Nalbuphine

Dosage Form: injection, solution
Nalbuphine HYDROCHLORIDE Injection

Ampul

Fliptop Vial

Protect from light.

Rx Only

Nalbuphine Description

Nalbuphine hydrochloride is a synthetic opioid agonist-antagonist analgesic of the phenanthrene series. It is chemically related to both the widely used opioid antagonist, naloxone, and the potent opioid analgesic, oxymorphone. Chemically Nalbuphine hydrochloride is 17-(cyclobutylmethyl)-4,5α-epoxymorphinan-3,6α,14-triol hydrochloride. Nalbuphine hydrochloride molecular weight is 393.91 and is soluble in H2O (35.5 mg/mL at 25ºC) and ethanol (0.8%); insoluble in CHCl3 and ether. Nalbuphine hydrochloride has pKa values of 8.71 and 9.96. The molecular formula is C21H27NO4 • HCl. The structural formula is:

Nalbuphine Hydrochloride Injection is a sterile, nonpyrogenic solution of Nalbuphine hydrochloride in water for injection. This product may be administered by subcutaneous, intramuscular or intravenous injection.

Each milliliter (mL) contains Nalbuphine hydrochloride 10 mg or 20 mg; sodium citrate, dihydrate 0.47 mg and citric acid, anhydrous 0.63 mg added as buffers and may contain sodium hydroxide and/or hydrochloric acid for pH adjustment; pH 3.7 (3.0 to 4.5). Contains sodium chloride for tonicity adjustment.

Multiple-dose vials contain 1.8 mg/mL methylparaben and 0.2 mg/mL propylparaben added as preservatives. Single-dose products contain no bacteriostat or antimicrobial agent and unused portions must be discarded.

Nalbuphine - Clinical Pharmacology

Nalbuphine hydrochloride is a potent analgesic. Its analgesic potency is essentially equivalent to that of morphine on a milligram basis. Receptor studies show that Nalbuphine hydrochloride binds to mu, kappa, and delta receptors, but not to sigma receptors. Nalbuphine hydrochloride is primarily a kappa agonist/partial mu antagonist analgesic.

The onset of action of Nalbuphine hydrochloride occurs within 2 to 3 minutes after intravenous administration, and in less than 15 minutes following subcutaneous or intramuscular injection. The plasma half-life of Nalbuphine is 5 hours, and in clinical studies, the duration of analgesic activity has been reported to range from 3 to 6 hours.

The opioid antagonist activity of Nalbuphine is one-fourth as potent as nalorphine and 10 times that of pentazocine.

Nalbuphine hydrochloride may produce the same degree of respiratory depression as equianalgesic doses of morphine. However, Nalbuphine hydrochloride exhibits a ceiling effect such that increases in dose greater than 30 mg do not produce further respiratory depression in the absence of other CNS active medications affecting respiration.

Nalbuphine hydrochloride by itself has potent opioid antagonist activity at doses equal to or lower than its analgesic dose. When administered following or concurrent with mu agonist opioid analgesics (e.g., morphine, oxymorphone, fentanyl), Nalbuphine hydrochloride may partially reverse or block opioid-induced respiratory depression from the mu agonist analgesic. Nalbuphine hydrochloride may precipitate withdrawal in patients dependent on opioid drugs. Nalbuphine hydrochloride should be used with caution in patients who have been receiving mu opioid analgesics on a regular basis.

Indications and Usage for Nalbuphine

Nalbuphine hydrochloride is indicated for the relief of moderate to severe pain. Nalbuphine hydrochloride can also be used as a supplement to balanced anesthesia, for preoperative and postoperative analgesia, and for obstetrical analgesia during labor and delivery.

Contraindications

Nalbuphine hydrochloride injection should not be administered to patients who are hypersensitive to Nalbuphine hydrochloride, or to any of the other ingredients in Nalbuphine hydrochloride injection.

Warnings

Nalbuphine hydrochloride injection should be administered as a supplement to general anesthesia only by persons specifically trained in the use of intravenous anesthetics and management of respiratory effects of potent opioids.

Naloxone hydrochloride injection, resuscitative and intubation equipment and oxygen should be readily available.

Drug Abuse

Caution should be observed in prescribing Nalbuphine for emotionally unstable patients, or for individuals with a history of opioid abuse. Such patients should be closely supervised when long term therapy is contemplated (see DRUG ABUSE AND DEPENDENCE).

Use in Ambulatory Patients

Nalbuphine may impair the mental or physical abilities required for the performance of potentially dangerous tasks such as driving a car or operating machinery. Therefore, Nalbuphine hydrochloride injection should be administered with caution to ambulatory patients who should be warned to avoid such hazards.

Use in Emergency Procedures

Maintain patient under observation until recovered from Nalbuphine effects that would affect driving or other potentially dangerous tasks.

Use in Pregnancy (Other Than Labor)

Severe fetal bradycardia has been reported when Nalbuphine is administered during labor. Naloxone may reverse these effects. Although there are no reports of fetal bradycardia earlier in pregnancy, it is possible that this may occur. This drug should be used in pregnancy only if clearly needed, if the potential benefit outweighs the risk to the fetus, and if appropriate measures such as fetal monitoring are taken to detect and manage any potential adverse effect on the fetus.

Use During Labor and Delivery

The placental transfer of Nalbuphine is high, rapid, and variable with a maternal to fetal ratio ranging from 1:0.37 to 1:6. Fetal and neonatal adverse effects that have been reported following the administration of Nalbuphine to the mother during labor include fetal bradycardia, respiratory depression at birth, apnea, cyanosis, and hypotonia. Some of these events have been life-threatening. Maternal administration of naloxone during labor has normalized these effects in some cases. Severe and prolonged fetal bradycardia has been reported. Permanent neurological damage attributed to fetal bradycardia has occurred. A sinusoidal fetal heart rate pattern associated with the use of Nalbuphine has also been reported. Nalbuphine should be used during labor and delivery only if clearly indicated and only if the potential benefit outweighs the risk to the infant. Newborns should be monitored for respiratory depression, apnea, bradycardia and arrhythmias if Nalbuphine has been used.

Head Injury and Increased Intracranial Pressure

The possible respiratory depressant effects and the potential of potent analgesics to elevate cerebrospinal fluid pressure (resulting from vasodilation following CO2 retention) may be markedly exaggerated in the presence of head injury, intracranial lesions or a pre-existing increase in intracranial pressure. Furthermore, potent analgesics can produce effects which may obscure the clinical course of patients with head injuries. Therefore, Nalbuphine hydrochloride injection should be used in these circumstances only when essential, and then should be administered with extreme caution.

Interaction With Other Central Nervous System Depressants

Although Nalbuphine possesses opioid antagonist activity, there is evidence that in nondependent patients it will not antagonize an opioid analgesic administered just before, concurrently, or just after an injection of Nalbuphine hydrochloride. Therefore, patients receiving an opioid analgesic, general anesthetics, phenothiazines, or other tranquilizers, sedatives, hypnotics, or other CNS depressants (including alcohol) concomitantly with Nalbuphine may exhibit an additive effect. When such combined therapy is contemplated, the dose of one or both agents should be reduced.

Precautions

General

Impaired Respiration: At the usual adult dose of 10 mg/70 kg, Nalbuphine hydrochloride causes some respiratory depression approximately equal to that produced by equal doses of morphine. However, in contrast to morphine, respiratory depression is not appreciably increased with higher doses of Nalbuphine. Respiratory depression induced by Nalbuphine can be reversed by naloxone hydrochloride when indicated. Nalbuphine hydrochloride injection should be administered with caution at low doses to patients with impaired respiration (e.g., from other medication, uremia, bronchial asthma, severe infection, cyanosis or respiratory obstructions).

Impaired Renal or Hepatic Function: Because Nalbuphine is metabolized in the liver and excreted by the kidneys, Nalbuphine hydrochloride should be used with caution in patients with renal or liver dysfunction and administered in reduced amounts.

Myocardial Infarction: As with all potent analgesics, Nalbuphine hydrochloride should be used with caution in patients with myocardial infarction who have nausea or vomiting.

Biliary Tract Surgery: As with all opioid analgesics, Nalbuphine hydrochloride should be used with caution in patients about to undergo surgery of the biliary tract since it may cause spasm of the sphincter of Oddi.

Cardiovascular System: During evaluation of Nalbuphine hydrochloride injection, in anesthesia, a higher incidence of bradycardia has been reported in patients who did not receive atropine pre-operatively.

Information for Patients

Patients should be advised of the following information:

• 
  

  Nalbuphine is associated with sedation and may impair mental and physical abilities required for the performance of potentially dangerous tasks such as driving a car or operating machinery.

  
  


• 
  

  Nalbuphine is to be used as prescribed by a physician. Dose or frequency should not be increased without first consulting with a physician since Nalbuphine may cause psychological or physical dependence.

  
  


• 
  

  The use of Nalbuphine with other opioids can cause signs and symptoms of withdrawal.

  
  


• 
  

  Abrupt discontinuation of Nalbuphine after prolonged usage may cause signs and symptoms of withdrawal.

