Omnitrope 6.7 mg / ml solution for Injection

1. Name Of The Medicinal Product

Omnitrope 6.7 mg/ml solution for injection

2. Qualitative And Quantitative Composition

Somatropin* 6.7 mg (corresponding to 20 IU)/ ml.

One cartridge contains 1.5 ml corresponding to 10 mg Somatropin* (30 IU).

* produced in Escherichia coli by recombinant DNA technology.

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Solution for injection

The solution is clear and colourless.

4. Clinical Particulars

4.1 Therapeutic Indications

Infants, children and adolescents

- Growth disturbance due to insufficient secretion of growth hormone (GH).

- Growth disturbance associated with Turner syndrome.

- Growth disturbance associated with chronic renal insufficiency.

- Growth disturbance (current height standard deviation score (SDS) < -2.5 and parental adjusted SDS < -1) in short children/adolescents born small for gestational age (SGA), with a birth weight and/or length below -2 standard deviation (SD), who failed to show catch-up growth (height velocity (HV) SDS < 0 during the last year) by 4 years of age or later.

- Prader-Willi syndrome (PWS), for improvement of growth and body composition. The diagnosis of PWS should be confirmed by appropriate genetic testing.

Adults

- Replacement therapy in adults with pronounced growth hormone deficiency. Patients with severe growth hormone deficiency in adulthood are defined as patients with known hypothalamic pituitary pathology and at least one known deficiency of a pituitary hormone not being prolactin. These patients should undergo a single dynamic test in order to diagnose or exclude a growth hormone deficiency. In patients with childhood onset isolated GH deficiency (no evidence of hypothalamic-pituitary disease or cranial irradiation), two dynamic tests should be recommended, except for those having low IGF-I concentrations (SDS < -2) who may be considered for one test. The cut-off point of the dynamic test should be strict.

4.2 Posology And Method Of Administration

Diagnosis and therapy with somatropin should be initiated and monitored by physicians who are appropriately qualified and experienced in the diagnosis and management of patients with growth disorders.

The posology and administration schedule should be individualised.

Growth disturbance due to insufficient secretion of growth hormone in paediatric patients:

Generally a dose of 0.025 - 0.035 mg/kg body weight per day or 0.7 - 1.0 mg/m² body surface area per day is recommended. Even higher doses have been used.

Prader-Willi syndrome, for improvement of growth and body composition in paediatric patients:

Generally a dose of 0.035 mg/kg body weight per day or 1.0 mg/m² body surface area per day is recommended. Daily doses of 2.7 mg should not be exceeded. Treatment should not be used in paediatric patients with a growth velocity less than 1 cm per year and near closure of epiphyses.

Growth disturbance due to Turner syndrome:

A dose of 0.045 - 0.050 mg/kg body weight per day or 1.4 mg/m² body surface area per day is recommended.

Growth disturbance in chronic renal insufficiency:

A dose of 1.4 mg/m² body surface area per day (0.045 - 0.050 mg/kg body weight per day) is recommended. Higher doses may be needed if growth velocity is too low. A dose correction may be needed after six months of treatment (see section 4.4).

Growth disturbance in short children/adolescents born small for gestational age (SGA):

A dose of 0.035 mg/kg body weight per day (1 mg/m² body surface area per day) is usually recommended until final height is reached (see section 5.1). Treatment should be discontinued after the first year of treatment if the height velocity SDS is below + 1. Treatment should be discontinued if height velocity is < 2 cm/year and, if confirmation is required, bone age is> 14 years (girls) or> 16 years (boys), corresponding to epiphyseal closure.

Dose recommendations for paediatric patients

Indication	mg/kg body weight dose per day	mg/m² body surface area dose per day
Growth hormone deficiency	0.025 - 0.035	0.7 - 1.0
Prader-Willi syndrome	0.035	1.0
Turner syndrome	0.045 - 0.050	1.4
Chronic renal insufficiency	0.045 - 0.050	1.4
Children/adolescents born small for gestational age (SGA)	0.035	1.0

Growth hormone deficient adult patients:

Therapy should start with a low dose, 0.15 - 0.3 mg per day. The dose should be gradually increased according to individual patient requirements as determined by the IGF-I concentration. Treatment goal should be insulin-like growth factor (IGF-I) concentrations within 2 SDS from the age corrected mean of healthy adults. Patients with normal IGF-I concentrations at the start of the treatment should be administered growth hormone up to an IGF-I level into the upper range of normal, not exceeding the 2 SDS. Clinical response and undesirable effects may also be used as guidance for dose titration. The daily maintenance dose rarely exceeds 1.0 mg per day. Women may require higher doses than men, while men show an increasing IGF-I sensitivity over time. This means that there is a risk that women, especially those on oral oestrogen replacement are under-treated while men are over-treated. The accuracy of the growth hormone dose should therefore be controlled every 6 months. As normal physiological growth hormone production decreases with age, dose requirements may be reduced. The minimum effective dose should be used.

The injection should be given subcutaneously and the site varied to prevent lipoatrophy.

For instructions for use and handling see section 6.6.

4.3 Contraindications

- Hypersensitivity to somatropin or to any of the excipients.

- Somatropin must not be used when there is any evidence of tumour activity and anti-tumour therapy must be completed prior to starting therapy.

- Somatropin must not be used for growth promotion in patients with closed epiphyses.

- Patients with acute critical illness suffering complications following open heart surgery, abdominal surgery, multiple accidental trauma, acute respiratory failure or similar conditions must not be treated with somatropin. With regard to patients undergoing substitution therapy, see section 4.4.

4.4 Special Warnings And Precautions For Use

Somatropin may induce a state of insulin resistance and in some patients hyperglycaemia. Therefore patients should be observed for evidence of glucose intolerance. In rare cases the diagnostic criteria for diabetes mellitus type II may be fulfilled as a result of the somatropin therapy, but risk factors such as obesity (including obese PWS patients), family history, steroid treatment, or pre-existing impaired glucose tolerance have been present in most cases where this occurred. In patients with already manifested diabetes mellitus, the anti-diabetic therapy might require adjustment when somatropin is instituted.

During treatment with somatropin, an enhanced T4 to T3 conversion has been found which may result in a reduction in serum T4 and an increase in serum T3 concentrations. In general, the peripheral thyroid hormone levels have remained within the reference ranges for healthy subjects. The effects of somatropin on thyroid hormone levels may be of clinical relevance in patients with central subclinical hypothyroidism in whom hypothyroidism theoretically may develop. Conversely, in patients receiving replacement therapy with thyroxin mild hyperthyroidism may occur. It is therefore particularly advisable to test thyroid function after starting treatment with somatropin and after dose adjustments.

