trandolapril and verapamil

Generic Name: trandolapril and verapamil (tran DOL a pril and ver AP a mil)

Brand Names: Tarka

What is trandolapril and verapamil?

Trandolapril is an ACE inhibitor. ACE stands for angiotensin converting enzyme.

Verapamil is a calcium channel blocker. It works by relaxing the muscles of your heart and blood vessels.

The combination of trandolapril and verapamil is used to treat high blood pressure (hypertension).

Trandolapril and verapamil may also be used for purposes not listed in this medication guide.

What is the most important information I should know about trandolapril and verapamil?

Do not use trandolapril and verapamil if you are pregnant. It could harm the unborn baby. Stop using this medication and tell your doctor right away if you become pregnant. You should not use this medicine if you have certain serious heart problems, or if you are allergic to trandolapril (Mavik) or similar medicines such as benazepril (Lotensin), captopril (Capoten), fosinopril (Monopril), enalapril (Vasotec), lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), or ramipril (Altace).

There are many other drugs that can interact with trandolapril and verapamil. Tell your doctor about all medications you use.

Keep using this medicine as directed, even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Tell your doctor if you have a prolonged illness that causes diarrhea or vomiting.

What should I discuss with my healthcare provider before taking trandolapril and verapamil?

You should not use this medicine if you are allergic to trandolapril (Mavik) or verapamil (Calan, Covera, Isoptin, Verelan), or if you have:

• 
  

  certain serious heart conditions, especially "sick sinus syndrome" or "AV block" (unless you have a pacemaker);

  
  


• 
  

  a heart rhythm disorder;

  
  


• 
  

  low blood pressure; or

  
  


• 
  

  if you are allergic to any other ACE inhibitor, such as benazepril (Lotensin), captopril (Capoten), fosinopril (Monopril), enalapril (Vasotec), lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), or ramipril (Altace).

  
  

To make sure you can safely take trandolapril and verapamil, tell your doctor if you have any of these other conditions:

• 
  

  kidney disease (or if you are on dialysis);

  
  


• 
  

  liver disease;

  
  


• 
  

  congestive heart failure;

  
  


• 
  

  diabetes;

  
  


• 
  

  a nerve-muscle disease such as muscular dystrophy; or

  
  


• 
  

  a connective tissue disease such as Marfan syndrome, Sjogren's syndrome, lupus, scleroderma, or rheumatoid arthritis.

  
  

FDA pregnancy category D. Do not use trandolapril and verapamil if you are pregnant. Stop using this medication and tell your doctor right away if you become pregnant. Trandolapril and verapamil can cause injury or death to the unborn baby if you take the medicine during your second or third trimester. Use effective birth control while taking trandolapril and verapamil. Trandolapril and verapamil can pass into breast milk and may harm a nursing baby. You should not breast-feed while you are using trandolapril and verapamil.

How should I take trandolapril and verapamil?

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.

Your doctor may occasionally change your dose to make sure you get the best results.

Trandolapril and verapamil works best if you take it with food.

Your blood pressure will need to be checked often. Visit your doctor regularly.

Conditions that may cause very low blood pressure include: vomiting, diarrhea, heavy sweating, heart disease, dialysis, a low salt diet, or taking diuretics (water pills). Follow your doctor's instructions about the type and amount of liquids you should drink while taking trandolapril and verapamil. Tell your doctor if you have a prolonged illness that causes diarrhea or vomiting. If you need surgery, tell the surgeon ahead of time that you are using trandolapril and verapamil.

Keep using this medicine as directed, even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Store at room temperature away from moisture and heat.

See also: Trandolapril and verapamil dosage (in more detail)

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 slow heart rate, weak pulse, muscle weakness, tingly feeling, seizure (convulsions), feeling light-headed, or fainting.

What should I avoid while taking trandolapril and verapamil?

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Do not use salt substitutes or potassium supplements while taking trandolapril and verapamil, unless your doctor has told you to.

Trandolapril and verapamil side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; severe stomach pain; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have any of these serious side effects:

• 
  

  urinating less than usual or not at all;

  
  


• 
  

  swelling, weight gain, feeling short of breath;

  
  


• 
  

  feeling like you might pass out;

  
  


• 
  

  anxiety, sweating, pale skin, severe shortness of breath, wheezing, gasping for breath, cough with foamy mucus;

  
  


• 
  

  chest pain, fast, slow, or uneven heart rate; or

  
  


• 
  

  fever, upper stomach pain, and jaundice (yellowing of the skin or eyes).

  
  

Less serious side effects may include:

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  cough;

  
  


• 
  

  headache;

  
  


• 
  

  runny or stuffy nose, sore throat;

  
  


• 
  

  constipation, diarrhea;

  
  


• 
  

  dizziness;

  
  


• 
  

  back pain;

  
  


• 
  

  joint pain; or

  
  


• 
  

  nausea.