  
  

Laboratory Tests

Nalbuphine hydrochloride may interfere with enzymatic methods for the detection of opioids depending on the specificity/sensitivity of the test. Consult the test manufacturer for specific details.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis: Long term carcinogenicity studies were performed in rats (24 months) and mice (19 months) by oral administration at doses up to 200 mg/kg (1180 mg/m2) and 200 mg/kg (600 mg/m2) per day, respectively. There was no evidence of an increase in tumors in either species related to Nalbuphine hydrochloride administration. The maximum recommend human dose (MRHD) in a day is 160 mg subcutaneously, intramuscularly or intravenously, or approximately 100 mg/m2/day for a 60 kg subject.

Mutagenesis: Nalbuphine hydrochloride did not have mutagenic activity in the AMES test with four bacterial strains, in the Chinese Hamster Ovary HGPRT assays or in the Sister Chromatids Exchange Assay. However, Nalbuphine hydrochloride induced an increased frequency of mutation in the mouse lymphoma assay. Clastogenic activity was not observed in the mouse micronucleus test of the cytogenicity bone marrow assay in rats.

Impairment of Fertility: A reproduction study was performed in male and female rats at subcutaneous doses up to 56 mg/kg/day or 330 mg/m2/day. Nalbuphine hydrochloride did not affect either male or female fertility rats.

Usage in Pregnancy

Teratogenic Effects:

Pregnancy Category B: Reproduction studies have been performed in rats by subcutaneous administration of Nalbuphine up to 100 mg/kg/day, or 590 mg/m2/day which is approximately 6 times the MRHD, and in rabbits by intravenous administration of Nalbuphine up to 32 mg/kg/day, or 378 mg/m2/day which is approximately 4 times the MRHD. The results did not reveal evidence of developmental toxicity, including teratogenicity, or harm to the fetus. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Non-teratogenenic Effects:

Neonatal body weight and survival rates were reduced at birth and during lactation when Nalbuphine was subcutaneously administered to female and male rats prior to mating and throughout gestation and lactation or to pregnant rats during the last third of gestation and throughout lactation at doses approximately 4 times the maximum recommended human dose.

Use During Labor and Delivery

See WARNINGS.

Nursing Mothers

Limited data suggest that Nalbuphine hydrochloride is excreted in maternal milk but only in a small amount (less than 1% of the administered dose) and with a clinically insignificant effect. Caution should be exercised when Nalbuphine hydrochloride is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 18 years have not been established.

Adverse Reactions

The most frequent adverse reaction in 1066 patients treated with Nalbuphine hydrochloride injection was sedation 381 (36%). Less frequent reactions were: sweaty/clammy 99 (9%), nausea/vomiting 68 (6%), dizziness/vertigo 58 (5%), dry mouth 44 (4%), and headache 27 (3%).

Other adverse reactions which occurred (reported incidence of 1% or less) were:

CNS Effects: Nervousness, depression, restlessness, crying, euphoria, floating, hostility, unusual dreams, confusion, faintness, hallucinations, dysphoria, feeling of heaviness, numbness, tingling, unreality. The incidence of psychotomimetic effects, such as unreality, depersonalization, delusions, dysphoria and hallucinations has been shown to be less than that which occurs with pentazocine.

Cardiovascular: Hypertension, hypotension, bradycardia, tachycardia.

Gastrointestinal: Cramps, dyspepsia, bitter taste.

Respiratory: Depression, dyspnea, asthma.

Dermatologic: Itching, burning, urticaria.

Miscellaneous: Speech difficulty, urinary urgency, blurred vision, flushing and warmth.

Allergic Reactions: Anaphylactic/anaphylactoid and other serious hypersensitivity reactions have been reported following the use of Nalbuphine and may require immediate, supportive medical treatment. These reactions may include shock, respiratory distress, respiratory arrest, bradycardia, cardiac arrest, hypotension, or laryngeal edema. Some of these allergic reactions may be life-threatening. Other allergic-type reactions reported include stridor, bronchospasm, wheezing, edema, rash, pruritus, nausea, vomiting, diaphoresis, weakness, and shakiness.

Events Observed during Post-marketing Surveillance of Nalbuphine Hydrochloride Injection

Due to the nature and limitations of spontaneous reporting, causality has not been established for the following adverse events received for Nalbuphine hydrochloride injection: abdominal pain, pyrexia, depressed level or loss of consciousness, somnolence, tremor, anxiety, pulmonary edema, agitation, seizures, and injection site reactions such as pain, swelling, redness, burning, and hot sensations. Death has been reported from severe allergic reactions to Nalbuphine hydrochloride treatment. Fetal death has been reported where mothers received Nalbuphine hydrochloride during labor and delivery.

Drug Abuse and Dependence

There have been reports of abuse and dependence associated with Nalbuphine hydrochloride among health care providers, patients and bodybuilders. There have been reported instances of psychological and physical dependence and tolerance in patients abusing Nalbuphine hydrochloride. Individuals with a prior history of opioid or other substance abuse or dependence may be at greater risk in responding to reinforcing properties of Nalbuphine hydrochloride.

Abrupt discontinuation of Nalbuphine hydrochloride following prolonged use has been followed by symptoms of opioid withdrawal, i.e., abdominal cramps, nausea and vomiting, rhinorrhea, lacrimation, restlessness, anxiety, elevated temperature and piloerection.

Overdosage

The immediate intravenous administration of an opiate antagonist such as naloxone or nalmefene is a specific antidote. Oxygen, intravenous fluids, vasopressors and other supportive measures should be used as indicated.

The administration of single doses of 72 mg of Nalbuphine hydrochloride subcutaneously to eight normal subjects has been reported to have resulted primarily in symptoms of sleepiness and mild dysphoria.

Nalbuphine Dosage and Administration

The usual recommended adult dose is 10 mg for a 70 kg individual administered subcutaneously, intramuscularly, or intravenously; this dose may be repeated every 3 to 6 hours as necessary. Dosage should be adjusted according to the severity of the pain, physical status of the patient, and other medications which the patient may be receiving (see Interaction With Other Central Nervous System Depressants under WARNINGS). In nontolerant individuals, the recommended single maximum dose is 20 mg with a maximum total daily dose of 160 mg.

The use of Nalbuphine hydrochloride injection as a supplement to balanced anesthesia requires larger doses than those recommended for analgesia. Induction doses of Nalbuphine hydrochloride range from 0.3 mg/kg to 3 mg/kg intravenously to be administered over a 10 to 15 minute period with maintenance doses of 0.25 to 0.5 mg/kg in single intravenous administrations as required. The use of Nalbuphine hydrochloride injection may be followed by respiratory depression which can be reversed with the opioid antagonist naloxone hydrochloride.

Patients Dependent on Opioids: Patients who have been taking opioids chronically may experience withdrawal symptoms upon the administration of Nalbuphine hydrochloride injection. If unduly troublesome, opioid withdrawal symptoms can be controlled by the slow intravenous administration of small increments of morphine, until relief occurs. If the previous analgesic was morphine, meperidine, codeine, or other opioid with similar duration of activity, one-fourth of the anticipated dose of Nalbuphine hydrochloride can be administered initially and the patient observed for signs of withdrawal, i.e., abdominal cramps, nausea and vomiting, lacrimation, rhinorrhea, anxiety, restlessness, elevation of temperature or piloerection. If untoward symptoms do not occur, progressively larger doses may be tried at appropriate intervals until the desired level of analgesia is obtained with Nalbuphine hydrochloride.

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

How is Nalbuphine Supplied

Nalbuphine Hydrochloride Injection is supplied as follows:

NDC No.	Container	Size (mL)	mg/mL	Total mg
0409–1463–01	Ampul	1	10	10
0409–1465–01	Ampul	1	20	20
0409–1464–01	Fliptop Vial (multiple-dose)	10	10	100
0409–1467–01	Fliptop Vial (multiple-dose)	10	20	200

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

Protect from light. Store in carton until contents have been used.

Revised: August, 2007

 

Printed in USA                            EN - 1571

Hospira, Inc., Lake Forest, IL 60045 USA

RL-0188

RL-1219

RL-1643

RL-1220

Nalbuphine HYDROCHLORIDE  Nalbuphine hydrochloride  injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0409-1463 Route of Administration INTRAMUSCULAR, INTRAVENOUS, SUBCUTANEOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Nalbuphine HYDROCHLORIDE (Nalbuphine) Nalbuphine HYDROCHLORIDE 10 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength SODIUM CITRATE 0.47 mg  in 1 mL CITRIC ACID MONOHYDRATE 0.63 mg  in 1 mL SODIUM CHLORIDE   SODIUM HYDROXIDE   HYDROCHLORIC ACID

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0409-1463-01 10 AMPULE In 1 CARTON contains a AMPULE 1 1 mL In 1 AMPULE This package is contained within the CARTON (0409-1463-01) 2 0409-1463-49 10 AMPULE In 1 CARTON contains a AMPULE 2 1 mL In 1 AMPULE This package is contained within the CARTON (0409-1463-49) 3 0409-1463-61 10 AMPULE In 1 CARTON contains a AMPULE 3 1 mL In 1 AMPULE This package is contained within the CARTON (0409-1463-61)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA070914	08/22/2011

