMIA:
Monitor serum calcium and phosphorus concentrations until levels have stabilized, discontinue

all supplements

. Administer IV 0.9% saline and furosemide to enhance calcium elimination. Corticosteroids: Hydrocortisone: 100 mg/day OR Prednisone: 20 mg/day can improve hypercalcemia and hypercalcuria. Bisphosphonates (eg, pamidronate 90 mg IV; alendronate) have been used successfully to treat severe hypercalcemia. Calcitonin has also been used. Hemodialysis may be indicated in patients with severe hypercalcemia that is unresponsive to other treatment. Cardiac dysrhythmias may develop, obtain a baseline ECG and continuous cardiac monitoring.

SEIZURES:
Treat initially with benzodiazepines, followed by barbiturates as needed.

OTHER:
Monitor CNS and renal function.

TOXICOLOGY:
TOXICITY: A specific toxic dose has not been established. Toxicity has been reported after Vitamin D intake of 50,000 to 150,000 International Units daily for prolonged periods. Two adults ingested

supplements

containing large doses (manufacturing error) of vitamin D (1,864,000 and 970,000 International Units

vitamin D3 daily

, respectively) daily for several months and developed significant toxicity and prolonged elevated concentrations of 5-hydroxyvitamin D for up to a year. However, no permanent sequelae developed. A 3-month-old inadvertently received 12000 International Units of vitamin D daily for approximately 20 days; a serum 25-hydroxyvitamin D level was elevated (422 ng/mL), but no symptoms developed. In a similar case, a 2-month-old received 12000 International Units of vitamin D for approximately 30 days; a serum 25-hydroxyvitamin D level was markedly increased (750 ng/mL) along with hypercalcemia. The infant recovered completely following supportive care. Two elderly patients developed no evidence of clinical effects after inadvertently receiving 2,000,000

International Units of Vitamin D3

.

PATIENT COUNSELING OR CLINICAL TEACHING:
Warn patient to report symptoms of hypercalcemia.
Side effects with excessive use may include nausea; anorexia; weight loss; constipation; polyuria; polydipsia; hypertension; weakness; and muscle aches or stiffness.
Instruct patient to maintain adequate intake of calcium with drug.
Advise patient to avoid additional

vitamin D supplements

.




Disclaimer:
For the Registered Medical Practitioner Only. We are not recommended for self medication. self medication is may harmful for health. We are only Provide information about medicine.

Rabeprazole (Dosing, Interaction, Side Effect, Administration, Etc..)

DRUG CLASS:
Gastrointestinal Agent
Proton Pump Inhibitor

DOSING:

Adult Dose

:
Important Note:
Beers Criteria: Use caution or

avoid use

as potentially inappropriate in older adults

Duodenal ulcer disease:
20 mg ORALLY once daily after the morning meal for up to 4 weeks
Duodenal ulcer disease; Triple therapy - Helicobacter pylori gastrointestinal tract infection:
20 mg orally twice daily in combination with amoxicillin 1000 mg twice daily and clarithromycin 500 mg twice daily for 7 days (FDA dosage)

Clarithromycin triple regimen; 20 to 40 mg orally twice daily in combination with clarithromycin 500 mg orally twice daily and either amoxicillin 1 g orally twice daily or metronidazole 500 mg orally 3 times per day; continue regimen for 14 days (guideline dosage)

Sequential regimen; 20 mg orally twice daily plus amoxicillin 1 g orally twice daily for 5 to 7 days; then follow with clarithromycin 500 mg twice daily; metronidazole or tinidazole 500 mg twice daily; and

rabeprazole 20 mg

twice daily for 5 to 7 days (guideline dosage)

Levofloxacin triple regimen; 20 mg orally twice daily in combination with amoxicillin 1 g orally twice daily and levofloxacin 500 mg orally once daily; continue regimen for 10 to 14 days (guideline dosage).

Gastric hypersecretion:
Initial; 60 mg ORALLY once daily; individualize dose to patient needs; doses up to 100 mg/day or 60 mg twice daily have been used.