  
  

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.

Trandolapril and verapamil Dosing Information

Usual Adult Dose for Hypertension:

Initial dose: The initial dosage of trandolapril-verapamil recommended for this patient should be based on this patient's requirements for each drug. The usual recommended dosage range for hypertension for trandolapril and verapamil (sustained-release) is 1 to 4 mg (trandolapril) and 120 to 480 mg (verapamil) per day.

What other drugs will affect trandolapril and verapamil?

Many drugs can interact with trandolapril and verapamil. Below is just a partial list. Tell your doctor if you are using:

• 
  

  buspirone (BuSpar);

  
  


• 
  

  colchicine (Colcrys);

  
  


• 
  

  cyclosporine (Neoral, Sandimmune, Gengraf);

  
  


• 
  

  dexamethasone (Cortastat, Dexasone, Solurex, DexPak);

  
  


• 
  

  digoxin (digitalis, Lanoxin);

  
  


• 
  

  gold injections (to treat arthritis);

  
  


• 
  

  lithium (Lithobid, Eskalith);

  
  


• 
  

  phenobarbital (Solfoton) or other barbiturates;

  
  


• 
  

  insulin or oral diabetes medication;

  
  


• 
  

  sirolimus (Rapamune) or tacrolimus (Prograf);

  
  


• 
  

  St. John's wort;

  
  


• 
  

  theophylline (Elixophyllin, Respbid, Theo-Dur, and others);

  
  


• 
  

  an antibiotic such as clarithromycin (Biaxin), erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin, Pediazole), rifampin (Rifadin, Rifater, Rifamate) and others;

  
  


• 
  

  antifungal medication such as itraconazole (Sporanox), ketoconazole (Nizoral), miconazole (Oravig), or voriconazole (Vfend);

  
  


• 
  

  aspirin or other NSAIDs (non-steroidal anti-inflammatory drugs) such as ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn, Naprelan, Treximet), celecoxib (Celebrex), diclofenac (Arthrotec, Cambia, Cataflam, Voltaren, Flector Patch, Pennsaid, Solareze), indomethacin (Indocin), meloxicam (Mobic), and others;

  
  


• 
  

  a beta-blocker such as atenolol (Tenormin), carvedilol (Coreg), metoprolol (Lopressor, Toprol), propranolol (Inderal, InnoPran), and others;

  
  


• 
  

  a diuretic (water pill);

  
  


• 
  

  drugs to treat high blood pressure or a prostate disorder, such as alfuzosin (Uroxatral), doxazosin (Cardura), prazosin (Minipress), terazosin (Hytrin), tamsulosin (Flomax);

  
  


• 
  

  cholesterol-lowering drugs such as atorvastatin (Lipitor, Caduet), lovastatin (Mevacor, Altoprev, Advicor), or simvastatin (Zocor, Simcor, Vytorin, Juvisync);

  
  


• 
  

  heart rhythm or blood pressure medication such as disopyramide (Norpace), flecainide (Tambocor), nicardipine (Cardene) or quinidine (Quin-G);

  
  


• 
  

  HIV or AIDS medication; or

  
  


• 
  

  seizure medication such as carbamazepine (Carbatrol, Equetro, Tegretol), phenytoin (Dilantin), and others.

  
  

This list is not complete and there are many other drugs that can interact with trandolapril and verapamil. 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. Keep a list of all your medicines and show it to any healthcare provider who treats you.

More trandolapril and verapamil resources

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

Compare trandolapril and verapamil with other medications

• High Blood Pressure

Where can I get more information?

• Your pharmacist can provide more information about trandolapril and verapamil.

See also: trandolapril and verapamil side effects (in more detail)

Increlex

Generic Name: Mecasermin
Class: Somatotropin Agonists
Chemical Name: Insulin-like growth factor I (human)
Molecular Formula: C₃₃₁H₅₁₂N₉₄O₁₀₁S₇
CAS Number: 68562-41-4

Introduction

Somatotropin agonist (a somatomedin); biosynthetic (recombinant DNA origin) form of human insulin-like growth factor I (IGF-1; IGF-I).^{1 8 21}

Uses for Increlex

Insulin-Like Growth Factor I Deficiency

Long-term replacement therapy for treatment of growth failure in children with severe primary insulin-like growth factor I (IGF-I) deficiency (primary IGFD) or growth hormone (GH) gene deletion.^{1 3 13 25}

Designated an orphan drug by FDA for the treatment of GH insensitivity syndrome^{4 11} (i.e., various genetic and acquired conditions with action of GH absent or attenuated).³

Mecasermin rinfabate (Iplex) previously was approved for treatment of growth failure in children with IGF-I deficiency or GH deletion,²² but no longer is commercially available after litigation regarding patent infringement.^{23 24 28} (See Amyotrophic Lateral Sclerosis under Uses.)