Nalbuphine HYDROCHLORIDE  Nalbuphine hydrochloride  injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0409-1464 Route of Administration INTRAMUSCULAR, INTRAVENOUS, SUBCUTANEOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Nalbuphine HYDROCHLORIDE (Nalbuphine) Nalbuphine HYDROCHLORIDE 10 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength SODIUM CITRATE 0.47 mg  in 1 mL CITRIC ACID MONOHYDRATE 0.63 mg  in 1 mL SODIUM CHLORIDE   SODIUM HYDROXIDE   HYDROCHLORIC ACID   METHYLPARABEN 1.8 mg  in 1 mL PROPYLPARABEN 0.2 mg  in 1 mL

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0409-1464-01 1 VIAL In 1 CARTON contains a VIAL, MULTI-DOSE 1 10 mL In 1 VIAL, MULTI-DOSE This package is contained within the CARTON (0409-1464-01) 2 0409-1464-49 1 VIAL In 1 CARTON contains a VIAL, MULTI-DOSE 2 10 mL In 1 VIAL, MULTI-DOSE This package is contained within the CARTON (0409-1464-49)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA070915	08/22/2011

Nalbuphine HYDROCHLORIDE  Nalbuphine hydrochloride  injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0409-1465 Route of Administration INTRAMUSCULAR, INTRAVENOUS, SUBCUTANEOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Nalbuphine HYDROCHLORIDE (Nalbuphine) Nalbuphine HYDROCHLORIDE 20 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength SODIUM CITRATE 0.47 mg  in 1 mL CITRIC ACID MONOHYDRATE 0.63 mg  in 1 mL SODIUM CHLORIDE   SODIUM HYDROXIDE   HYDROCHLORIC ACID

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0409-1465-01 10 AMPULE In 1 CARTON contains a AMPULE 1 1 mL In 1 AMPULE This package is contained within the CARTON (0409-1465-01) 2 0409-1465-49 10 AMPULE In 1 CARTON contains a AMPULE 2 1 mL In 1 AMPULE This package is contained within the CARTON (0409-1465-49) 3 0409-1465-61 10 AMPULE In 1 CARTON contains a AMPULE 3 1 mL In 1 AMPULE This package is contained within the CARTON (0409-1465-61)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA070916	08/22/2011

Nalbuphine HYDROCHLORIDE  Nalbuphine hydrochloride  injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0409-1467 Route of Administration INTRAMUSCULAR, INTRAVENOUS, SUBCUTANEOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Nalbuphine HYDROCHLORIDE (Nalbuphine) Nalbuphine HYDROCHLORIDE 20 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength SODIUM CITRATE 0.47 mg  in 1 mL CITRIC ACID MONOHYDRATE 0.63 mg  in 1 mL SODIUM CHLORIDE   SODIUM HYDROXIDE   HYDROCHLORIC ACID   METHYLPARABEN 1.8 mg  in 1 mL PROPYLPARABEN 0.2 mg  in 1 mL

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0409-1467-01 25 VIAL In 1 CARTON contains a VIAL, MULTI-DOSE 1 10 mL In 1 VIAL, MULTI-DOSE This package is contained within the CARTON (0409-1467-01) 2 0409-1467-49 25 VIAL In 1 CARTON contains a VIAL, MULTI-DOSE 2 10 mL In 1 VIAL, MULTI-DOSE This package is contained within the CARTON (0409-1467-49)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA070918	08/22/2011

Labeler - Hospira, Inc. (141588017)

Revised: 09/2011Hospira, Inc.

More Nalbuphine resources

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

• Nalbuphine MedFacts Consumer Leaflet (Wolters Kluwer)


• nalbuphine Concise Consumer Information (Cerner Multum)


• nalbuphine Injection Advanced Consumer (Micromedex) - Includes Dosage Information


• Nalbuphine Hydrochloride Monograph (AHFS DI)

Compare Nalbuphine with other medications

• Anesthesia
• Pain

Sterile Saline Diluent Tip-Lok Syringe

Generic Name: sodium chloride (Injection route)

SOE-dee-um KLOR-ide

Commonly used brand name(s)

In the U.S.

• Sterile Saline Diluent Tip-Lok Syringe


• Syrex

Available Dosage Forms:

• Solution

Therapeutic Class: Parenteral Electrolyte, Sodium

Uses For Sterile Saline Diluent Tip-Lok Syringe

Sodium chloride as a 20% solution is given by injection into the uterus to cause abortion. It is to be administered only by or under the immediate care of your doctor.

Before Using Sterile Saline Diluent Tip-Lok Syringe

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

Allergies

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

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	C	Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

Studies in women suggest that this medication poses minimal risk to the infant when used during 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. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

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

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Bleeding problems or

• Epilepsy or

• Heart or blood vessel disease or

• High blood pressure (hypertension) or

• Kidney disease—Sodium chloride injection may make these conditions worse or increase the chance of side effects occurring

• Fibroid tumors of the uterus—Large fibroid tumors may cause a problem with injecting sodium chloride into the uterus. Special injection precautions can be taken by the doctor if he knows that you have this type of tumor

• Previous major surgery of the uterus, including a cesarean—Scars in the uterus from any previous surgery of the uterus may increase the chance of medical problems occurring. Special precautions can be taken by the doctor to prevent problems from occurring

Proper Use of sodium chloride

This section provides information on the proper use of a number of products that contain sodium chloride. It may not be specific to Sterile Saline Diluent Tip-Lok Syringe. Please read with care.

During the procedure, you will be awake and asked questions about how you are doing by the health care team. This helps them to react quickly to any problems you might have and to keep side effects to a minimum.

Dosing

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

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

Precautions While Using Sterile Saline Diluent Tip-Lok Syringe

Do not have sexual intercourse and avoid using tampons or douches for 2 to 3 weeks after the abortion to allow your body time to heal. This will also help protect you from getting an infection of the vagina or uterus.

Spotting (or slight bleeding from the uterus) is normal after the abortion. This may continue for 2 weeks. Heavier spotting or uterine bleeding should be reported to your health care professional.

Contraception should be considered for the near future because you may ovulate before your first menstrual period. Your first menstrual period will occur 4 to 6 weeks after the abortion.

Sterile Saline Diluent Tip-Lok Syringe 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:

Less common

• Excessive blood loss


• fever

Rare

• Anxiety


• burning pain in lower abdomen


• chest pain, severe


• chills


• confusion


• convulsions (seizures)


• coughing


• dizziness


• feeling of heat


• feeling of warmth in lips and tongue


• headache (severe or dull)


• nervousness


• numbness of the fingertips


• pain in lower back, pelvis, or stomach


• ringing in the ears


• shortness of breath


• sweating


• thirst (sudden) or salty taste


• unconsciousness


• vision problems


• weakness

After the procedure is completed, some side effects may occur that need medical attention. Check with your doctor if you notice any of the following side effects:

• Abdominal cramping


• bad smelling discharge from vagina


• bleeding at place of injection


• chills or shivering


• fever


• increase in bleeding from the uterus


• pain in lower abdomen


• passing of pieces of tissue from the uterus


• redness at place of injection

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.

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.

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More Sterile Saline Diluent Tip-Lok Syringe resources

• Sterile Saline Diluent Tip-Lok Syringe Drug Interactions
• Sterile Saline Diluent Tip-Lok Syringe Support Group
• 0 Reviews for Sterile Saline Diluent Tip-Lok Syringe - Add your own review/rating

Compare Sterile Saline Diluent Tip-Lok Syringe with other medications

• Postural Orthostatic Tachycardia Syndrome

Septocaine

Generic Name: Articaine Hydrochloride
Class: Local Anesthetics
Chemical Name: 4-Methyl-3-[[1-oxo-2-(propylamino)propyl]amino]-2-thiopenecarboxylic acid methyl ester monohydrochloride
Molecular Formula: C₁₃H₂₀N₂O₃S•HCl
CAS Number: 23964-57-0

Introduction

Intermediate-acting local anesthetic (amide type).^{1 2 3 4}

Uses for Septocaine

Dental Anesthesia

Local, infiltrative, or regional (i.e., nerve block) anesthesia in simple and complex dental and periodontal procedures.^{1 8}

Anesthetic activity comparable to that of lidocaine, mepivacaine, and prilocaine.^{2 4 7}

Septocaine Dosage and Administration

General

• 
  

  Determine dosage based on type and extent of surgical procedure, depth of anesthesia, degree of muscular relaxation, and condition of the patient.¹ Use smallest dose required to produce the desired effect.¹

  
  


• 
  

  For pediatric patients, determine dosage based on age, weight, physical condition of the patient, and type and extent of surgical procedure.¹

  
  

Administration

Submucosal Injection

For solution and drug compatibility information, see Compatibility under Stability.