Gastroesophageal reflux disease:
20 mg ORALLY once daily up to 4 weeks

Gastroesophageal reflux disease; Erosive or ulcerative:
20 mg ORALLY once daily for 4 to 8 weeks

Gastroesophageal reflux disease; Erosive or ulcerative; maintenance:
20 mg ORALLY once daily

Helicobacter pylori gastrointestinal tract infection - Peptic ulcer disease; Quadruple therapy:
Bismuth quadruple regimen:
20 mg orally twice daily in combination with tetracycline 500 mg orally 4 times per day; metronidazole 250 mg orally 4 times per day or 500 mg orally 3 or 4 times per day; and either bismuth subcitrate 120 to 300 mg orally 4 times per day or bismuth subsalicylate 300 mg orally 4 times per day; continue regimen for 10 to 14 days (guideline dosage)

Concomitant regimen:
20 mg orally twice daily in combination with amoxicillin 1 g orally twice daily; clarithromycin 500 mg orally twice daily; and metronidazole or tinidazole 500 mg orally twice daily; continue regimen for 10 to 14 days (guideline dosage)

Hybrid regimen:
20 mg orally twice daily plus amoxicillin 1 g orally twice daily for 7 days; then follow with amoxicillin 1 g twice daily; clarithromycin 500 mg twice daily; metronidazole or tinidazole 500 mg twice daily; and

rabeprazole 20 mg twice daily

for 7 days (guideline dosage)

Levofloxacin sequential regimen:
20 to 40 mg orally twice daily plus amoxicillin 1 g orally twice daily for 5 to 7 days; then follow with amoxicillin 1 g orally twice daily; metronidazole or tinidazole 500 mg orally twice daily;

rabeprazole

20 mg orally twice daily; and levofloxacin 500 mg orally once daily for 5 to 7 days (guideline dosage)

LOAD regimen:
40 mg orally once daily in combination with levofloxacin 250 mg orally once daily; doxycycline 100 mg orally once daily; and nitazoxanide 500 mg twice daily; continue regimen for 7 to 10 days (guideline dosage).

Pediatric Dose

:
Important Note:
Beers Criteria: Use caution or

avoid use

as potentially inappropriate in older adults.

General Dosage Information:
Safety and efficacy for treatment of GERD not established in pediatric patients younger than 1 year

Gastroesophageal reflux disease:
12 years or older:
20 mg ORALLY once daily up to 8 weeks

1 to 11 years:
15 kg or greater; 10 mg (

manufacturer dose

) to 20 mg (

study dose

) ORALLY once daily for up to 12 weeks

1 to 11 years:
less than 15 kg; 5 mg ORALLY once daily for up to 12 weeks; may increase to 10 mg ORALLY once daily if inadequate response.

INDICATIONS:
FDA-LABELED INDICATIONS:
Allergic conjunctivitis
Allergic rhinitis; Perennial and seasonal
Anaphylaxis; Adjunct
Dermatographic urticaria
Hypersensitivity reaction; To blood or plasma; or mild allergic skin manifestations

Urticaria due to cold
Vasomotor rhinitis

NON-FDA LABELED INDICATIONS:
Loss of appetite
Pruritus
Schizophrenia
Spasticity - Spinal cord injury





MECHANISM OF ACTION:

Rabeprazole sodium

is a gastric proton pump inhibitor that does not possess anticholinergic or histamine H(2)-receptor antagonist properties. It suppresses gastric acid secretion by inhibiting the gastric H+; K+-ATPase at the secretory surface of parietal cells

ADVERSE EFFECT:
Common:
Gastrointestinal:
Abdominal pain (3.6% to 5%)
Diarrhea (up to 5%)
Nausea (4.5%)
Vomiting (3.6%)

Neurologic:
Headache (up to 9.9%)
Serious:
Dermatologic:
Cutaneous lupus erythematosus
Erythema multiforme
Stevens-Johnson syndrome
Toxic epidermal necrolysis

Gastrointestinal:
Clostridium difficile diarrhea

Immunologic:
Anaphylaxis
Systemic lupus erythematosus

Musculoskeletal:
Fracture of bone
Rhabdomyolysis

Renal:
Interstitial nephritis
Acute

CONTRAINDICATION:
Concomitant use of rilpivirine-containing products
Hypersensitivity reactions; including anaphylaxis; anaphylactic shock; angioedema; bronchospasm; acute interstitial nephritis; and urticaria; to

rabeprazole

; substituted benzimidazoles; or any component of the product

DRUG INTERACTION:
Drugs Metabolized by CYP450:
Rabeprazole is metabolized by the cytochrome P450 (CYP450) drug metabolizing enzyme system. Studies in healthy subjects have shown that rabeprazole does not have clinically significant interactions with other drugs metabolized by the CYP450 system; such as warfarin and theophylline given as

single oral doses

; diazepam as a single

intravenous dose

and phenytoin given as a single intravenous dose (with supplemental oral dosing). Steady state

interactions of rabeprazole

and other drugs metabolized by this enzyme system have not been studied in patients

Warfarin:
There have been reports of increased INR and prothrombin time in patients receiving proton pump inhibitors, including rabeprazole and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death