Somatropin has been reported to reduce serum cortisol levels, possibly by affecting carrier proteins or by increasing hepatic clearance. The clinical relevance of these findings may be limited. Nevertheless, corticosteroid replacement therapy should be optimised before initiation of Omnitrope therapy.

In growth hormone deficiency, secondary to treatment of malignant disease, it is recommended to pay attention to signs of relapse of the malignancy.

In patients with endocrine disorders, including growth hormone deficiency, slipped epiphyses of the hip may occur more frequently than in the general population. Patients limping during treatment with somatropin, should be examined clinically.

In case of severe or recurrent headache, visual problems, nausea and/or vomiting, a fundoscopy for papilloedema is recommended. If papilloedema is confirmed, a diagnosis of benign intracranial hypertension should be considered and, if appropriate, the growth hormone treatment should be discontinued. At present there is insufficient evidence to give specific advice on the continuation of growth hormone treatment in patients with resolved intracranial hypertension. However, clinical experience has shown that reinstitution of the therapy is often possible without recurrence of the intracranial hypertension. If growth hormone treatment is restarted, careful monitoring for symptoms of intracranial hypertension is necessary.

Experience in patients above 60 years is limited.

In patients with PWS, treatment should always be in combination with a calorie-restricted diet.

There have been reports of fatalities associated with the use of growth hormone in paediatric patients with PWS who had one or more of the following risk factors: severe obesity, history of respiratory impairment, sleep apnoea or unidentified respiratory infection. Patients with PWS and one or more of these risk factors may be at greater risk.

Patients with PWS should be evaluated for upper airway obstruction, sleep apnoea or respiratory infections before initiation of treatment with somatropin.

In case of signs of upper airway obstruction, the problem should be solved by a specialist before starting treatment with somatropin.

Sleep apnoea should be assessed before onset of growth hormone treatment by recognised methods such as polysomnography or overnight oxymetry, and monitored if sleep apnoea is suspected.

If during treatment with somatropin patients show signs of upper airway obstruction (including onset of or increased snoring), treatment should be interrupted, and a new ENT assessment performed.

All patients with PWS should be evaluated for sleep apnoea and monitored if sleep apnoea is suspected.

All patients with PWS should be monitored for signs of respiratory infections which should be diagnosed as early as possible and treated aggressively.

All patients with PWS should have effective weight control before and during treatment with somatropin.

Scoliosis is common in patients with PWS. Scoliosis may progress in any child during rapid growth. Signs of scoliosis should be monitored during treatment. However, growth hormone treatment has not been shown to increase the incidence or severity of scoliosis.

Experience with long term treatment in adults and in patients with PWS is limited.

In short children/adolescents born SGA, other medical reasons or treatments that could explain growth disturbance should be ruled out before starting treatment.

In SGA children/adolescents it is recommended to measure fasting insulin and blood glucose before start of treatment and annually thereafter. In patients with increased risk for diabetes mellitus (e.g. familial history of diabetes, obesity, severe insulin resistance, acanthosis nigricans) oral glucose tolerance testing (OGTT) should be performed. If overt diabetes occurs, growth hormone should not be administered.

In SGA children/adolescents it is recommended to measure the IGF-I level before start of treatment and twice a year thereafter. If on repeated measurements IGF-I levels exceed +2 SD compared to references for age and pubertal status, the IGF-I / IGFBP-3 ratio could be taken into account to consider dose adjustment.

Experience in initiating treatment in SGA patients near onset of puberty is limited. It is therefore not recommended to initiate treatment near onset of puberty. Experience in patients with Silver-Russell syndrome is limited.

Some of the height gain obtained with treating short children/adolescents born SGA with growth hormone may be lost if treatment is stopped before final height is reached.

In chronic renal insufficiency, renal function should be below 50 percent of normal before institution of therapy. To verify growth disturbance, growth should be followed for a year preceding institution of therapy. During this period, conservative treatment for renal insufficiency (which includes control of acidosis, hyperparathyroidism and nutritional status) should have been established and should be maintained during treatment.

The treatment should be discontinued at renal transplantation.

To date, no data on final height in patients with chronic renal insufficiency treated with Omnitrope are available.

The effects of somatropin on recovery were studied in two placebo controlled trials involving 522 critically ill adult patients suffering complications following open heart surgery, abdominal surgery, multiple accidental trauma or acute respiratory failure. Mortality was higher in patients treated with 5.3 or 8 mg somatropin daily compared to patients receiving placebo, 42% vs. 19%. Based on this information, these types of patients should not be treated with somatropin. As there is no information available on the safety of growth hormone substitution therapy in acutely critically ill patients, the benefits of continued treatment in this situation should be weighed against the potential risks involved.

In all patients developing other or similar acute critical illness, the possible benefit of treatment with somatropin must be weighed against the potential risk involved.

This medicinal product contains less than 1 mmol sodium (23 mg) per ml, i.e. essentially 'sodium- free'.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Data from an interaction study performed in growth hormone deficient adults suggests that somatropin administration may increase the clearance of compounds known to be metabolised by cytochrome P450 isoenzymes. The clearance of compounds metabolised by cytochrome P 450 3A4 (e.g. sex steroids, corticosteroids, anticonvulsants and ciclosporin) may be especially increased resulting in lower plasma levels of these compounds. The clinical significance of this is unknown.

Also see section 4.4 for statements regarding diabetes mellitus and thyroid disorder and section 4.2 for statement on oral oestrogen replacement therapy.

4.6 Pregnancy And Lactation

For Omnitrope no clinical data on exposed pregnancies are available. Animal experimental data on reproductive toxicity of Omnitrope are not available. Treatment with Omnitrope should be interrupted if pregnancy occurs.

During normal pregnancy levels of pituitary growth hormone fall markedly after 20 gestation weeks, being replaced almost entirely by placental growth hormone by 30 weeks. In view of this, it is unlikely that continued replacement therapy with somatropin would be necessary in growth hormone deficient women in the third trimester of pregnancy.

It is not known if somatropin is excreted into breast milk, but absorption of intact protein from the gastrointestinal tract of the infant is extremely unlikely.

Caution should be exercised when Omnitrope is administered to breast-feeding women.

4.7 Effects On Ability To Drive And Use Machines

No studies on the effects on the ability to drive and use machines have been performed.