Administer by submucosal infiltration or by nerve block.¹

Aspirate prior to administration to guard against intravascular injection.¹

For chemical disinfection of the cartridge unit, use isopropyl (rubbing) alcohol (91%) or ethyl alcohol (70%).¹ Do not use brands that are not of USP grade, since these preparations may contain denaturants that may be injurious to rubber.¹

Dosage

Available as fixed combination containing articaine hydrochloride and epinephrine bitartrate; dosage expressed in terms of articaine hydrochloride.¹

Pediatric Patients

Dental Anesthesia

Submucosal Injection

Children ≥4 years of age: Use lower dosages than those suggested for healthy adults (see Adults under Dosage and Administration).¹

Simple procedures: 0.76–5.65 mg/kg used in clinical trials.¹

Complex procedures: 0.37–7.48 mg/kg used in clinical trials.¹

Approximately 13% of pediatric patients in clinical trials required additional injections for complete anesthesia.¹

Adults

Dental Anesthesia

Submucosal Injection

Usual dosage range: 20–204 mg.¹

Recommended Dosages (as articaine hydrochloride 4% with epinephrine 1:100,000) for Dental Anesthesia in Healthy Adults1

Procedure	Volume of Injection (mL)	Total Dose of Articaine Hydrochloride (mg)
Infiltration	0.5–2.5	20–100
Nerve block	0.5–3.4	20–136
Oral surgery	1–5.1	40–204

Prescribing Limits

Pediatric Patients

Dental Anesthesia

Submucosal Injection

Maximum 7 mg/kg (0.175 mL/kg).¹

Adults

Dental Anesthesia

Submucosal Injection

Maximum 7 mg/kg (0.175 mL/kg).¹

Special Populations

Hepatic Impairment

Reduce dosage in patients with hepatic disease.¹

Geriatric Patients

Reduce dosage in patients ≥65 years of age.¹

Patients 65–74 Years of Age

Simple procedures: 0.43–4.76 mg/kg used in clinical trials.¹

Complex procedures: 1.05–4.27 mg/kg used in clinical trials.¹

Approximately 6% of patients in clinical trials required additional injections for complete anesthesia.¹

Patients ≥75 Years of Age

Simple procedures: 0.78–4.76 mg/kg used in clinical trials.¹

Complex procedures: 1.12–2.17 mg/kg used in clinical trials.¹

None of the patients in clinical trials required additional injections for complete anesthesia.¹

Other Populations

Reduce dosage in patients with cardiac disease, debilitated patients, and patients with acute illnesses.¹

Cautions for Septocaine

Contraindications

• 
  

  Known hypersensitivity to local anesthetics of the amide type or to sodium metabisulfite.^{1 4}

  
  

Warnings/Precautions

Warnings

Epinephrine Administration

Injection contains epinephrine, which may cause tissue necrosis or systemic toxicity.¹ Consider usual precautions associated with epinephrine administration.¹

Accidental Intravascular Injection

Accidental intravascular injection may result in confusion, seizures, CNS or cardiorespiratory depression, coma, and/or respiratory arrest.¹

Aspirate prior to administration to guard against intravascular injection.¹

Should be used only by clinicians who are sufficiently knowledgeable in the diagnosis and management of dose-related toxicity and other acute emergencies that might arise.¹ Resuscitative equipment and drugs must be available for immediate use.¹

Sensitivity Reactions

Sulfite Sensitivity

Articaine injection contains sodium metabisulfite, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.¹

General Precautions

CNS Effects

Toxic plasma concentrations of local anesthetics (resulting from systemic absorption) associated with adverse CNS effects (e.g., restlessness, anxiety, tinnitus, lightheadedness, dizziness, disorientation, excitement, blurred vision, tremors, depression, drowsiness).^{1 3}

Carefully monitor level of consciousness after each local anesthetic injection.¹

Cardiovascular Effects

Toxic plasma concentrations of local anesthetics (resulting from systemic absorption) associated with adverse cardiovascular effects (e.g., reduced myocardial contractility, peripheral vasodilation, depressed cardiac conduction and excitability).¹ Possible atrioventricular block, ventricular arrhythmia, cardiac arrest, and, rarely, death.¹ Carefully monitor cardiovascular and respiratory vital signs after each local anesthetic injection.¹

Cardiac arrhythmias may occur in patients receiving potent general anesthetics; use with caution in such patients.¹

Articaine hydrochloride injection contains epinephrine; risk of exaggerated vasoconstrictor response in patients with hypertension or peripheral vascular disease.¹ Risk of ischemic injury or necrosis.¹

Use with caution in patients with heart block or other cardiovascular disease.¹

Specific Populations

Pregnancy

Category C.¹

Lactation

Not known whether articaine or its metabolites are distributed into milk.^{1 4} Caution advised if used in nursing women.¹

Pediatric Use

Safety and efficacy not established in children <4 years of age.^{1 4}

Geriatric Use

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

Hepatic Impairment

Not studied in patients with hepatic impairment.¹ Use with caution in patients with severe hepatic impairment.¹

Common Adverse Effects

Pain,^{1 2 4 7} headache,^{1 2 4 7} facial edema,^{1 2 4} gingivitis,^{1 2 4} paresthesia,^{1 2 4} infection.^{1 2 4}

Interactions for Septocaine

Approximately 5–10% of available articaine is metabolized by CYP enzymes.^{1 3}

Specific Drugs

Drug	Interaction	Comments
Anesthetics, general	Possible cardiac arrhythmias when articaine is administered during or following administration of potent general anesthetics1	Use with caution1
Antidepressants, tricyclics	Possible severe, prolonged hypertension due to epinephrine component1	Avoid concomitant use;1 if must be used concomitantly, careful monitoring is required1
Butyrophenones	Possible reduction or reversal of pressor effect of epinephrine1	Avoid concomitant use;1 if must be used concomitantly, careful monitoring is required 1
MAO inhibitors	Possible severe, prolonged hypertension due to epinephrine component1	Avoid concomitant use;1 if must be used concomitantly, careful monitoring is required1
Phenothiazines	Possible reduction or reversal of pressor effect of epinephrine1	Avoid concomitant use;1 if must be used concomitantly, careful monitoring is required1

Septocaine Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentrations achieved approximately 25 minutes following single dose and 48 minutes following 3 doses.¹

Onset

1–6 minutes following submucosal injection.¹ Average onset of anesthesia following articaine administration appears to be similar to that of prilocaine^{5 6 8} but slightly faster than that of other local anesthetics (e.g., lidocaine).^{3 5 8}

Duration

Complete anesthesia lasts approximately 1 hour.¹

Distribution

Plasma Protein Binding

Approximately 60–80% (albumin and γ-globulins).¹

Elimination

Metabolism

Systemically absorbed articaine is rapidly metabolized by plasma carboxyesterase to articainic acid (inactive);¹ approximately 5–10% of available articaine is metabolized to articainic acid by CYP enzymes.^{1 3}

Elimination Route

Excreted principally in urine as inactive metabolites and small amounts (2%) of unchanged drug;^{1 4} approximately 53–57% of administered dose excreted within 24 hours following submucosal administration.¹

Half-life

Approximately 1.8 hours.¹

Stability

Storage

Parenteral

Injection

25°C (may be exposed to 15–30°C).¹ Protect from light.¹

Compatibility

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

May be incompatible with strong oxidizing agents.^a

ActionsActions

• 
  

  Local anesthetics block the generation and conduction of nerve impulses by increasing the threshold for electrical excitation, slowing the propagation of the nerve impulse, and reducing the rate of rise of the action potential.¹

  
  


• 
  

  Formulated with epinephrine to decrease articaine's rate and extent of systemic absorption and to prolong its duration of action.^{1 4}

  
  


• 
  

  Has intermediate duration of action (approximately 1 hour).^{1 2 3 4}

  
  

Advice to Patients

• 
  

  Prior to administration, advise patients of the possibility of temporary loss of sensation and muscle function following infiltration and nerve block injections.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., cardiovascular disease).¹

  
  


• 
  

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

  
  


• 
  

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

  
  

Preparations

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

Articaine Hydrochloride

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection	4% with Epinephrine Bitartrate 1:100,000 (of epinephrine)	Septocaine (with sodium metabisulfite)	Septodont

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 May 2004. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Septodont, Inc. Septocaine (articaine hydrochloride 4% with epinephrine 1:100,000) injection prescribing information. New Castle, DE; 2000 Apr.

2. Malamed SF, Gagnon S, Leblanc D. Efficacy of articaine: a new amide local anesthetic. J Am Dent Assoc. 2000; 131:635-42. [IDIS 448169] [PubMed 10832257]

3. Oertel R, Rahn R, Kirch W. Clinical pharmacokinetics of articaine. Clin Pharmacokinet. 1997; 33:417-25. [PubMed 9435991]

4. Malamed SF, Gagnon S, Leblanc D. Articaine hydrochloride: a study of the safety of a new amide local anesthetic. J Am Dent Assoc. 2001; 132:177-85. [IDIS 466889] [PubMed 11217590]

5. Simon MAM, Gielen MJM, Alberink N et al. Intravenous regional anesthesia with 0.5% articaine, 0.5% lidocaine, or 0.5% prilocaine. Reg Anesth. 1997; 22:29-34. [PubMed 9010944]

6. Pitkanen MT, Xu M, Haasio J et al. Comparison of 0.5% articaine and 0.5% prilocaine in intravenous regional anesthesia of the arm: a cross-over study in volunteers. Reg Anesth Pain. 1999; 24:131-5.

7. Malamed SF, Gagnon S, Leblanc D et al. A comparison between articaine HCl and lidocaine HCl in pediatric dental patients. Pediatr Dent. 2000; 22:307-11. [PubMed 10969438]

8. Septodont Inc., New Castle, DE: Personal communication.

a. Septodont, Inc. Septocaine (articaine hydrochloride) injection material safety data sheet. New Castle, DE; 2002 Jul.