Cyclosporine:
In vitro incubations employing human liver microsomes indicated that rabeprazole inhibited cyclosporine metabolism with an IC50 of 62 micromolar; a concentration that is over 50 times higher than the Cmax in healthy volunteers following 14 days of dosing with

20 mg of rabeprazole

. This degree of inhibition is similar to that by omeprazole at equivalent concentrations

Compounds Dependent on Gastric pH for Absorption:
Due to its effects on gastric acid secretion; rabeprazole can reduce the absorption of drugs where gastric pH is an important determinant of their bioavailability. Like with other drugs that decrease the intragastric acidity; the absorption of drugs such as ketoconazole; atazanavir; iron salts; erlotinib; and mycophenolate mofetil (MMF) can decrease, while the absorption of drugs such as digoxin can increase during

treatment with rabeprazole

Concomitant

treatment with rabeprazole

(20 mg daily) and ketoconazole in healthy subjects decreased the bioavailability of ketoconazole by 30% and increased the AUC and Cmax for digoxin by 19% and 29% respectively. Therefore; patients may need to be monitored when such drugs are taken concomitantly with rabeprazole.

Co-administration of rabeprazole

and antacids produced no clinically relevant changes in plasma rabeprazole concentrations.
Concomitant use of atazanavir and PPIs is not recommended. Co- administration of atazanavir with PPIs is expected to substantially decrease atazanavir plasma concentrations and thereby reduce its therapeutic effect.
Co-administration of PPIs in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite; mycophenolic acid (MPA); possibly due to a decrease in MMF solubility at an increased gastric pH. The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving PPIs and MMF. Use rabeprazole with caution in transplant patients receiving MMF

Drugs Metabolized by CYP2C19:
In a clinical study in Japan evaluating rabeprazole in adult patients categorized by CYP2C19 genotype (n=6 per genotype category); gastric acid suppression was higher in poor metabolizers as compared to extensive metabolizers. This could be due to higher rabeprazole plasma levels in poor metabolizers. Whether or not interactions of rabeprazole sodium with other drugs metabolized by CYP2C19 would be different between extensive metabolizers and poor metabolizers has not been studied

Combined Administration with Clarithromycin:
Combined administration consisting of rabeprazole; amoxicillin; and clarithromycin resulted in increases in

plasma concentrations of rabeprazole

and 14-hydroxyclarithromycin Concomitant administration of clarithromycin with other drugs can lead to serious adverse reactions due to drug interactions Because of these drug interactions; clarithromycin is contraindicated for co-administration with certain drugs

Methotrexate:
Case reports; published population pharmacokinetic studies; and retrospective analyses suggest that concomitant administration of PPIs and methotrexate (primarily at

high dose

; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate. However, no formal drug interaction studies of methotrexate with PPIs have been conducted

Clopidogrel:
Concomitant

administration of rabeprazole

and clopidogrel in healthy subjects had no clinically meaningful effect on exposure to the active metabolite of clopidogrel. No dose adjustment of clopidogrel is necessary when administered with an approved

dose of rabeprazole

PHARMACOKINETICS:
Absorption:
Time for Maximum Plasma Concentration (Tmax):
Oral; delayed-release

tablet

: 2 to 5 hours
10mg granules empty stomach: 2.5 hours

Bioavailability:
Oral; delayed-release tablet: approximately 52%
Effect of food (delayed-release tablet):
Maximum Plasma concentration (Cmax) and AUC not significantly altered; Tmax may be delayed up to 4 hours with high-fat meal; may be taken with or without meals

Effect of food (delayed-release granules):
Decreased Maximum serum concentration (Cmax) and AUC; Tmax delayed; should be taken 30 minutes before a meal

Distribution:
Plasma Protein Binding: 96.3%

Metabolism:
Hepatic: extensive via CYP3A; CYP2C19; and systemic nonenzymatic reduction
Metabolites: desmethyl rabeprazole; thioether; and sulphone
Substrate of CYP2C19

Excretion:
Fecal: approximately 10% primarily as metabolites
Renal: approximately 90% primarily as metabolites
Dialyzable: No
Total body clearance (adult): 4 to 8 mL/min/kg
Total body clearance (1 to 11 years): 8 to 13.5 L/hr

Elimination:
1 to 2 hours
Cirrhosis (mild to moderate): 2- to 3-fold longer

PRECAUTION:
Beers Criteria:
Avoid scheduled

use in older adults

for longer than 8 weeks due to risk of Clostridium difficile infection and bone loss and fractures; unless needed for high-risk patients (e.g.; oral corticosteroids; chronic NSAID use) erosive esophagitis; pathological hypersecretory condition; or need for maintenance treatment (e.g.; due to failure of drug discontinuation or histamine-2 blockers).