4.8 Undesirable Effects

Within the organ system classes, adverse reactions are listed under headings of frequency (number of patients expected to experience the reaction), using the following categories: very common (

Patients with growth hormone deficiency are characterised by extracellular volume deficit. When treatment with somatropin is started this deficit is rapidly corrected. In adult patients, adverse reactions related to fluid retention, such as peripheral oedema, stiffness in the extremities, arthralgia, myalgia and paraesthesia are common. In general these adverse reactions are mild to moderate, arise within the first months of treatment and subside spontaneously or with dose-reduction. The incidence of these undesirable effects is related to the administered dose, the age of patients, and possibly inversely related to the age of patients at the onset of growth hormone deficiency. In paediatric patients such undesirable effects are uncommon.

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Very rare:

Leukemia. Very rare cases of leukaemia have been reported in growth hormone deficient paediatric patients treated with somatropin, but the incidence appears to be similar to that in the paediatric subjects without growth hormone deficiency.

Immune system disorders

Common:

Formation of antibodies. Somatropin has given rise to the formation of antibodies in approximately 1% of the patients. The binding capacity of these antibodies has been low and no clinical changes have been associated with their formation.

Endocrine disorders

Rare:

Diabetes mellitus type II

Nervous system disorders

Common:	In adults: paraesthesia
Uncommon:	In adults: carpal tunnel syndrome; In paediatric patients: paraesthesia
Rare:	Benign intracranial hypertension

Musculoskeletal and connective tissue disorders

Common:	In adults: stiffness in the extremities, arthralgia, myalgia
Uncommon:	In paediatric patients: stiffness in the extremities, arthralgia, myalgia

General disorders and administration site conditions

Common:	In adults: peripheral oedema; In paediatric patients: transient local skin reactions at the injection site
Uncommon:	In paediatric patients: peripheral oedema

4.9 Overdose

No case of overdose has been reported.

Acute overdose could lead initially to hypoglycaemia and subsequently to hyperglycaemia.

Long-term overdose could result in signs and symptoms consistent with the known effects of human growth hormone excess.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: anterior pituitary lobe hormones and analogues.

ATC code: H01AC01.

Somatropin is a potent metabolic hormone of importance for the metabolism of lipids, carbohydrates and proteins. In children with inadequate endogenous growth hormone, somatropin stimulates linear growth and increases growth rate. In adults as well as in children, somatropin maintains a normal body composition by increasing nitrogen retention and stimulation of skeletal muscle growth, and by mobilisation of body fat. Visceral adipose tissue is particularly responsive to somatropin. In addition to enhanced lipolysis, somatropin decreases the uptake of triglycerides into body fat stores. Serum concentrations of IGF-I (Insulin-like Growth Factor-I) and IGFBP3 (Insulin-like Growth Factor Binding Protein 3) are increased by somatropin. In addition, the following actions have been demonstrated.

Lipid metabolism:

Somatropin induces hepatic LDL cholesterol receptors, and affects the profile of serum lipids and lipoproteins. In general, administration of somatropin to growth hormone deficient patients results in reduction in serum LDL and apolipoprotein B. A reduction in serum total cholesterol may also be observed.

Carbohydrate metabolism:

Somatropin increases insulin but fasting blood glucose is commonly unchanged. Children with hypopituitarism may experience fasting hypoglycaemia. This condition is reversed by somatropin.

Water and mineral metabolism:

Growth hormone deficiency is associated with decreased plasma and extracellular volumes. Both are rapidly increased after treatment with somatropin. Somatropin induces the retention of sodium, potassium and phosphorus.

Bone metabolism:

Somatropin stimulates the turnover of skeletal bone. Long-term administration of somatropin to growth hormone deficient patients with osteopoenia results in an increase in bone mineral content and density at weight-bearing sites.

Physical capacity:

Muscle strength and physical exercise capacity are improved after long-term treatment with somatropin. Somatropin also increases cardiac output, but the mechanism has yet to be clarified. A decrease in peripheral vascular resistance may contribute to this effect.

In clinical trials in short children/adolescents born SGA doses of 0.033 and 0.067 mg somatropin/kg body weight per day have been used for treatment until final height is reached. In 56 patients who are continuously treated and have reached (near) final height, the mean change from height at start of treatment was +1.90 SDS (0.033 mg/kg body weight per day) and +2.19 SDS (0.067 mg/kg body weight per day). Literature data from untreated SGA children/adolescents without early spontaneous catch-up suggest a late growth of 0.5 SDS. Long-term safety data are still limited.

5.2 Pharmacokinetic Properties

Absorption

The bioavailability of subcutaneously administered somatropin is approximately 80% in both healthy subjects and growth hormone deficient patients. A subcutaneous dose of 5 mg of Omnitrope 6.7 mg/ml solution for injection in healthy adults results in plasma Cmax and tmax values of 74 ± 22 µg/l and 3.9 ± 1.2 hours, respectively.

Elimination

The mean terminal half-life of somatropin after intravenous administration in growth hormone deficient adults is about 0.4 hours. However, after subcutaneous administration of Omnitrope 6.7 mg/ml solution for injection, a half-life of 3 hours is achieved. The observed difference is likely due to slow absorption from the injection site following subcutaneous administration.

Sub-populations

The absolute bioavailability of somatropin seems to be similar in males and females following subcutaneous administration.

Information about the pharmacokinetics of somatropin in geriatric and paediatric populations, in different races and in patients with renal, hepatic or cardiac insufficiency is either lacking or incomplete.

5.3 Preclinical Safety Data

In studies with Omnitrope regarding subacute toxicity and local tolerance, no clinically relevant effects have been observed.

In other studies with somatropin regarding general toxicity, local tolerance and reproduction toxicity no clinically relevant effects have been observed.

With somatropins, in vitro and in vivo genotoxicity studies on gene mutations and induction of chromosome aberrations have been negative.

An increased chromosome fragility has been observed in one in vitro study on lymphocytes taken from patients after long term treatment with somatropin and following the addition of the radiomimetic medicinal product bleomycin. The clinical significance of this finding is unclear.

In another study with somatropin, no increase in chromosomal abnormalities was found in the lymphocytes of patients who had received long-term somatropin therapy.

6. Pharmaceutical Particulars

6.1 List Of Excipients

disodium hydrogen phosphate heptahydrate

sodium dihydrogen phosphate dihydrate

glycine

poloxamer 188

phenol

water for injections

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3 Shelf Life

18 months.

Shelf life after first use:

After first use the cartridge should remain in the pen and has to be kept in a refrigerator (2°C - 8°C) for a maximum of 28 days. Store and transport refrigerated (2°C - 8°C). Do not freeze. Store in the original pen in order to protect from light.