Patients with severe primary IGFD have extremely short stature (defined as height standard deviation score not exceeding -3), low serum concentrations of IGF-I (defined as standard deviation score not exceeding -3), and normal or elevated GH secretion.^{1 3 7 25} Primary IGFD may be associated with abnormalities of the GH receptor, post-GH-receptor signaling pathway, or the IGF-I gene resulting in GH insensitivity;^{1 2 25} exogenously administered GH not expected to elicit an adequate response in these patients.^{1 3 25}

Patients with GH gene deletion are likely to develop GH-neutralizing antibodies following exposure to exogenous GH preparations (secondary GH insensitivity syndrome, isolated GH deficiency type IA).^{1 3 13 21}

Not intended for use in children with secondary forms of IGF-I deficiency (e.g., GH deficiency [not including those with GH gene deletion], malnutrition, hypothyroidism, corticosteroid-induced growth failure).^{1 21 25} Correct thyroid and nutritional deficiencies prior to initiation of mecasermin therapy.¹ Not a substitute for GH therapy.¹

Safety and efficacy not established in adults.¹

Amyotrophic Lateral Sclerosis

Mecasermin rinfabate (Iplex), a combination of IGF-I and IGF binding protein-3, has been used in the management of amyotrophic lateral sclerosis† in a limited number of patients.^{26 27 29}

Currently available under a limited-access investigational new drug (IND) protocol.²⁸

Limited evidence with the drug suggests a slower rate of progression of amyotrophic lateral sclerosis, but such findings remain to be confirmed.^{26 27 29}

Increlex Dosage and Administration

General

• 
  

  Administer under supervision of clinicians experienced in diagnosis and management of growth disorders.¹

  
  


• 
  

  Consider monitoring preprandial blood glucose concentrations at treatment initiation and until a well-tolerated dosage is established.^{1 25} If hypoglycemia occurs with recommended dosages despite adequate food intake, reduce dosage.^{1 25} If frequent or severe symptoms of hypoglycemia occur, continue monitoring preprandial blood glucose concentrations.¹ (See Hypoglycemia under Cautions.)

  
  

Administration

Sub-Q Administration

Administer by sub-Q injection into abdomen, buttock, thigh, or upper arm.^{1 25} Rotate injection sites with each injection.^{1 5} Use low-volume syringe to ensure accuracy of dosing.^{1 5}

Do not administer IV or IM.^{1 5}

Give shortly (≤20 minutes) before or after meal or snack to reduce risk of hypoglycemia.^{1 5 25} If child is unable to eat shortly before or after drug administration, withhold dose.^{1 5 13} Do not increase dosage of mecasermin to replace one or more missed doses.^{1 5} Take particular care with young children, whose oral intake may not be consistent.¹

Dosage

Pediatric Patients

Insulin-Like Growth Factor I Deficiency

Sub-Q

Children ≥2 years of age: Initially, 0.04–0.08 mg/kg twice daily.^{1 25} If well tolerated for ≥1 week (e.g., no hypoglycemic episodes), increase dosage by 0.04 mg/kg per dose to a maximum dosage of 0.12 mg/kg twice daily.^{1 25} Continue therapy until closure of epiphyses.^{11 21}

Prescribing Limits

Pediatric Patients

Insulin-Like Growth Factor I Deficiency

Sub-Q

Children ≥2 years of age: Maximum 0.12 mg/kg twice daily.^{1 25} Dosages of mecasermin >0.12 mg/kg twice daily not evaluated and not recommended for use in children.¹

Special Populations

No special population dosage recommendations at this time.¹

Cautions for Increlex

Contraindications

• 
  

  Children with closed epiphyses.¹

  
  


• 
  

  Known hypersensitivity to mecasermin or any ingredient (e.g., benzyl alcohol) in the formulation.¹ (See Pediatric Use under Cautions.)

  
  


• 
  

  Active or suspected neoplasm; discontinue therapy if evidence of neoplasm develops.¹

  
  

Warnings/Precautions

Warnings

Benzyl Alcohol in Neonates

Mecasermin contains benzyl alcohol as a preservative, which has been associated with toxicity (fatalities) in neonates.^{1 12 17 18 19 20} (See Pediatric Use under Cautions.)

Sensitivity Reactions

Local or systemic allergic reactions reported.¹ If allergic reaction occurs, discontinue mecasermin therapy.¹ (See Advice to Patients.)

General Precautions

Hypoglycemia

Hypoglycemia (generally mild to moderate) reported, particularly during the first month of treatment; young children and those with a history of hypoglycemia are at higher risk.^{1 11 13 25} (See Actions.)

Increased risk of hypoglycemia with insufficient caloric intake or concurrent drug use (e.g., antidiabetic agents).^{1 5} (See Specific Drugs under Interactions.)

Consider monitoring preprandial blood glucose concentrations at treatment initiation and until a well-tolerated dosage is established.¹ (See General under Dosage and Administration and also see Advice to Patients.)