Concomitant use:
Use with nelfinavir should be avoided.

Dermatologic:
New or worsening cutaneous lupus erythematosus has been reported within weeks to years after continuous drug therapy; avoid using for longer than medically indicated and discontinue use if suspected.

Endocrine and metabolic:
Vitamin B12 deficiency may occur with

prolonged use

(eg greater than 1 to 2 years); monitoring recommended.

Endocrine and metabolic:
Hypomagnesemia has been reported in patients treated with proton pump inhibitors for at least 3 months; tetany; arrhythmias; and seizures may occur; monitoring recommended with

prolonged use

or concomitant drugs that may cause hypomagnesemia; discontinuation may be required.

Gastrointestinal:
Symptomatic response does not preclude the presence of gastric malignancy in adults
Clostridium difficile-associated diarrhea may occur; especially in hospitalized patients;

use lowest dose

and shortest duration.

Immunologic:
New or worsening systemic lupus erythematosus has been reported within days to years of treatment initiation; avoid using for longer than medically indicated and discontinue use if suspected.

Musculoskeletal:
Osteoporosis-related bone fracture of hip; wrist; or spine may occur; especially with higher (multiple daily) doses or longer duration of therapy (1 year or longer);

use lowest dose

and shortest treatment duration

Renal:
Acute interstitial nephritis; generally considered an idiopathic hypersensitivity reaction; has been reported; discontinuation required.

PREGNANCY CATEGORY:
Fetal Risk cannot br ruled out

BREAST FEEDING:
Infant Risk cannot be Ruled out

MONITORING:
GERD:
Decreased abdominal and gastroesophageal discomfort may indicate efficacy.

Peptic ulcer:
Endoscopic improvement may indicate efficacy.

Serum magnesium:
Routine screening is not necessary; consider screening prior to initiation and periodically during prolonged therapy.

Serum vitamin B12:
Although no routine screening is needed; may consider screening every 1 to 2 years for deficiency in patients receiving prolonged therapy.

HOW TO TAKE OR ADMINISTRATION:
Oral:
(Delayed-release tablet) may be taken with or without food; swallow whole; do not chew, crush, or split
For duodenal ulcers, tablet should be taken after the morning meal; for Helicobacter pylori eradication, the 3-drug combination should be taken together with the morning and evening meals

(Delayed-release capsule)
In children 1 to 11 years of age, administer 30 minutes prior to meal
Open capsule and sprinkle entire contents on small amount of soft food or liquid that is at or below room temperature; take within 15 minutes
Do not chew or crush granules
Do not store prepared mixture for future use

DOSAGE FORM:
Oral Tablet (Enteric Coated):
20 mg

Oral Capsule, Delayed Release:
5 mg
10 mg

TREATMENTS:
MANAGEMENT OF MILD TO MODERATE TOXICITY:
Treatment is symptomatic and supportive. Correct any significant fluid and/or electrolyte abnormalities in patients with severe diarrhea and/or vomiting.

MANAGEMENT OF SEVERE TOXICITY:
Treatment is symptomatic and supportive. Significant toxicity is not expected after an

overdose

.

TOXICOLOGY:
Doses up to 2400mg (120 times the usual Recommended

clinical dose

)resulted in transient effects (e.g.; drowsiness;confusion and tachycardia);with no serious events reported when taken alone.

PATIENT COUNSELING OR CLINICAL TEACHING:
Warn patient to report diarrhea that does not improve and consult healthcare professional prior to taking antidiarrheal medicine
Counsel patient to report symptoms of cutaneous or systemic lupus erythematosus
Advise patient using multiple

daily doses

for longer than a year to report symptoms of osteoporosis-related fractures (e.g.; hip; wrist; spine)
Side effects may include abdominal pain; diarrhea; nausea; vomiting; flatulence; constipation; pharyngitis; and headaches
Counsel patient to report symptoms of hypomagnesemia
Delayed-release capsules: Advise patient not to swallow capsule whole. Contents of capsule must be sprinkled on small amount of soft food or in liquid and consumed within 15 minutes after mixing and 30 minutes before a meal
Delayed-release tablets: Instruct patient with a duodenal ulcer to take drug after a meal. A patient with Helicobacter pylori infection should take drug with food

Click Here For Download PDF File of Rabeprazole sodium


Disclaimer:
For the Registered Medical Practitioner Only. We are not recommended for self medication. self medication is may harmful for health. We are only Provide information about medicine.