6.4 Special Precautions For Storage

Unopened cartridge: Store and transport refrigerated (2°C - 8°C). Do not freeze. Store in the original package in order to protect from light.

For storage conditions of the in-use medicinal product, see section 6.3.

6.5 Nature And Contents Of Container

1.5 ml of solution in a cartridge (colourless type I glass) with plunger on one side (siliconised bromobutyl), a disc (bromobutyl) and a cap (aluminium) on the other side.

Pack sizes of 1, 5 and 10.

Not all pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

Omnitrope 6.7 mg/ml solution for injection is a sterile, ready-to-use solution for subcutaneous injection filled in a glass cartridge.

This presentation is intended for multiple use. It should only be administered with the Omnitrope Pen 10, an injection device specifically developed for use with Omnitrope 6.7 mg/ml solution for injection. It has to be administered using sterile, disposable pen needles. Patients and caregivers have to receive appropriate training and instruction on the proper use of the Omnitrope cartridges and the pen from the physician or other suitable qualified health professionals.

The following is a general description of the administration process. The manufacturer's instructions with each pen must be followed for loading the cartridge, attaching the injection needle and for the administration.

1. Hands should be washed.

2. If the solution is cloudy or contains particulate matter, it should not be used. The content must be clear and colourless.

3. Disinfect the rubber membrane of the cartridge with a cleansing swab

4. Insert the cartridge into the Omnitrope Pen 10 following the instructions for use provided with the pen.

5. Clean the site of injection with an alcohol swab.

6. Administer the appropriate dose by subcutaneous injection using a sterile pen needle. Remove the pen needle and dispose of it in accordance with local requirements.

7. Marketing Authorisation Holder

Sandoz GmbH

Biochemiestrasse 10

A-6250 Kundl

Austria

8. Marketing Authorisation Number(S)

EU/1/06/332/007

EU/1/06/332/008

EU/1/06/332/009

9. Date Of First Authorisation/Renewal Of The Authorisation

12 April 2006

10. Date Of Revision Of The Text

18 March 2008

Elixsure Decongestant

Generic Name: pseudoephedrine (SOO doe ee FED rin)

Brand Names: Chlor Trimeton Nasal Decongestant, Contac Cold, Drixoral Decongestant Non-Drowsy, Elixsure Decongestant, Entex, Genaphed, Kid Kare Drops, Nasofed, Seudotabs, Silfedrine, Sudafed, Sudafed 12-Hour, Sudafed 24-Hour, Sudafed Children's Nasal Decongestant, Sudodrin, SudoGest, SudoGest 12 Hour, Suphedrin, Triaminic Softchews Allergy Congestion, Unifed

What is Elixsure Decongestant (pseudoephedrine)?

Pseudoephedrine is a decongestant that shrinks blood vessels in the nasal passages. Dilated blood vessels can cause nasal congestion (stuffy nose).

Pseudoephedrine is used to treat nasal and sinus congestion, or congestion of the tubes that drain fluid from your inner ears, called the eustachian (yoo-STAY-shun) tubes.

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

What is the most important information I should know about Elixsure Decongestant (pseudoephedrine)?

Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children. Ask a doctor or pharmacist before using any other cough or cold medicine. Pseudoephedrine or other decongestants are contained in many combination medicines. Taking certain products together can cause you to get too much of a certain drug. Check the label to see if a medicine contains pseudoephedrine or a decongestant. Do not use pseudoephedrine if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days. A dangerous drug interaction could occur, leading to serious side effects.

What should I discuss with my healthcare provider before taking Elixsure Decongestant (pseudoephedrine)?

Do not use pseudoephedrine if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days. A dangerous drug interaction could occur, leading to serious side effects. Do not use this medication if you are allergic to pseudoephedrine or to other decongestants, diet pills, stimulants, or ADHD medications.

Ask a doctor or pharmacist if it is safe for you to take pseudoephedrine if you have:

• 
  

  heart disease or high blood pressure;

  
  


• 
  

  diabetes; or

  
  


• 
  

  a thyroid disorder.

  
  

FDA pregnancy category C. It is not known whether pseudoephedrine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication. Pseudoephedrine can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Artificially sweetened liquid cold medicine may contain phenylalanine. If you have phenylketonuria (PKU), check the medication label to see if the product contains phenylalanine.

How should I take Elixsure Decongestant (pseudoephedrine)?

Use exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Cold medicine is usually taken only for a short time until your symptoms clear up.

Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children. Take this medicine with a full glass of water. Do not crush, chew, or break an extended-release tablet. Swallow it whole. Breaking or opening the pill may cause too much of the drug to be released at one time. You may need to shake the oral suspension (liquid) well just before you measure a dose. Measure the liquid with a special dose measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose measuring device, ask your pharmacist for one. Do not take pseudoephedrine for longer than 7 days in a row. Talk with your doctor if your symptoms do not improve after 7 days of treatment, or if you have a fever with a headache, cough, or skin rash. If you need surgery, tell the surgeon ahead of time that you are using pseudoephedrine. You may need to stop using the medicine for a short time. Store at room temperature away from moisture and heat.

What happens if I miss a dose?

Since pseudoephedrine is taken as needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include feeling restless or nervous.

What should I avoid while taking Elixsure Decongestant (pseudoephedrine)?

Avoid taking this medication if you also take diet pills, caffeine pills, or other stimulants (such as ADHD medications). Taking a stimulant together with a decongestant can increase your risk of unpleasant side effects.

Ask a doctor or pharmacist before using any other cough or cold medicine. Pseudoephedrine or other decongestants are contained in many combination medicines. Taking certain products together can cause you to get too much of a certain drug. Check the label to see if a medicine contains pseudoephedrine or a decongestant.

Elixsure Decongestant (pseudoephedrine) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using pseudoephedrine and call your doctor at once if you have a serious side effect such as:

• 
  

  fast, pounding, or uneven heartbeat;

  
  


• 
  

  severe dizziness or anxiety;

  
  


• 
  

  easy bruising or bleeding, unusual weakness, fever, chills, body aches, flu symptoms; or

  
  


• 
  

  dangerously high blood pressure (severe headache, blurred vision, ringing in your ears, anxiety, confusion, chest pain, trouble breathing, uneven heart rate, seizure).

  
  

Less serious side effects may include:

• 
  

  loss of appetite;

  
  


• 
  

  warmth, tingling, or redness under your skin;

  
  


• 
  

  feeling restless or excited (especially in children);

  
  


• 
  

  sleep problems (insomnia); or

  
  


• 
  

  skin rash or itching.

  
  

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Elixsure Decongestant (pseudoephedrine)?