Use a rapidly absorbed carbohydrate (e.g., orange juice, candy, glucose gel, milk) for treatment of mild to moderate hypoglycemia.⁵ Severe hypoglycemia (associated with altered states of consciousness) may require use of IV glucagon.⁵

Lymphoid Tissue Hypertrophy

Lymphoid tissue hypertrophy may occur.^{1 3 13 25} Tonsillar hypertrophy reported more frequently in the first 1–2 years of therapy.^{1 25}

Examine patients periodically to rule out potential complications (e.g., snoring, sleep apnea, chronic middle ear effusions, dyspnea, dysphagia) and administer appropriate treatment, if necessary.^{1 5} (See Advice to Patients.)

Intracranial Hypertension

Intracranial hypertension with papilledema, visual changes, headache, nausea and/or vomiting reported.^{1 2 13 15 25} Such effects may resolve spontaneously during continued therapy or after interruption of therapy.^{1 5 13 25} Upon resolution, therapy may be resumed at the lowest previously tolerated dosage; the maximum recommended dosage (0.12 mg/kg twice daily) may eventually be reinitiated in some of these patients without recurrence of intracranial hypertension.²¹

Funduscopic examination recommended at treatment initiation and periodically thereafter (e.g., at each follow-up visit, if headache is present).^{1 21} (See Advice to Patients.)

Slipped Capital Femoral Epiphysis

Slipped capital femoral epiphysis can occur in patients who experience rapid growth.¹ Monitor patient for hip or knee pain or limping and other signs and symptoms generally known to be associated with GH treatment.^{1 5} (See Advice to Patients.)

Progression of Scoliosis

Progression of scoliosis can occur in patients who experience rapid growth.¹ Monitor patient for increased curvature of the spine and other signs and symptoms generally known to be associated with GH treatment.^{1 5} (See Advice to Patients.)

Effects on Facial Growth

Facial effects (e.g., thickening and overgrowth of soft tissues) reported.^{1 3 11 25} Monitor patients for signs and symptoms of this condition.¹

Specific Populations

Pregnancy

Category C.¹

Not indicated for use in adults, including pregnant women.¹

Lactation

Not known whether mecasermin is distributed into milk.¹ Use caution.¹

Not indicated for use in adults, including nursing women.¹

Pediatric Use

Safety and efficacy not established in children <2 years of age.¹

Large amounts of benzyl alcohol (i.e., 100–400 mg/kg daily) associated with toxicity in neonates;^{12 17 18 19 20} each mL of mecasermin contains 9 mg of benzyl alcohol.¹ Not indicated for use in neonates.¹

Geriatric Use

Safety and efficacy not established in patients ≥65 years of age.¹

Not indicated for use in adults, including geriatric patients.¹

Hepatic Impairment

Not studied in patients with hepatic impairment.^{1 11}

Renal Impairment

Not studied in patients with renal impairment.^{1 11}

Common Adverse Effects

Hypoglycemia,^{1 11 13 16 25} injection site lipohypertrophy,^{1 2 3 11 13 25} headache,^{1 11} hypoacusis,^{1 11 13 25} vomiting,^{1 11} otitis media,^{1 11} tonsillar/adenoidal hypertrophy,^{1 11 13 16 25} thymus hypertrophy,^{1 11 13 25} fluid in middle ear,^{1 11 13} arthralgia,^{1 11 25} extremity pain,^{1 11} cardiac murmur,^{1 11} dizziness,^{1 11} ear pain,^{1 11} injection site bruising,^{1 11} abnormal tympanometry,^{1 11} seizures.^{1 11}

Interactions for Increlex

Specific Drugs

Drug	Interaction	Comments
Antidiabetic agents	Potential risk of hypoglycemia5 21	Dosage adjustments of antidiabetic agents may be necessary5

Increlex Pharmacokinetics

Absorption

Bioavailability

Following sub-Q administration in healthy individuals, bioavailability is approximately 100%.^{1 16 25} Bioavailability in individuals with IGF-I deficiency not determined.^{1 25}

In individuals with severe IGF-I deficiency, serum concentrations of IGF-I were very low prior to mecasermin administration.¹¹ Following administration of a single dose (0.12 mg/kg) in these individuals, average peak plasma concentrations attained at 2 hours were below normal or in the low-normal range.^{1 11 13 16 25}

Distribution

Extent

Tissue availability of free IGF-I determined by presence of 6 IGF binding proteins (IGFBPs) in the blood.^{1 8 11} IGFBPs, particularly IGFBP-3, limit the extent of distribution.¹¹

Not known whether mecasermin is distributed into milk.¹

Plasma Protein Binding

>99% of circulating IGF-I bound to IGFBPs,^{1 8} with >80% bound as a complex with IGFBP-3 and an acid labile subunit.^{1 8 25} Plasma concentrations of IGFBP-3 and acid labile subunit are reduced in patients with severe primary IGFD compared with healthy individuals, resulting in greater drug clearance.^{1 3 14 15} (See Half-life under Pharmacokinetics.)