More Septocaine resources

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

• Septocaine Prescribing Information (FDA)


• Septocaine Concise Consumer Information (Cerner Multum)

Compare Septocaine with other medications

• Anesthesia
• Local Anesthesia

Kutrase

Generic Name: pancrelipase (oral) (pan kre LYE pace)

Brand Names: Cotazym, Creon, Dygase, Ku-Zyme, Ku-Zyme HP, Kutrase, Lapase, Palcaps 10, Pancrease MT 10, Pancrease MT 16, Pancrease MT 20, Pancrease MT 4, Pancrecarb MS-16, Pancrecarb MS-4, Pancrecarb MS-8, Panocaps, Panocaps MT 16, Ultrase, Ultrase MT 12, Ultrase MT 18, Ultrase MT 20, Viokase, Viokase 16, Zenpep

What is pancrelipase?

Pancrelipase is a combination of three enzymes (proteins): lipase, protease, and amylase. These enzymes are normally produced by the pancreas and are important in the digestion of fats, proteins, and sugars.

Pancrelipase is used to replace these enzymes when the body does not have enough of its own. Certain medical conditions can cause this lack of enzymes, including cystic fibrosis, chronic inflammation of the pancreas, or blockage of the pancreatic ducts.

Pancrelipase may also be used following surgical removal of the pancreas.

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

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

You should not take pancrelipase if you are allergic to pork proteins.

Before taking pancrelipase, tell your doctor if you have gout, kidney disease, a history of intestinal blockage, a sudden onset of pancreatitis, or worsening of chronic pancreatic disease.

Use pancrelipase regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

Do not hold the tablets or capsule contents in your mouth. The medication may irritate the inside of your mouth.

Do not inhale the powder from a pancrelipase capsule, or allow it to touch your skin. It may cause irritation, especially to your nose and lungs.

If you miss a dose of this medicine, skip the missed dose and wait until your next scheduled dose to take the medicine. Do not take extra medicine to make up the missed dose.

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

You should not take pancrelipase if you are allergic to pork proteins.

If you have any of these other conditions, you may need a pancrelipase dose adjustment or special tests:

• kidney disease;


• 
  

  gout;

  
  


• 
  

  a history of blockage in your intestines;

  
  


• 
  

  a sudden onset of pancreatitis; or

  
  


• 
  

  worsening of chronic pancreatic disease.

  
  

This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether pancrelipase passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take pancrelipase?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Pancrelipase should be taken with a meal or snack. Take the medicine with a full glass of water or juice.

Do not hold the tablets or capsule contents in your mouth. The medication may irritate the inside of your mouth.

Do not crush, chew, break, or open an extended-release tablet or capsule. Swallow it whole. Breaking or opening the pill may cause too much of the drug to be released at one time.

You may open the pancrelipase capsule and sprinkle the medicine into a spoonful of pudding or applesauce to make swallowing easier. Swallow right away without chewing. Do not save the mixture for later use. Discard the empty capsule.

Do not inhale the powder from a pancrelipase capsule, or allow it to touch your skin. It may cause irritation, especially to your nose and lungs.

Use pancrelipase regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

Store in the original container at room temperature (below 78 degrees F) for up to 12 weeks. Protect from moisture or high heat. Keep the bottle tightly closed when not in use. If the medication is exposed to temperatures between 78 and 104 degrees F, throw it away after 30 days. Do not use any pancrelipase that has been exposed to temperatures above 104 degrees F.

What happens if I miss a dose?

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 diarrhea or stomach upset.

What should I avoid while taking pancrelipase?

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Pancrelipase 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. Call your doctor at once if you have severe or unusual stomach pain. This could be a symptom of a rare but serious bowel disorder.

Less serious side effects may include:

• 
  

  nausea or vomiting;

  
  


• 
  

  mild stomach pain or upset;

  
  


• 
  

  diarrhea or constipation;

  
  


• 
  

  bloating or gas.

  
  


• 
  

  greasy stools;

  
  


• 
  

  rectal irritation;

  
  


• 
  

  headache, dizziness;

  
  


• 
  

  cough; or

  
  


• 
  

  weight loss.

  
  

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 pancrelipase?

There may be other drugs that can interact with pancrelipase. 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 Kutrase resources

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

• Pancrelipase Professional Patient Advice (Wolters Kluwer)


• Pancrelipase Prescribing Information (FDA)


• Pancrelipase Monograph (AHFS DI)


• Pancrelipase MedFacts Consumer Leaflet (Wolters Kluwer)


• Creon Prescribing Information (FDA)


• Creon Advanced Consumer (Micromedex) - Includes Dosage Information


• Creon MedFacts Consumer Leaflet (Wolters Kluwer)


• Creon Consumer Overview


• Creon 10 Delayed-Release Capsules MedFacts Consumer Leaflet (Wolters Kluwer)


• Dygase MedFacts Consumer Leaflet (Wolters Kluwer)


• Pancreaze Consumer Overview


• Pancreaze Prescribing Information (FDA)


• Zenpep Prescribing Information (FDA)


• Zenpep Consumer Overview

Compare Kutrase with other medications

• Chronic Pancreatitis
• Cystic Fibrosis
• Pancreatic Exocrine Dysfunction

Where can I get more information?

• Your pharmacist can provide more information about pancrelipase.

See also: Kutrase side effects (in more detail)

Simvastatin

Class: HMG-CoA Reductase Inhibitors
VA Class: CV350
Chemical Name: [1S-[1α,3α,7β,8β(2S*,4S*)8aβ-2,2-Dimethybutanoic acid 1,2,3,7,8,8a - hexahydro - 3,7 - dimethyl - 8 - [2 - (tetrahydro - 4 - hydroxy - 6 - oxo - 2H - pyran - 2 - yl)ethyl] - 1 - naphthalenyl ester
Molecular Formula: C₂₅H₃₈O₅
CAS Number: 79902-63-9
Brands: Vytorin, Zocor

Special Alerts:

[Posted 06/08/2011] ISSUE: FDA notified healthcare professionals that it is recommending limiting the use of the highest approved dose of the cholesterol-lowering medication simvastatin (80 mg) [Zocor] because of increased risk of muscle damage. Patients taking simvastatin 80 mg daily have an increased risk of myopathy compared to patients taking lower doses of this drug or other drugs in the same class. This risk appears to be higher during the first year of treatment, is often the result of interactions with certain medicines, and is frequently associated with a genetic predisposition toward simvastatin-related myopathy. The most serious form of myopathy, called rhabdomyolysis, can damage the kidneys and lead to kidney failure which can be fatal. FDA is requiring changes to the simvastatin label to add new contraindications (should not be used with certain medications) and dose limitations for using simvastatin with certain medicines.

BACKGROUND: The new changes to the drug labels for simvastatin-containing medicines are based on FDA’s review of the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) trial and other data described in the Agency’s March 2010 Ongoing safety review of high-dose Zocor (simvastatin) and increased risk of muscle injury. Simvastatin 80 mg should be used only in patients who have been taking this dose for 12 months or more without evidence of muscle injury (myopathy).

RECOMMENDATION: Simvastatin 80 mg should not be started in new patients, including patients already taking lower doses of the drug. For more information visit the FDA website at: and .

Introduction

Antilipemic agent; hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor (i.e., statin).^{1 2 3 4 5}

Uses for Simvastatin

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

Prevention of Cardiovascular Events

Adjunct to dietary therapy in patients with CHD or CHD risk equivalents (e.g., diabetes mellitus, peripheral arterial disease, history of stroke or other cerebrovascular disease) to reduce the risk of total mortality by reducing CHD death, to reduce the risk of nonfatal MI and stroke, and to reduce the need for coronary and non-coronary revascularization procedures.¹

Slowing progression or inducing regression of atherosclerosis† in coronary arteries by reducing intimal-medial wall thickness.^{1 48 51 53}

Dyslipidemias

Adjunct to dietary therapy in adults 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 and mixed dyslipidemia, including heterozygous familial hypercholesterolemia and other causes of hypercholesterolemia (e.g., polygenic hypercholesterolemia).^{1 3 4 18} May be used in combination or fixed combination with ezetimibe (as Vytorin tablets) for additive antilipemic effects.^{88 89}

Adjunct to dietary therapy to decrease elevated serum total cholesterol, LDL-cholesterol, and apo B concentrations in the management of heterozygous familial hypercholesterolemia in boys and girls (≥1 year postmenarche) ≥10 years of age who have a serum LDL-cholesterol concentration of ≥190 mg/dL or in those who have a serum LDL-cholesterol concentration of ≥160 mg/dL and either a family history of premature cardiovascular disease or ≥2 cardiovascular risk factors despite an adequate trial of dietary management.¹

Reduction of elevated serum total and LDL-cholesterol concentrations in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering therapies (e.g., plasma LDL-apheresis) or when such therapies are not available.¹ May be used in combination or fixed combination with ezetimibe (as Vytorin tablets) for additive antilipemic effects.^{88 89}

Adjunct to dietary therapy to decrease elevated serum triglyceride and VLDL-cholesterol concentrations in the management of primary dysbetalipoproteinemia.¹

Adjunct to dietary therapy to decrease elevated serum triglyceride concentrations in the management of hypertriglyceridemia.¹

Reduction of total and LDL-cholesterol concentrations in patients with hypercholesterolemia associated with or exacerbated by diabetes mellitus† (diabetic dyslipidemia),^{13 55 58 59 74} cardiac†⁷⁶ or renal† transplantation,⁷⁷ or nephrotic syndrome†.^{63 64}

Simvastatin Dosage and Administration

General

• 
  

  Patients should be placed on a standard lipid-lowering diet before initiation of simvastatin therapy and should remain on this diet during treatment with the drug;¹ in patients with CHD or CHD risk equivalents, initiate simvastatin simultaneously with dietary management.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.