Tell your doctor about all other medicines you use, especially:

• 
  

  blood pressure medications;

  
  


• 
  

  a beta blocker such as atenolol (Tenormin, Tenoretic), carvedilol (Coreg), labetalol (Normodyne, Trandate), metoprolol (Dutoprol, Lopressor, Toprol), nadolol (Corgard), propranolol (Inderal, InnoPran), sotalol (Betapace), and others; or

  
  


• 
  

  an antidepressant such as amitriptyline (Elavil, Vanatrip, Limbitrol), doxepin (Sinequan), nortriptyline (Pamelor), and others.

  
  

This list is not complete and other drugs may interact with pseudoephedrine. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Elixsure Decongestant resources

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

• Pseudoephedrine MedFacts Consumer Leaflet (Wolters Kluwer)


• Pseudoephedrine Monograph (AHFS DI)


• Cenafed Advanced Consumer (Micromedex) - Includes Dosage Information


• Dimetapp Decongestant Drops MedFacts Consumer Leaflet (Wolters Kluwer)


• Drixoral Non-Drowsy Sustained-Release Capsules MedFacts Consumer Leaflet (Wolters Kluwer)


• Entex Liquid MedFacts Consumer Leaflet (Wolters Kluwer)


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• Sudafed Consumer Overview


• Tylenol Simply Stuffy Liquid MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Elixsure Decongestant with other medications

• Nasal Congestion

Where can I get more information?

• Your pharmacist can provide more information about pseudoephedrine.

See also: Elixsure Decongestant side effects (in more detail)

levonorgestrel

lee-voe-nor-JES-trel

Commonly used brand name(s)

In the U.S.

• Next Choice


• Plan B


• Plan B One-Step

Available Dosage Forms:

• Tablet

Therapeutic Class: Contraceptive, Progestin

Pharmacologic Class: Progestin

Uses For levonorgestrel

Levonorgestrel is an emergency contraceptive that is used to prevent pregnancy after unprotected sex or after failure of another birth control method. It works by preventing a woman's egg from fully developing. It may also prevent the attachment of the woman's egg to the wall of the uterus (womb).

No contraceptive method is 100 percent effective. Birth control methods such as having surgery to become sterile or not having sex are more effective. levonorgestrel should not be used as a regular method of birth control. Discuss with your doctor your options for birth control.

levonorgestrel is available only under a special distribution program called Convenient Access, Responsible Education (CARE) program.

Before Using levonorgestrel

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 levonorgestrel, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to levonorgestrel 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 levonorgestrel in teenage females. levonorgestrel may be used for birth control in teenage females but is not recommended before the start of menstruation.

Geriatric

Appropriate studies on the relationship of age to the effects of levonorgestrel have not been performed in the geriatric population. levonorgestrel is not indicated for use in elderly women.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	X	Studies in animals or pregnant women have demonstrated positive evidence of fetal abnormalities. This drug should not be used in women who are or may become pregnant because the risk clearly outweighs any possible benefit.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

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. When you are taking levonorgestrel, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using levonorgestrel with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Isotretinoin


• Theophylline


• Tizanidine


• Tranexamic Acid

Using levonorgestrel with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acitretin


• Alprazolam


• Amoxicillin


• Ampicillin


• Amprenavir


• Aprepitant


• Atazanavir


• Bacampicillin


• Betamethasone


• Bexarotene


• Bosentan


• Carbamazepine


• Colesevelam


• Cyclosporine


• Darunavir


• Delavirdine


• Doxycycline


• Efavirenz


• Etravirine


• Fosamprenavir


• Fosaprepitant


• Fosphenytoin


• Griseofulvin


• Lamotrigine


• Licorice


• Minocycline


• Modafinil


• Mycophenolate Mofetil


• Mycophenolic Acid


• Nelfinavir


• Nevirapine


• Oxcarbazepine


• Oxytetracycline


• Phenobarbital


• Phenytoin


• Pioglitazone


• Prednisolone


• Primidone


• Rifabutin


• Rifampin


• Rifapentine


• Ritonavir


• Rosuvastatin


• Rufinamide


• Selegiline


• St John's Wort


• Tacrine


• Telaprevir


• Tetracycline


• Topiramate


• Troglitazone


• Troleandomycin


• Voriconazole


• Warfarin

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. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using levonorgestrel with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use levonorgestrel, or give you special instructions about the use of food, alcohol, or tobacco.

• Caffeine

Proper Use of levonorgestrel

To make using emergency contraceptives as safe and reliable as possible, you should understand how and when to use them and what effects may be expected.

levonorgestrel comes with a patient information leaflet. Read and follow the instructions carefully. Ask your doctor if you have any questions.

Plan B® and Plan B® One-Step is available as an over-the-counter medicine for women 17 years of age and older, and is available only with a doctor's prescription for women younger than 17 years of age.

Use levonorgestrel exactly as directed by your doctor. levonorgestrel is for occasional use as an emergency birth control. It should not replace your regular birth control method. You may use levonorgestrel at any time during your monthly period.

If you vomit within 2 hours of taking levonorgestrel, call your doctor right away. Your doctor may prescribe another tablet for you.

Dosing

The dose of levonorgestrel 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 levonorgestrel. 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 emergency contraception:
  
  • For oral dosage form (Plan B® One-Step tablets):
    
    • Adults and teenagers 17 years of age and older—One tablet taken as soon as possible not more than 72 hours (3 days) after unprotected sex or after failure of another birth control method.
    
    
    • Children younger than 17 years of age—Use and dose must be determined by your doctor.
    
    
  
  
  • For oral dosage form (Plan B® tablets):
    
    • Adults and teenagers 17 years of age and older—One tablet taken as soon as possible not more than 72 hours (3 days) after unprotected sex or after failure of another birth control method. A second tablet should be taken 12 hours after the first dose.
    
    
    • Children younger than 17 years of age—Use and dose must be determined by your doctor.
    
    
  
  

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 levonorgestrel

It is very important that your doctor check you closely to make sure levonorgestrel is working properly and does not cause unwanted effects.

Although you are using levonorgestrel to prevent pregnancy, you should know that using levonorgestrel while you are pregnant could harm the unborn baby. Your doctor may give you a pregnancy test before you start using levonorgestrel to make sure you are not pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away.

Call your doctor right away if you have severe lower abdominal or stomach pain 3 to 5 weeks after taking levonorgestrel. You may have a pregnancy outside of the uterus (womb), which is called an ectopic pregnancy. An ectopic pregnancy can be a serious and life-threatening condition. It can also cause problems that may make it harder for you to become pregnant in the future.