Elimination

Metabolism

Mecasermin and endogenous IGF-I are metabolized by lysosomal enzymes principally in the liver and kidneys to amino acids.^{1 11 16 21 25}

Elimination Route

Excreted principally in urine.^{16 21} Presumably less than 0.1% is excreted in urine as unchanged drug based on studies with endogenous IGF-I.²¹

Half-life

Terminal half-life averages 5.8 hours in children with severe primary IGFD^{1 11 16 25} and 19.2 hours in healthy individuals.^{1 11 16}

Clearance of free IGF-I occurs at a faster rate than IGF-I bound to IGFBPs; therefore, patients with severe primary IGFD have increased clearance and shorter half-life of IGF-I compared with healthy individuals.^{1 3 11 14} (See Plasma Protein Binding under Pharmacokinetics.)

Stability

Storage

Parenteral

Solution for Sub-Q Injection

2–8°C; protect from light and freezing.^{1 5} If freezing occurs, do not use.⁵

Opened vials stable at 2–8°C for 30 days.^{1 5} Discard any remaining solution if not used within 30 days.^{1 5}

ActionsActions

• 
  

  Mecasermin is a biosynthetic (recombinant DNA origin) form of human IGF-I and the principal mediator of somatotropic effects of human GH (somatotropin).¹

  
  


• 
  

  GH binds to GH receptors in the liver and other tissues and stimulates the synthesis/secretion of IGF-I.^{1 8 9 13 25} IGF-I activates IGF-I receptors, leading to intracellular signals that stimulate growth.^{1 9 25}

  
  


• 
  

  Many actions of GH mediated through IGF-I; however, the precise roles of GH and IGF-I not fully elucidated.^{8 9 13}

  
  


• 
  

  Stimulates mitogenesis in many tissues.^{1 9}

  
  


• 
  

  Bypasses blockade of GH action and stimulates growth in the presence of GH receptor mutations, abnormalities of the post-GH-receptor signaling pathway, or defects in the IGF-I or GH gene.^{3 7 9 13}

  
  


• 
  

  Promotes linear growth by stimulating proliferation of chondrocytes in epiphyseal cartilage, proliferation of osteoblasts, and formation of soft connective tissue (as evidenced by increased production of procollagen).^{1 2 7 8}

  
  


• 
  

  Promotes growth of various organs, including spleen, kidneys, brain, and lymphoid tissues.^{1 2 3 11 13 25} (See Lymphoid Tissue Hypertrophy under Cautions.)

  
  


• 
  

  Stimulates uptake of fatty acids and amino acids to support growing tissues.^{1 25}

  
  


• 
  

  Structurally similar to insulin; binds with low affinity to insulin receptors and suppresses hepatic glucose production and stimulates peripheral glucose utilization.^{1 8} These effects may result in hypoglycemia particularly during the first month of treatment.^{1 2} Exogenous IGF-I inhibits insulin secretion resulting in reduced likelihood of hypoglycemia during long-term administration.^{1 2} (See Hypoglycemia under Cautions.)

  
  

Advice to Patients

• 
  

  Provide copy of manufacturer’s patient information to the patient and/or patient’s parent or guardian and advise of the importance of reading this information each time a new or refill prescription is dispensed.⁵

  
  


• 
  

  Importance of advising patients and/or patient’s parent or guardian about safe administration of the drug and proper disposal of used needles and syringes.^{1 5}

  
  


• 
  

  Importance of administering the drug ≤20 minutes before or after a meal or snack.^{1 5} Advise patient and/or patient’s parent or guardian not to administer the drug if the meal or snack is omitted prior to administration and not to make up the missed dose.^{1 5}

  
  


• 
  

  Importance of proper glucose monitoring and how to recognize signs and symptoms of hypoglycemia.^{1 5} Advise patient and/or patient’s parent or guardian to always keep a source of carbohydrates (e.g., orange juice, candy) available in case hypoglycemia occurs.^{1 5} For severe cases, advise patient and/or patient’s parent or guardian on the proper use of glucagon injection.^{1 5}

  
  


• 
  

  Importance of avoiding high-risk activities (e.g., driving) within 2–3 hours following drug administration, particularly after therapy initiation, until a well-tolerated dosage established.^{1 5}

  
  


• 
  

  Importance of advising patients and/or patient’s parent or guardian of possible allergic reactions.^{1 5} Importance of discontinuing therapy and contacting a clinician promptly if allergic reactions (e.g., rash, hives, breathing problems, shock) occur.^{1 5}

  
  


• 
  

  Advise patient and/or patient’s parent or guardian that the drug should not be used if the child has finished growing (i.e., bone growth plates are closed), has cancer, or has causes of growth failure other than primary IGF-I deficiency.^{1 5}