Administration

Oral Administration

Administer orally in the evening without regard to meals.^{1 2 3 4}

Administer simvastatin-ezetimibe fixed-combination preparation (Vytorin) orally in the evening without regard to meals.⁸⁸

Dosage

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

Pediatric Patients

Dyslipidemias

Oral

Children ≥10 years of age: 10 mg once daily.¹

Adjust dosage at intervals of ≥4 weeks until the desired effect on lipoprotein concentrations is observed.¹ Usual dosage range is 10–40 mg daily.¹

Adults

Dyslipidemias and Prevention of Cardiovascular Events

Oral

Initially, 20–40 mg once daily.¹

Patients with CHD or CHD risk equivalents: Initially, 40 mg once daily.¹

Adjust dosage at intervals of no less than 4 weeks until the desired effect on lipoprotein concentrations is observed.¹ Usual dosage range is 5–80 mg daily.¹

Simvastatin-ezetimibe fixed combination (Vytorin): Initially, simvastatin 20 mg and ezetimibe 10 mg once daily in the evening.⁸⁸ In patients requiring less aggressive LDL-cholesterol lowering, consider lower dosage (simvastatin 10 mg and ezetimibe 10 mg once daily).⁸⁸ In patients requiring LDL-cholesterol reductions >55%, give simvastatin 40 mg and ezetimibe 10 mg once daily.⁸⁸ Determine serum lipoprotein concentrations 2 weeks after initiation of therapy and adjust dosage as needed.⁸⁸ Usual maintenance dosage is simvastatin 10–80 mg and ezetimibe 10 mg once daily.⁸⁸

Risk of myopathy may be increased with use of higher simvastatin dosages (e.g., 80 mg daily).^{87 95 96} (See Musculoskeletal Effects under Cautions.)

Homozygous Familial Hypercholesterolemia

Oral

40 mg once daily in the evening or 80 mg daily in 3 divided doses of 20 mg, 20 mg, and an evening dose of 40 mg.¹

Simvastatin-ezetimibe fixed combination (Vytorin): Initially, simvastatin 40 or 80 mg and ezetimibe 10 mg once daily in the evening.⁸⁸

Risk of myopathy may be increased with use of higher simvastatin dosages (e.g., 80 mg daily).^{87 95 96} (See Musculoskeletal Effects under Cautions.)

Prescribing Limits

Pediatric Patients

Oral

Children ≥10 years of age: Maximum 40 mg once daily.¹

Special Populations

Hepatic Impairment

Use with caution in patients who consume substantial amounts of alcohol and/or have a history of liver disease.¹ Contraindicated in patients with active liver disease or unexplained, persistent increases in serum aminotransferase concentrations.¹

Renal Impairment

Dosage modification is not necessary in patients with mild to moderate impairment.¹ In patients with severe renal impairment, initially, 5 mg once daily.¹ Use with caution; monitor closely.¹

Simvastatin-ezetimibe fixed combination (Vytorin): Dosage modification is not necessary in patients with mild to moderate impairment.⁸⁸ In patients with severe renal impairment, do not use unless patient already has tolerated treatment with simvastatin at dosage of ≥5 mg daily; in such patients, exercise caution and monitor closely.⁸⁸

Cautions for Simvastatin

Contraindications

• 
  

  Active liver disease or unexplained, persistent elevations of serum aminotransferases.¹

  
  


• 
  

  Pregnancy or lactation.¹ Administer to women of childbearing age only when such patients are highly unlikely to conceive and have been informed of the potential hazards.¹

  
  


• 
  

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

  
  

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

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

Administer to women of childbearing age only when such patients are highly unlikely to conceive and have been informed of the potential hazards.¹ If the patient becomes pregnant while taking the drug, discontinue therapy and apprise the patient of the potential hazard to the fetus.¹

Hepatic Effects

Associated with increases in serum aminotransferase (AST, ALT) concentrations.¹

Pancreatitis,¹ hepatitis,¹ jaundice,¹ increased serum alkaline phosphatase concentrations,¹ and increased serum γ-glutamyl transpeptidase concentrations¹ have been reported.¹

Perform liver function tests before initiation of therapy and thereafter when clinically indicated.¹ In patients being titrated to a dosage of 80 mg daily, perform an additional liver function test prior to titration, at 3 months after titration, and periodically (e.g., semiannually) thereafter for the first year of treatment.¹

Patients who develop increased serum AST/ALT concentrations or manifestations of liver disease should be monitored with a second liver function evaluation to confirm the finding and should receive frequent liver function tests thereafter until the abnormalities return to normal.¹ If increases in AST or ALT concentrations of 3 times the ULN or higher persist, discontinue therapy.¹

The National Lipid Association (NLA) statin safety assessment task force recommends that clinicians be alert to signs and symptoms of hepatotoxicity (e.g., jaundice, malaise, fatigue, lethargy, hepatomegaly, increased indirect bilirubin concentrations, elevated PT). If substantial hepatotoxicity is suspected, discontinue therapy, determine etiology, and refer patient to a gastroenterologist or hepatologist if indicated.

Musculoskeletal Effects

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

Myopathy (manifested as muscle pain, tenderness, or weakness and serum CK (CPK) concentration increases >10 times the ULN) reported occasionally.¹

Rhabdomyolysis (characterized by muscle pain or weakness with marked increases [>10 times the ULN] in serum CK concentrations and increases in S_cr [usually accompanied by brown urine and urinary myoglobinuria]) with or without acute renal failure secondary to myoglobinuria has been reported; rare fatalities have occurred.¹

Risk of myopathy increased in patients receiving higher doses of statins; in patients with multisystem disease (e.g., renal or hepatic impairment); in patients with concurrent serious infections or hypothyroidism; in patients (particularly women) of advanced age (especially >80 years of age); in patients with small body frame and frailty; and in patients undergoing surgery (i.e., during perioperative periods).¹ Risk also may be increased by concomitant administration of cyclosporine, danazol, niacin, fibric acid derivatives (e.g., gemfibrozil), macrolide anti-infectives (i.e., erythromycin, clarithromycin), telithromycin, certain antifungal azoles (i.e., itraconazole, ketoconazole), alcohol, HIV protease inhibitors, nefazodone, amiodarone, verapamil, diltiazem, and large quantities (>1 quart daily) of grapefruit juice.^{1 88 90 91 92 93} (See Interactions.)

Recent study findings have raised concerns about a potential increased risk of myopathy in patients receiving simvastatin 80 mg daily compared with those receiving 20 mg daily.^{95 96 99} FDA is continuing to investigate the relationship between high-dose simvastatin and muscle injury.⁹⁵ Patients currently receiving simvastatin 80 mg daily should continue to take the drug as prescribed unless otherwise instructed by a clinician.⁹⁵ FDA recommends that such patients review their medical history and current drug regimens with their clinician to determine whether treatment should be continued.⁹⁵

Measure baseline serum CK concentrations prior to initiation of therapy, particularly in patients at high risk of developing musculoskeletal toxicity (e.g., geriatric patients, black men, patients receiving concomitant therapy with myotoxic drugs).

Obtain serum CK concentrations and compare with baseline concentrations in patients presenting with musculoskeletal symptoms suggestive of myopathy; because hypothyroidism may be a predisposing factor, TSH concentrations also should be obtained in such patients.

Discontinue if myopathy is diagnosed or suspected.¹

Monitor patients weekly if myalgia (muscle pain, tenderness) is present with either no CK elevation or a moderate elevation (3–10 times the ULN) until manifestations improve; discontinue if manifestations worsen.

Dosage reduction or temporary discontinuance may be prudent in patients with muscle discomfort and/or weakness in the presence of progressive elevation of CK concentrations on serial measurements.

Temporarily withhold therapy a few days prior to elective major surgery and when any major medical or surgical condition supervenes.¹

General Precautions

Role as Adjunct Therapy

Prior to institution of antilipemic therapy, vigorously attempt to control serum cholesterol by appropriate dietary regimens, weight reduction, exercise, and treatment of any underlying disorder that might be the cause of lipid abnormality.¹

Renal Effects

NLA recommends performing renal function tests prior to initiating statin therapy; routine monitoring of S_cr and proteinuria is not necessary. If S_cr is elevated in the absence rhabdomyolysis, may continue therapy but dosage adjustment may be necessary per labeling recommendations. If unexpected proteinuria develops, determine etiology; may continue therapy but dosage adjustment may be necessary per labeling recommendations.