You may have some blood spotting a few days after taking levonorgestrel. If the bleeding continues for more than 1 week, check with your doctor right away.

levonorgestrel may make your next monthly period later than expected by a few days. If your next period after taking levonorgestrel is more than 1 week late, check with your doctor right away for a pregnancy test.

levonorgestrel will not protect you from getting HIV/AIDS or other sexually transmitted infections. If this is a concern for you, talk with your doctor.

Your regular birth control method such as birth control pills or patch may not work as well while you are using levonorgestrel. After using levonorgestrel, you must use two forms of birth control. Use birth control pills or patch together with another form of birth control, such as a condom, diaphragm, or contraceptive foam or jelly, during any other times that you have sex in the same monthly period you used levonorgestrel.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (e.g., St. John's wort) or vitamin supplements.

levonorgestrel 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

• Heavy or light menstrual bleeding

Incidence not known

• Absent missed or irregular menstrual periods


• cramps


• irregular menstruation


• pain


• pain in the pelvis


• stopping of menstrual bleeding

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:

More common

• Abdominal or stomach pain


• dizziness


• headache


• nausea


• tenderness of the breasts


• unusual tiredness or weakness


• vomiting

Less common

• Diarrhea

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: levonorgestrel 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 levonorgestrel resources

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

• Levonorgestrel MedFacts Consumer Leaflet (Wolters Kluwer)


• Levonorgestrel Professional Patient Advice (Wolters Kluwer)


• Mirena Prescribing Information (FDA)


• Mirena Consumer Overview


• Mirena IUD MedFacts Consumer Leaflet (Wolters Kluwer)


• Next Choice Prescribing Information (FDA)


• Plan B Prescribing Information (FDA)


• Plan B Consumer Overview


• Plan B One-Step Consumer Overview


• Plan B One-Step MedFacts Consumer Leaflet (Wolters Kluwer)

Compare levonorgestrel with other medications

• Abnormal Uterine Bleeding
• Birth Control
• Emergency Contraception

Livalo

Generic Name: Pitavastatin Calcium
Class: HMG-CoA Reductase Inhibitors
VA Class: CV350
Molecular Formula: C₅₀H₄₆CaF₂N₂O₈

Introduction

Antilipemic agent; hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor (i.e., statin).¹

Uses for Livalo

Dyslipidemias

Adjunct to dietary therapy to decrease elevated serum total cholesterol, LDL-cholesterol, apolipoprotein B (apo B), and triglyceride concentrations, and to increase HDL-cholesterol concentrations in the management of primary hypercholesterolemia or mixed dyslipidemia.¹

Reductions in LDL-cholesterol concentrations achieved with usual dosages (1–4 mg daily) of pitavastatin are similar to or greater than those achieved with low to medium dosages of certain other statins (i.e., atorvastatin, pravastatin, simvastatin).^{1 3 4 5 9}

Safety and efficacy not established in patients with Fredrickson Type I, III, or V dyslipidemia.¹ Effect on cardiovascular morbidity and mortality not established.¹

Livalo Dosage and Administration

General

• 
  

  Patients should be placed on a standard lipid-lowering diet before initiation of pitavastatin therapy and should remain on this diet during treatment with the drug.¹

  
  

Monitoring during Antilipemic Therapy

• 
  

  Monitor lipoprotein concentrations periodically to ensure that target LDL-cholesterol goals are achieved and maintained at <100 mg/dL (optional goal: <70 mg/dL) for patients with CHD or CHD risk equivalents; <130 mg/dL (optional goal: <100 mg/dL) for patients with ≥2 risk factors and 10-year risk of 10–20%; <130 mg/dL for patients with ≥2 risk factors and 10-year risk <10%; or <160 mg/dL for patients with 0–1 risk factor.³²

  
  

Administration

Oral Administration

Administer orally once daily at any time of day, without regard to food.¹

Dosage

Available as pitavastatin calcium; dosage expressed in terms of pitavastatin.¹

Adults

Dyslipidemias

Primary Hypercholesterolemia or Mixed Dyslipidemia

Oral

Initially, 2 mg once daily.¹ Determine serum lipoprotein concentrations 4 weeks after initiating or titrating therapy and adjust dosage accordingly.¹ Usual maintenance dosage is 1–4 mg once daily.¹

Prescribing Limits

Adults

Dyslipidemias

Primary Hypercholesterolemia or Mixed Dyslipidemia

Oral

Maximum 4 mg once daily.¹

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.¹ (See Contraindications under Cautions, and also see Absorption: Special Populations and Elimination: Special Populations under Pharmacokinetics.)

Renal Impairment

Patients with moderate renal impairment (GFR 30–59 mL/minute per 1.73 m²) or patients with end-stage renal disease (ESRD) undergoing hemodialysis: Initially, 1 mg once daily.¹ Maximum 2 mg once daily.¹

Patients with severe renal impairment (GFR <30 mL/minute per 1.73 m²) not undergoing hemodialysis: Not evaluated systematically in this population; use not recommended.¹

Geriatric Patients

No specific dosage recommendations at this time.¹ (See Geriatric Use under Cautions.)

Cautions for Livalo

Contraindications

• 
  

  Active liver disease, including unexplained, persistent elevations of serum aminotransferase concentrations.¹

  
  


• 
  

  Pregnancy or lactation.¹ (See Lactation and also see Fetal/Neonatal Morbidity and Mortality under Cautions.)

  
  


• 
  

  Concomitant use with cyclosporine.¹ (See Specific Drugs and Foods under Interactions.)

  
  


• 
  

  Known hypersensitivity to pitavastatin or any ingredient in the formulation.¹

  
  

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity

Rash, pruritus, and urticaria reported.¹

Fetal/Neonatal Morbidity and Mortality

Suppression of cholesterol biosynthesis could cause fetal harm.¹ Congenital anomalies following intrauterine exposure to statins reported rarely.¹

Advise women of childbearing potential to use effective contraceptive methods during pitavastatin therapy.¹ If the patient becomes pregnant while taking the drug, discontinue therapy and apprise patient of potential fetal hazard.¹

Hepatic Effects

Associated with increases in serum aminotransferase (i.e., AST, ALT) concentrations.¹ Increases usually transient and resolve or improve with continued therapy or after temporary interruption of therapy.¹ Increases in alkaline phosphatase and bilirubin concentrations also reported.¹

Perform liver function tests prior to initiation of therapy, at 12 weeks after initiation of therapy or any increase in dosage, and periodically (e.g., semiannually) thereafter.¹