  
  


• 
  

  Importance of informing clinicians if signs and symptoms of enlarged tonsils (e.g., snoring, breathing or swallowing problems, sleep disorders, hearing disorders, fluid in middle ear) occur.^{1 5}

  
  


• 
  

  Importance of informing clinicians if signs and symptoms of increased pressure in the brain (e.g., headache, nausea, vomiting, vision disorders) occur.^{1 5} Advise patient that funduscopic examination is recommended at treatment initiation and periodically thereafter.¹

  
  


• 
  

  Importance of informing clinicians immediately if the patient develops a limp or hip or knee pain, since these may be signs of a slipped capital femoral epiphysis (a condition that occurs when the top of the femur slips apart from the ball of the hip joint).⁵

  
  


• 
  

  Risk of worsening scoliosis caused by rapid growth.^{1 5} Importance of clinicians evaluating patients with scoliosis for increased curvature of the spine during therapy.^{1 5}

  
  


• 
  

  Importance of patients informing clinicians if they are or plan to become pregnant or plan to breast-feed.⁵

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (e.g., insulin, other antidiabetic agents), vitamins, and herbal supplements, as well as any concomitant illnesses (e.g., diabetes mellitus, kidney or liver disease, curved spine).^{1 5}

  
  


• 
  

  Importance of informing patients and/or patient’s parent or guardian 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.

Mecasermin (Recombinant DNA Origin)

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection, for subcutaneous use	10 mg/mL (40 mg)	Increlex	Tercica

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 August 2009. 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. Tercica. Increlex (mecasermin) injection prescribing information. Brisbane, CA; 2007 Aug.

2. Laron Z. The essential role of IGF-I: lessons from the long-term study and treatment of children and adults with Laron syndrome. J Clin Endocrinol Metab. 1999; 84:4397-404. [PubMed 10599694]

3. Backeljauw PF, Underwood LE, GHIS Collaborative Group. Therapy for 6.5–7.5 years with recombinant insulin-like growth factor I in children with growth hormone insensitivity syndrome: a clinical research center study. J Clin Endocrinol Metab. 2001; 86:1504-10. [PubMed 11297575]

4. Food and Drug Administration. List of all orphan products designated and approved. From FDA web site . 2006 Jan 24.

5. Tercica. Increlex (mecasermin) injection patient information. Brisbane, CA; 2007 Oct.

7. Klinger B, Jensen LT, Sibergeld A et al. Insulin-like growth factor-I raises serum procollagen levels in children and adults with Laron syndrome. Clin Endocrinol. 1996; 45:423-9.

8. Laron Z. Insulin-like growth factor 1 (IGF-1): a growth hormone. J Clin Pathol: Mol Pathol. 2001; 54:311-6.

9. Reiter ED, Rosenfeld RG. Normal and aberrant growth. In: Larsen PR, Kronenberg HM, Melmed S et al., eds. Williams textbook of endocrinology. 10th ed. Philadelphia, PA: Saunders; 2003:1003-114.

11. Meyer RJ. Mecasermin injection, Increlex: medical review, FDA approval package. NDA number: 21-839. Rockville, MD: US Food and Drug Administration; 2005 Aug 30.

12. American Academy of Pediatrics Committee on Fetus and Newborn and Committee on Drugs. Benzyl alcohol: toxic agent in neonatal units. Pediatrics. 1983; 72:356-8. [IDIS 175725] [PubMed 6889041]

13. Chernausek SD, Backeljauw PF, Frane J et al. Long-term treatment with recombinant insulin-like growth factor (IGF)-I in children with severe IGF-I deficiency due to growth hormone insensitivity. J Clin Endocrinol Metab. 2007; 92:902-10. [PubMed 17192294]

14. Rosenbloom AL, Guevara-Aguirre J, Rosenfeld RG et al. Growth hormone receptor deficiency in Ecuador. J Clin Endocrinol Metab. 1999; 84:4436-43. [PubMed 10599699]

15. Guevara-Aguirre J, Vasconez O, Martinez V et al. A randomized, double-blind, placebo-controlled trial on safety and efficacy of recombinant human insulin-like growth factor-I in children with growth hormone receptor deficiency. J Clin Endocrinol Metab. 1995; 80:1393-8.

16. Chung S, Ahn HY. Mecasermin injection, Increlex: clinical pharmacology and biopharmaceutics review(s), FDA approval package. NDA number: 21-839. Rockville, MD: US Food and Drug Administration; 2005 Aug 30.