CNS Effects

CNS vascular lesions (e.g., perivascular hemorrhage and edema, mononuclear cell infiltration of perivascular spaces, perivascular fibrin deposits and necrosis of small vessels) observed in animals.¹

If manifestations of peripheral neuropathy occur, NLA recommends evaluating patient to rule out secondary causes (e.g., diabetes mellitus, renal impairment, alcohol abuse, vitamin B₁₂ deficiency, cancer, hypothyroidism, acquired immunodeficiency syndrome [AIDS], Lyme disease, heavy metal intoxication). If a secondary cause is not identified, discontinue statin therapy for 3–6 months. If neurologic manifestations improve over this period, a presumptive diagnosis of statin-induced peripheral neuropathy may be made; however, consider reinitiating therapy with a different statin and dosage. If neurologic manifestations do not improve during period of discontinuance, reinitiate statin therapy, taking into consideration the risks and benefits of such therapy.

If manifestations of impaired cognition occur, NLA recommends evaluating and managing patient in similar manner as those experiencing peripheral neuropathy. First, evaluate to rule out secondary causes. If a secondary cause is not identified, discontinue statin therapy for 1–3 months. If no improvement, reinitiate statin therapy, taking into consideration the risks and benefits of such therapy.

Ocular Effects

Cataracts¹ and optic nerve degeneration observed in animals.¹

Risk of Cancer

Fixed combination of simvastatin and ezetimibe (Vytorin) reported in one trial (Simvastatin and Ezetimibe in Aortic Stenosis [SEAS] study) to be possibly associated with increased risk of cancer. Preliminary results of this study in approximately 1900 patients revealed a higher incidence of cancer and fatal cancer in patients receiving the fixed-combination preparation (11.1 and 4.1%, respectively) compared with those receiving placebo (7.5 and 2.5%, respectively). However, interim data from 2 ongoing randomized trials evaluating >20,000 patients with chronic kidney disease or acute coronary syndrome showed no increased risk of cancer following use of the fixed-combination preparation. FDA will review final study report of the SEAS trial to assess additional safety data and provide insight into the risk of cancer.

Use of Fixed Combination

When used in fixed combination with ezetimibe, consider the cautions, precautions, and contraindications associated with ezetimibe.⁸⁸

Specific Populations

Pregnancy

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

Lactation

Not known whether simvastatin is distributed into milk;¹ however, other statins are distributed into milk. Use is contraindicated; discontinue nursing or the drug.¹

Pediatric Use

Safety and efficacy not established in children <10 years of age or in premenarchal girls.¹ Advise adolescent girls to use effective and appropriate contraceptive methods during therapy to reduce the likelihood of unintended pregnancy.¹

Safety and efficacy of fixed-combination preparation (Vytorin) not established in pediatric patients.⁸⁸

Geriatric Use

No substantial differences in safety or efficacy relative to younger adults.¹ Caution in patients (particularly women) of advanced age (≥65 years of age) and in those with small body frame and frailty.¹

No substantial differences in safety or efficacy of fixed-combination preparation with ezetimibe in geriatric patients relative to younger patients; however, increased sensitivity cannot be ruled out.⁸⁸

Hepatic Impairment

Use with caution in patients who consume substantial amounts of alcohol and/or have a history of liver disease.¹

Contraindicated in patients with active liver disease or unexplained, persistent increases in liver function test results.¹

Common Adverse Effects

Upper respiratory tract infections, headache, abdominal pain, constipation, nausea.¹

Interactions for Simvastatin

Simvastatin is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity.¹

Specific Drugs and Foods

Drug or Food	Interaction	Comments
Amiodarone	Increased risk of myopathy and/or rhabdomyolysis, particularly when used with higher dosages of simvastatin1 90 91 92 93	If used concomitantly, simvastatin dosage should not exceed 20 mg daily;1 90 if a simvastatin dosage >20 mg daily is required to achieve target LDL-cholesterol goal, consider use of another statin90
Anticoagulants, oral (e.g., warfarin)	Possible increased PT.1 Bleeding observed with other statins1	Closely monitor PT until stabilized if simvastatin is initiated or dosage is adjusted in patients receiving a coumarin anticoagulant.1 Thereafter, monitor PT at intervals usually recommended for patients receiving coumarin anticoagulants1
Antileukotrienes (e.g., zileuton)	Possible inhibition of CYP3A4	Concomitant use generally should be avoided or undertaken with caution
Azole antifungals (i.e., itraconazole, ketoconazole)	Inhibition of CYP3A4-dependent metabolism of simvastatin, resulting in decreased elimination of simvastatin and increased risk of myopathy and/or rhabdomyolysis1	Concomitant use generally should be avoided.1 If concomitant use is unavoidable, suspend simvastatin therapy during the course of treatment with antifungal.1 Avoid concomitant use of simvastatin with other CYP3A4 inhibitors unless benefits of combined therapy outweigh risks1
Cyclosporine	Inhibition of CYP3A4-dependent metabolism of simvastatin, resulting in decreased elimination of simvastatin and increased risk of myopathy and/or rhabdomyolysis, particularly when used with higher dosages of simvastatin1 88	Weigh benefits against risks of concomitant therapy.1 If used concomitantly, initiate simvastatin at 5 mg daily; simvastatin dosage should not exceed 10 mg daily1
Danazol	Increased risk of myopathy and/or rhabdomyolysis, particularly when used with higher dosages of simvastatin1 88	Weigh benefits against risks of concomitant therapy.1 If used concomitantly, initiate simvastatin at 5 mg daily; simvastatin dosage should not exceed 10 mg daily1
Digoxin	Possible increased plasma digoxin concentrations1	Monitor patients receiving digoxin when simvastatin is initiated1
Diltiazem	Possible increased plasma simvastatin concentrations;1 101 increased risk of myopathy and/or rhabdomyolysis when used with higher dosages of simvastatin1 101	If used concomitantly, simvastatin dosage should not exceed 40 mg daily unless benefit of higher dosage outweighs risk of myopathy1 101
Fibric acid derivatives	Increased risk of myopathy and/or rhabdomyolysis1 Fenofibrate: Pharmacokinetic interaction unlikely1 88 Gemfibrozil: Increased peak plasma concentration and AUC of simvastatin acid1 88	Use concomitantly with caution.1 Concomitant use with gemfibrozil generally should be avoided unless benefits of combined therapy outweigh risks; if used concomitantly, simvastatin dosage should not exceed 10 mg daily1
Fluvoxamine	Possible inhibition of CYP3A4	Concomitant use generally should be avoided or undertaken with caution
Glyburide	Possible increased bioavailability of glyburide
Grapefruit juice	Inhibition of CYP3A4-dependent metabolism of simvastatin, resulting in decreased elimination of simvastatin and increased risk of myopathy and/or rhabdomyolysis1	Concomitant use should be discouraged, or simvastatin dosage reduced accordingly;14 consumption of large quantities (>1 quart daily) of grapefruit juice should be avoided1
HIV protease inhibitors	Inhibition of CYP3A4-dependent metabolism of simvastatin, resulting in decreased elimination of simvastatin and increased risk of myopathy and/or rhabdomyolysis1	Concomitant use generally should be avoided1
Macrolide anti-infectives (i.e., clarithromycin, erythromycin)	Inhibition of CYP3A4-dependent metabolism of simvastatin, resulting in decreased elimination of simvastatin and increased risk of myopathy and/or rhabdomyolysis1	Concomitant use generally should be avoided.1 If concomitant use is unavoidable, suspend simvastatin therapy during the course of treatment with the anti-infective.1 Avoid concomitant use of simvastatin with other CYP3A4 inhibitors unless benefits of combined therapy outweigh risks1
Metronidazole	Possible inhibition of CYP3A4	Concomitant use generally should be avoided or undertaken with caution
Nefazodone	Inhibition of CYP3A4-dependent metabolism of simvastatin, resulting in decreased elimination of simvastatin and increased risk of myopathy and/or rhabdomyolysis1	Concomitant use generally should be avoided1
Niacin	Increased risk of myopathy and/or rhabdomyolysis1 Increased risk of myopathy observed in Chinese versus non-Chinese patients receiving simvastatin 40 mg daily with antilipemic dosages (≥1 g daily) of niacin1 95 101	Concomitant use with antilipemic dosages (≥1 g daily) of niacin generally should be employed with caution; weigh benefits against risks of concomitant therapy1 Patients of Chinese descent should avoid concomitant use of simvastatin 80 mg daily with antilipemic dosages of niacin1 101
Telithromycin	Inhibition of CYP3A4-dependent metabolism of simvastatin, resulting in decreased elimination of simvastatin and increased risk of myopathy and/or rhabdomyolysis1 88	Concomitant use generally should be avoided.1 If concomitant use is unavoidable, suspend simvastatin therapy during the course of treatment with the anti-infective.1 Avoid concomitant use of simvastatin with other CYP3A4 inhibitors unless benefits of combined therapy outweigh risks1
Troleandomycin	Possible inhibition of CYP3A4	Concomitant use generally should be avoided or undertaken with caution
Verapamil	Increased plasma simvastatin concentrations. Increased risk of myopathy and/or rhabdomyolysis, particularly when used with higher dosages of simvastatin1	Concomitant use generally should be avoided; if used concomitantly, simvastatin dosage should not exceed 20 mg daily1

Simvastatin Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following oral administration; undergoes extensive first-pass metabolism in the liver.¹ Absolute bioavailability is <5%.^{1 88} Peak plasma concentrations are attained at 4 hours.¹

Onset

Maximal to near-maximal therapeutic response occurs within 4–6 weeks.¹

Simvastatin-ezetimibe fixed-combination preparation (Vytorin) is bioequivalent to corresponding dosages of the individual components.⁸⁸

Distribution

Extent

Distributed mainly to the liver.¹ Crosses the blood-brain barrier.¹

Plasma Protein Binding

About 95% bound to plasma proteins.¹

Elimination

Metabolism

Metabolized by CYP3A4 to active metabolites.¹

Elimination Route

Excreted in urine (13%) and feces (60%).¹

Half-life

0.5–3 hours.