Patients who develop increased aminotransferase concentrations should be monitored until abnormalities return to normal.¹ If increases in AST or ALT concentrations >3 times the ULN persist, reduce dosage or discontinue therapy.¹

Use with caution in patients who consume substantial amounts of alcohol.¹ Contraindicated in patients with active liver disease, including unexplained, persistent elevations in serum aminotransferase concentrations.¹

Musculoskeletal Effects

Myopathy and rhabdomyolysis with acute renal failure secondary to myoglobinuria reported.¹ May occur at any dosage, but risk increases with increasing dosage; in clinical studies, risk of severe myopathy increased with dosages >4 mg daily.¹

Use with caution in patients with predisposing factors for myopathy (e.g., advanced age [>65 years of age], renal impairment, inadequately treated hypothyroidism) and in patients receiving concomitant therapy with certain antilipemic agents (i.e., fibric acid derivatives, antilipemic dosages of niacin).¹

Discontinue if serum CK concentrations become markedly elevated or if myopathy is diagnosed or suspected.¹ Temporarily withhold therapy in patients experiencing an acute, serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis (e.g., sepsis; hypotension; dehydration; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; uncontrolled seizures). (See Advice to Patients.)¹

Specific Populations

Pregnancy

Category X.¹ (See Contraindications and also see Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Distributed into milk in rats.¹ Not known whether distributed into human milk; however, a small amount of another statin is distributed into human milk.¹ Use is contraindicated; discontinue nursing or pitavastatin.¹

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age.^{1 29}

Geriatric Use

No substantial differences in safety or efficacy relative to younger adults, but increased sensitivity cannot be ruled out.¹

Hepatic Impairment

Contraindicated in patients with active liver disease, including unexplained, persistent elevations in serum aminotransferase concentrations.¹ (See Absorption: Special Populations and also Elimination: Special Populations, under Pharmacokinetics.)

Renal Impairment

Dosage adjustments necessary in patients with moderate renal impairment (GFR 30–59 mL/minute per 1.73 m²) and in patients with ESRD undergoing hemodialysis.¹ (See Renal Impairment under Dosage and Administration.)

Do not use in patients with severe renal impairment (GFR <30 mL/minute per 1.73 m²) who are not undergoing hemodialysis (inadequate data/experience).¹

Common Adverse Effects

Myalgia, back pain, diarrhea, constipation, pain in extremity.¹

Interactions for Livalo

Minimally metabolized by CYP isoenzymes 2C9 and 2C8.^{1 7 8}

Substrate of organic anionic transport polypeptide (OATP) 1B1 (OATP2) (see Extent under Pharmacokinetics);^{7 8 30} pharmacokinetic interactions observed with drugs that inhibit OATP1B1.^{1 7 9 30}

Specific Drugs and Foods

Drug or Food	Interaction	Comments
Cyclosporine	Substantially increased peak plasma concentrations and AUC of pitavastatin1	Concomitant use contraindicated1
Digoxin	Slight decrease in peak plasma concentrations and increase in AUC of pitavastatin1 Slight decrease in peak plasma concentrations and AUC of digoxin1	Not considered clinically important29
Enalapril	Decreased peak plasma concentrations and increased AUC of pitavastatin1 Increased peak plasma concentrations and AUC of enalapril1	Not considered clinically important29
Erythromycin	Substantially increased peak plasma concentrations and AUC of pitavastatin1	Do not exceed pitavastatin dosage of 1 mg once daily 1
Ezetimibe	Negligible decreases in peak plasma concentrations and AUC of pitavastatin1 Increased peak plasma concentrations and AUC of ezetimibe1	Not considered clinically important29
Fibric acid derivatives (e.g., gemfibrozil)	Possible pharmacodynamic interaction (increased risk of adverse musculoskeletal effects [e.g., myopathy, rhabdomyolysis])1 Increased peak plasma concentrations and AUC of pitavastatin; increases more pronounced when used concomitantly with gemfibrozil than with fenofibrate1	Use concomitantly with caution1
Grapefruit juice	Decreased peak plasma concentrations and increased AUC of pitavastatin1	Not considered clinically important29
HIV protease inhibitors	Atazanavir: Increased peak plasma concentrations and AUC of pitavastatin and atazanavir1 31 Ritonavir-boosted protease inhibitors: Possible increased pitavastatin concentrations and rhabdomyolysis1 31	Atazanavir: Not considered clinically important;29 dosage adjustment not necessary31 Ritonavir-boosted protease inhibitors: Manufacturer recommends avoiding concomitant use with lopinavir/ritonavir;1 however, some clinicians recommend avoiding concomitant use with any ritonavir-boosted protease inhibitor31
Itraconazole	Decreased peak plasma concentrations and AUC of pitavastatin1	Not considered clinically important29
Niacin (at antilipemic dosages29 )	Possible increased risk of adverse musculoskeletal effects (e.g., myopathy, rhabdomyolysis)1	Consider reducing pitavastatin dosage1
Rifampin	Substantially increased peak plasma concentrations and AUC of pitavastatin1 Decreased peak plasma concentrations and AUC of rifampin1	Do not exceed pitavastatin dosage of 2 mg once daily1
Warfarin	Pharmacokinetic and pharmacodynamic (i.e., effects on PT and INR) interaction unlikely1 Increased peak plasma concentrations and AUC of R-warfarin and S-warfarin1	Monitor PT and INR when pitavastatin is initiated in patients receiving warfarin1

Livalo Pharmacokinetics

Absorption

Bioavailability

Absorbed from GI tract, principally from small intestine, with very small amounts absorbed from colon.¹

Absolute bioavailability of oral solution (not commercially available in the US) is 51%.¹

Peak plasma concentrations attained approximately 1 hour after administration of tablets²⁹ .¹

Peak plasma concentrations and AUC increase in an approximately dose-proportional manner for single pitavastatin dosages of 1–24 mg once daily.¹

Peak plasma concentrations and AUC reportedly not different following evening or morning administration; however, reductions in LDL-cholesterol concentrations achieved with 4-mg tablets slightly higher following evening administration compared with morning administration in healthy individuals.¹

Onset

Therapeutic response observed within one week; maximal response occurs within 2–4 weeks.²⁹

Food

High-fat meal (50% fat content) reduces peak plasma concentrations by 43% but does not substantially reduce extent of absorption (i.e., AUC).¹

Special Populations

Race: Peak plasma concentrations or AUC are 21 or 5% lower, respectively, in black individuals compared with white individuals; no substantial differences in peak plasma concentrations and AUC observed among Japanese and white individuals.¹

Gender: Peak plasma concentrations or AUC are 60 or 54% higher, respectively, in healthy women compared with healthy men; however, no difference in safety or efficacy observed in clinical trials.¹

Geriatric patients: Peak plasma concentrations or AUC are 10 or 30% higher, respectively, in geriatric individuals (≥65 years of age) compared with younger adults.¹ (See Geriatric Use under Cautions.)