17. Centers for Disease Control. Neonatal deaths associated with use of benzyl alcohol. MMWR. 1982; 31:290-1. [IDIS 150868] [PubMed 6810084]

18. Gershanik J, Boecler B, Ensley H et al. The gasping syndrome and benzyl alcohol poisoning. N Engl J Med. 1982; 307:1384-8. [IDIS 160823] [PubMed 7133084]

19. Menon PA, Thach BT, Smith CH et al. Benzyl alcohol toxicity in a neonatal intensive care unit: incidence, symptomatology, and mortality. Am J Perinatol. 1984; 1:288-92. [PubMed 6440575]

20. Anderson CW, Ng KJ, Andresen B et al. Benzyl alcohol poisoning in a premature newborn infant. Am J Obstet Gynecol. 1984; 148:344-6. [IDIS 181207] [PubMed 6695984]

21. Tercica, Brisbane, CA: Personal communication.

22. Insmed. IPLEX (mecasermin rinfabate) prescribing information. Glen Allen, VA; 2005 Dec 8.

23. Insmed. IPLEX press release. Available at . Accessed Mar 4, 2009.

24. Life Sciences Law & Industry. Insmed settles all litigation over Iplex, will stop selling drug for growth treatment. Mar 16, 2007.

25. Keating GM. Mecasermin. Biodrugs. 2008; 22:177-88. [PubMed 18481900]

26. Lai EC, Felice KJ, Festoff BW et al. Effect of recombinant human insulin-like growth factor-I on progression of ALS. A placebo-controlled study. The North America ALS/IGF-I Study Group. Neurology. 1997; 49:1621-30. [PubMed 9409357]

27. Department of Health and Human Services, Food and Drug Administration. FDA summary of controlled clinical data for human IGF-1 in treatment of patients with amyotrophic lateral sclerosis. 2009 Mar 10. Available at: . Accessed 2009 Mar 27.

28. Food and Drug Administration, Center for Drug Evaluation and Research. FDA position on allowing patients with ALS access to Iplex under an IND. 2009 Mar 10. Available at: . Accessed 2009 Mar 27.

29. Mitchell JD, Wokke JH, Borasio GD. Recombinant human insulin-like growth factor I (rhIGF-I) for amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst Rev. 2007; :CD002064. [PubMed 17943766]

More Increlex resources

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

• Increlex Prescribing Information (FDA)


• Increlex Consumer Overview


• Increlex Advanced Consumer (Micromedex) - Includes Dosage Information


• Increlex MedFacts Consumer Leaflet (Wolters Kluwer)


• Mecasermin Professional Patient Advice (Wolters Kluwer)

Compare Increlex with other medications

• Primary IGF-1 Deficiency

Polygam S/D IGIV

Generic Name: immune globulin (intravenous) (IGIV) (im MYOON GLOB yoo lin)

Brand Names: Carimune, Flebogamma, Gammagard (obsolete), Gammagard S/D, Gammaplex, Gammar-P I.V., Gamunex, Octagam, Polygam S/D, Privigen, Sandoglobulin

What is immune globulin intravenous (IVIG)?

Immune globulin intravenous is a sterilized solution made from human plasma. It contains the antibodies to help your body protect itself against infection from various diseases.

Immune globulin is used to treat primary immune deficiency, and to reduce the risk of infection in individuals with poorly functioning immune systems such as those with chronic lymphocytic leukemia (CLL). IGIV is also used to increase platelets (blood clotting cells) in people with idiopathic thrombocytopenic purpura (ITP) and to prevent aneurysm caused by a weakening of the main artery in the heart associated with Kawasaki syndrome.

Immune globulin is also used to treat chronic inflammatory demyelinating polyneuropathy (CIDP), a debilitating nerve disorder that causes muscle weakness and can affect daily activities.

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

What is the most important information I should know about immune globulin?

Immune globulin can harm your kidneys, and this effect is increased when you also use certain other medicines harmful to the kidneys. Before using immune globulin, tell your doctor about all other medications you use. Many other drugs (including some over-the-counter medicines) can be harmful to the kidneys.

Before using immune globulin intravenous, tell your doctor if you have kidney disease, diabetes (especially if you use insulin), a history of stroke or blood clot, heart disease, high blood pressure, a condition called paraproteinemia, or if you are over 65 years old.

To be sure this medicine is helping your condition and is not causing harmful effects, your blood will need to be tested often. Your kidney function may also need to be tested. Visit your doctor regularly.

This medication can cause unusual results with certain blood glucose tests. Tell any doctor who treats you that you are using immune globulin.

Immune globulin is made from human plasma (part of the blood) which may contain viruses and other infectious agents. Donated plasma is tested and treated to reduce the risk of it containing infectious agents, but there is still a small possibility it could transmit disease. Talk with your doctor about the risks and benefits of using this medication.

What should I discuss with my health care provider before using immune globulin?

You should not use this medication if you have ever had an allergic reaction to an immune globulin or if you have immune globulin A (IgA) deficiency with antibody to IgA.