Special Populations

Patients with moderate to severe renal insufficiency may have decreased clearance of simvastatin and its metabolites.

Stability

Storage

Oral

Tablets

Simvastatin: 5–30°C.¹

Fixed-combination of simvastatin and ezetimibe (Vytorin): Well-closed containers at 20–25°C.⁸⁸

ActionsActions

• 
  

  Prodrug requiring hydrolysis in vivo for activity.¹

  
  


• 
  

  Inhibits HMG-CoA reductase, causing subsequent reduction in hepatic cholesterol synthesis.¹ Reduces serum concentrations of total cholesterol, LDL-cholesterol, VLDL-cholesterol, apo B, and triglycerides.¹

  
  


• 
  

  Statins may slow progression and/or induce regression of atherosclerosis in coronary and/or carotid arteries, modulate BP in hypercholesterolemic patients with hypertension, and possess anti-inflammatory activity.

  
  

Advice to Patients

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

• 
  

  Importance of informing patients about risks, especially myopathy and/or rhabdomyolysis, associated with statins alone or combined with other drugs.^{1 90 91 92 93} Importance of patients promptly reporting unexplained muscle pain, tenderness, or weakness;^{1 90} brown urine; flu-like symptoms; and malaise.

  
  


• 
  

  Importance of adhering to nondrug therapies and measures (i.e., therapeutic lifestyle changes, including dietary management, weight control, physical activity, and management of potentially contributory disease [e.g., diabetes mellitus]).¹

  
  


• 
  

  Importance of obtaining fasting lipoprotein profile and liver function tests periodically.¹

  
  


• 
  

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

  
  


• 
  

  Importance of informing clinician 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.

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

Simvastatin

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	5 mg*	Simvastatin Tablets
			Zocor	Merck
		10 mg*	Simvastatin Tablets
			Zocor	Merck
		20 mg*	Simvastatin Tablets
			Zocor	Merck
		40 mg*	Simvastatin Tablets
			Zocor	Merck
		80 mg*	Simvastatin Tablets
			Zocor	Merck

Simvastatin and Ezetimibe

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	10 mg with Ezetimibe 10 mg	Vytorin	Merck/Schering-Plough
		20 mg with Ezetimibe 10 mg	Vytorin	Merck/Schering-Plough
		40 mg with Ezetimibe 10 mg	Vytorin	Merck/Schering-Plough
		80 mg with Ezetimibe 10 mg	Vytorin	Merck/Schering-Plough

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 07/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Simvastatin 10MG Tablets (ZYDUS PHARMACEUTICALS (USA)): 30/$19.99 or 90/$49.97

Simvastatin 20MG Tablets (DR.REDDY'S LABORATORIES INC.): 30/$27.99 or 90/$73.97

Simvastatin 40MG Tablets (ZYDUS PHARMACEUTICALS (USA)): 30/$27.99 or 90/$75.97

Simvastatin 5MG Tablets (TEVA PHARMACEUTICALS USA): 30/$17.99 or 90/$42.98

Simvastatin 80MG Tablets (ZYDUS PHARMACEUTICALS (USA)): 30/$35.99 or 90/$95.97

Simvastatin 80MG Tablets (DR.REDDY'S LABORATORIES INC.): 30/$35.99 or 90/$95.97

Vytorin 10-10MG Tablets (MERCK/SCHERING-PLOUGH PHARM): 30/$139.55 or 90/$397.14

Vytorin 10-20MG Tablets (MERCK/SCHERING-PLOUGH PHARM): 30/$129.99 or 90/$369.96

Vytorin 10-40MG Tablets (MERCK/SCHERING-PLOUGH PHARM): 30/$135.52 or 90/$398.53

Vytorin 10-80MG Tablets (MERCK/SCHERING-PLOUGH PHARM): 30/$129.99 or 90/$369.96

Zocor 10MG Tablets (MERCK SHARP & DOHME): 30/$93.99 or 90/$269.97

Zocor 20MG Tablets (MERCK SHARP & DOHME): 30/$159.99 or 90/$459.97

Zocor 40MG Tablets (MERCK SHARP & DOHME): 90/$459.98 or 180/$906.63

Zocor 5MG Tablets (MERCK SHARP & DOHME): 30/$71.61 or 90/$192.37

Zocor 5MG Tablets (MERCK SHARP & DOHME): 30/$72.99 or 90/$194.98

Zocor 80MG Tablets (MERCK SHARP & DOHME): 30/$160.99 or 90/$479.97

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions June 09, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Merck & Co., Inc. Zocor (simvastatin) tablets prescribing information. West Point, PA; 2010 May.

2. Anon. Pravastatin, simvastatin, and lovastatin for lowering serum cholesterol concentrations. Med Lett Drugs Ther. 1992; 34:57-8. [PubMed 1593973]

3. Mauro VF, MacDonald JL. Simvastatin: review of its pharmacology and clinical use. DICP. 1991; 25:257-64. [IDIS 279539] [PubMed 2028634]

4. Todd PA, Goa KL. Simvastatin: review of its pharmacological properties and therapeutic potential in hypercholesterolemia. Drugs. 1990; 40:583-607. [PubMed 2083515]

5. Rosen T, Heathcock CH. The synthesis of mevinic acids. Tetrahedron. 1986; 42:4909-51.

6. Brown MS, Goldstein JL. The hyperlipoproteinemias and other disorders of lipid metabolism. In: Harrison’s principles of internal medicine. 11th ed. New York: McGraw-Hill Book Co; 1987:1650-61.

7. Goldstein JL, Brown MS. The low-density lipoprotein pathway and its relation to atherosclerosis. Ann Rev Biochem. 1977; 46:897-930. [PubMed 197883]

8. Brown MS, Goldstein JL. Lipoprotein receptors in the liver: control signals for plasma cholesterol traffic. Clin Invest. 1983; 72:743-7.

9. The Expert Panel. Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Arch Intern Med. 1988; 148:36-69. [IDIS 236890] [PubMed 3422148]

10. National Institutes of Health Office of Medical Applications of Research. Consensus conference: lowering blood cholesterol to prevent heart disease. JAMA. 1985; 25:2080-6.

11. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients withcoronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994; 344:1383-9. [IDIS 338582] [PubMed 7968073]

12. Mauro VF. Clinical pharmacokinetics and practical applications of simvastatin. Drug Dispos. 1993; 24:195-202.

13. Campana C, Iacona I, Regazzi MB et al. Efficacy and pharmacokinetics of simvastatin in heart transplant recipients. Ann Pharmacother. 1995; 29:235-9. [IDIS 344884] [PubMed 7606066]

14. Lilja JJ, Kivisto KT, Neuvonen PJ. Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors. Clin Pharmacol Ther. 1998; 64:477-83. [IDIS 416022] [PubMed 9834039]

15. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA. 1993; 269:3015-23. [IDIS 315201] [PubMed 8501844]

16. England DDF, Viles A, Labib S. Liver side effects associated with simvastatin therapy. Med J Aust. 1991; 155:61. [IDIS 288685] [PubMed 2067448]

17. Manson JM, Freyssinges C, Ducrocq MB et al. Postmarketing surveillance of lovastatin and simvastatin exposure during pregnancy. Reproductive Toxicology. 1996; 10:439-46. [PubMed 8946557]

18. Merck. Zocor formulary information. West Point, PA; 1999 Sep.

19. Stein EA, Davidson MH, Dobs AS et al. Efficacy and safety of simvastatin 80 mg/day in hypercholesterolemic patients. Am J Cardiol. 1998; 82:311-6. [IDIS 412090] [PubMed 9708659]

20. Keech A, Collins R, MacMahon S et al. Three-year follow-up of the oxford cholesterol study: assessment of the efficacy and safety of simvastatin in preparation for a large mortality study. Eur Heart J. 1994; 15:255-69. [PubMed 8005129]

21. Davidson MH, Stein EA, Dujovne CA et al. The efficacy and six-week tolerability of simvastatin 80 and 160 mg/day. Am J Cardiol. 1997; 79:38-42. [IDIS 380398] [PubMed 9024733]

22. Chan P, Huang TY, Tomlinson B et al. Short-term safety and efficacy of low-dose simvastatin in elderly patients with hypertensive hypercholesterolemia and fasting hyperinsulinemia. J Clin Pharmacol. 1997; 37:496-501. [IDIS 389069] [PubMed 9208356]

23. Ito T, Matsumoto M, Hougaku H et al. Effects of low-dose simvastatin therapy on serum lipid levels in patients with moderate hypercholesterolemia: a 12-month study. Clin Ther. 19:487-97. (IDIS 387685)

24. Simons LA. Simvastatin in severe primary hypercholesterolemia: ef