Hepatic impairment: Patients with aminotransferase (i.e., AST, ALT) concentrations >1.5 times the ULN were excluded from phase 3 clinical studies.^{3 4 29} In patients with mild (Child-Pugh class A) hepatic impairment, peak plasma concentrations or AUC are 1.3- or 1.6-fold higher, respectively, compared with healthy individuals.¹ In patients with moderate (Child-Pugh class B) hepatic impairment, peak plasma concentrations or AUC are 2.7- or 3.8-fold higher, respectively, compared with healthy individuals.¹

Renal impairment: Peak plasma concentrations or AUC are 60 or 79% higher, respectively, in patients with moderate renal impairment (GFR 30–59 mL/min per 1.73 m²) compared with healthy individuals.¹ In patients with ESRD undergoing hemodialysis, peak plasma concentrations or AUC are 40 or 86% higher, respectively, compared with healthy individuals.¹ Effects of mild or severe renal impairment on pitavastatin exposure are unknown.¹

Distribution

Extent

Crosses placenta and is distributed into milk in rats.¹ (See Pregnancy and also Lactation under Cautions.)

Undergoes carrier-mediated uptake into hepatocytes, principally via OATP1B1 (OATP2) and, to a lesser extent, by OATP1B3 and OATP2B1;^{7 8 29 33} hepatic uptake is required for pharmacologic effects.⁷

Plasma Protein Binding

>99% (mainly albumin and alpha 1-acid glycoprotein).¹

Special Populations

Patients undergoing hemodialysis have a 33 or 36% increase in mean unbound fraction of pitavastatin compared with healthy individuals or patients with moderate renal impairment, respectively.¹

Elimination

Metabolism

Principally metabolized by uridine 5′-diphosphate (UDP) glucuronosyltransferase (i.e., UGT1A1, UGT1A3, UGT2B7) to an ester-type pitavastatin glucuronide conjugate, which is further metabolized to the inactive metabolite pitavastatin lactone.^{1 7 8}

Minimally metabolized by CYP2C9 and CYP2C8.^{1 7 8}

Elimination Route

Excreted in feces (79%) and in urine (15%) within 7 days following administration of oral solution (not commercially available in the US).^{1 29}

Unlikely to be removed by hemodialysis because of high (>99%) protein binding.¹

Half-life

Approximately 12 hours.¹

Special Populations

Mean elimination half-life is prolonged in patients with mild (10 hours) or moderate (15 hours) hepatic impairment compared with healthy individuals (8 hours).¹

Stability

Storage

Oral

Tablets

15–30°C. ¹ Protect from light.¹

Actions

• 
  

  Inhibits HMG-CoA reductase, causing reduction in hepatic cholesterol biosynthesis; this leads to compensatory increase in expression of LDL receptors on hepatic cell surfaces and, subsequently, increased hepatic clearance of LDL-cholesterol from blood.^{1 7 8} Reduces serum concentrations of total cholesterol, LDL-cholesterol, VLDL-cholesterol, apo B, and triglyceride, and increases serum HDL-cholesterol concentrations in patients with primary hypercholesterolemia or mixed dyslipidemia.^{1 3 4 5 6}

  
  


• 
  

  Statins may slow progression of and/or induce regression of atherosclerosis in coronary and/or carotid arteries,^{10 11 12 13 14 15 16 17 18 19 20 21 22 23 28} modulate BP in hypercholesterolemic patients with hypertension,^{24 25} and possess anti-inflammatory activity.^{26 27}

  
  

Advice to Patients

• 
  

  Risk of myopathy and/or rhabdomyolysis.¹ Importance of promptly informing clinicians of any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever.¹

  
  


• 
  

  Importance of monitoring liver function prior to initiation of therapy, at 12 weeks after initiation of therapy or any increase in dosage, and periodically (e.g., semiannually) thereafter.¹

  
  


• 
  

  Importance of adhering to nondrug therapies and measures, including dietary management, weight control, physical activity, and management of potentially contributory disease (e.g., diabetes mellitus).²

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹ Necessity for clinicians to advise women to avoid pregnancy (i.e., using effective contraceptive methods) during therapy and to advise pregnant women of risk to the fetus.¹

  
  


• 
  

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

  
  


• 
  

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

  
  

Preparations

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

Pitavastatin Calcium

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	1 mg (of pitavastatin)	Livalo	Kowa
		2 mg (of pitavastatin)	Livalo	Kowa
		4 mg (of pitavastatin)	Livalo	Kowa

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 July 11, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Kowa Pharmaceuticals America, Inc. Livalo (pitavastatin calcium) tablets prescribing information. Montgomery, AL; 2010 Jul.

2. National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: Adult Treatment Panel III Report. From NIH web site.

3. Budinski D, Arneson V, Hounslow N, Grasiansky N. Pitavastatin compared with atorvastatin in primary hypercholesterolemia or combined dyslipidemia. Clin Lipidol. 2009; 4:291-302.

4. Ose L, Budinski D, Hounslow N et al. Comparison of pitavastatin with simvastatin in primary hypercholesterolaemia or combined dyslipidaemia. Curr Med Res Opin. 2009; 25:2755-64. [PubMed 19785568]

5. Stender S, Hounslow N. Robust efficacy of pitavastatin and comparable safety to pravastatin. Atherosclerosis Suppl. 2009; 10:945, abstract P770. [PubMed 20624769]

6. Ose L, Budinski D, Hounslow N et al. Long-term treatment with pitavastatin is effective and well tolerated by patients with primary hypercholesterolemia or combined dyslipidemia. Atherosclerosis. 2010; 210:202-8. [PubMed 20080236]

7. Wensel TM, Waldrop BA, Wensel B. Pitavastatin: a new HMG-CoA reductase inhibitor. Ann Pharmacother. 2010; 44:507-14. [PubMed 20179258]

8. Saito Y. Critical appraisal of the role of pitavastatin in treating dyslipidemias and achieving lipid goals. Vasc Health Risk Manag. 2009; 5:921-36. [PubMed 19997573]

9. Food and Drug Administration. Center for Drug Evaluation and Research: Application number 22-363: Summary Review. From FDA website. 2009 Aug 3.

10. Merck & Co., Inc. Mevacor (lovastatin) tablets prescribing information. White House Station, NJ; 2005 Nov.

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