To make sure you can safely use immune globulin, tell your doctor if you have any of these other conditions:

• 
  

  kidney disease;

  
  


• 
  

  diabetes (especially if you use insulin);

  
  


• 
  

  a history of stroke or blood clot;

  
  


• 
  

  heart disease or high blood pressure;

  
  


• 
  

  a condition called paraproteinemia; or

  
  


• 
  

  if you are over 65 years old.

  
  

FDA pregnancy category C. It is not known whether immune globulin will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication. It is not known if immune globulin 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.

Immune globulin is made from human plasma (part of the blood) which may contain viruses and other infectious agents. Donated plasma is tested and treated to reduce the risk of it containing infectious agents, but there is still a small possibility it could transmit disease. Talk with your doctor about the risks and benefits of using this medication.

How is immune globulin intravenous given?

Immune globulin intravenous is injected into a vein through an IV. You may be shown how to use an IV at home. Do not self-inject this medicine if you do not fully understand how to give the injection and properly dispose of used needles, IV tubing, and other items used to inject the medicine.

IVIG should not be injected into a muscle or under the skin.

Do not use the medication if it has changed colors or has particles in it. Call your doctor for a new prescription. Throw away any unused medicine that is left over after injecting your dose.

Use each disposable needle only one time. Throw away used needles in a puncture-proof container (ask your pharmacist where you can get one and how to dispose of it). Keep this container out of the reach of children and pets.

IVIG is usually given every 3 to 4 weeks. Your dosing schedule may be different. Follow your doctor's instructions.

Your doctor may occasionally change your dose to make sure you get the best results.

To be sure this medicine is helping your condition and is not causing harmful effects, your blood will need to be tested often. Your kidney function may also need to be tested. Visit your doctor regularly.

This medication can cause unusual results with certain blood glucose tests. Tell any doctor who treats you that you are using immune globulin.

Some brands of immune globulin should be stored in a refrigerator, while others can be kept at room temperature. Follow the directions on your prescription label or ask your pharmacist if you have questions about how to store the medication. Do not allow the medicine to freeze.

What happens if I miss a dose?

Call your doctor for instructions if you miss a dose of this medication.

What happens if I overdose?

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

What should I avoid while using immune globulin?

Do not receive a "live" vaccine while using IVIG. The vaccine may not work as well during this time, and may not fully protect you from disease. Live vaccines include measles, mumps, rubella (MMR), oral polio, typhoid, chickenpox (varicella), BCG (Bacillus Calmette and Guérin), and nasal flu vaccine.

Immune globulin 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 a serious side effect such as:

• 
  

  urinating less than usual or not at all;

  
  


• 
  

  drowsiness, confusion, mood changes, increased thirst, loss of appetite, nausea and vomiting;

  
  


• 
  

  swelling, weight gain, feeling short of breath;

  
  


• 
  

  wheezing, chest tightness;

  
  


• 
  

  feeling like you might pass out;

  
  


• 
  

  fever with headache, neck stiffness, chills, increased sensitivity to light, purple spots on the skin, and/or seizure (convulsions); or

  
  


• 
  

  pale or yellowed skin, dark colored urine, fever, confusion or weakness.

  
  

Less serious side effects may include:

• 
  

  mild headache;

  
  


• 
  

  dizziness;

  
  


• 
  

  tired feeling;

  
  


• 
  

  back pain, muscle cramps;

  
  


• 
  

  minor chest pain; or

  
  


• 
  

  flushing (warmth, redness, or tingly feeling).

  
  

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 immune globulin?

Immune globulin can harm your kidneys. This effect is increased when you also use other medicines harmful to the kidneys. You may need dose adjustments or special tests if you have recently used:

• 
  

  lithium (Lithobid);

  
  


• 
  

  methotrexate (Rheumatrex, Trexall);

  
  


• 
  

  pain or arthritis medicines such as aspirin (Anacin, Excedrin), acetaminophen (Tylenol), diclofenac (Cataflam, Voltaren), etodolac (Lodine), ibuprofen (Advil, Motrin), indomethacin (Indocin), meloxicam (Mobic), nabumetone (Relafen), naproxen (Aleve, Naprosyn), piroxicam (Feldene), and others;

  
  


• 
  

  medicines used to treat ulcerative colitis, such as mesalamine (Pentasa) or sulfasalazine (Azulfidine);

  
  


• 
  

  medicines used to prevent organ transplant rejection, such as cyclosporine (Gengraf, Neoral, Sandimmune), sirolimus (Rapamune) or tacrolimus (Prograf);

  
  


• 
  

  IV antibiotics such as amphotericin B (Fungizone, AmBisome, Amphotec, Abelcet), amikacin (Amikin), bacitracin (Baci-IM), capreomycin (Capastat), gentamicin (Garamycin), kanamycin (Kantrex), streptomycin, or vancomycin (Vancocin, Vancoled);

  
  


• 
  

  antiviral medicines such as adefovir (Hepsera), cidofovir (Vistide), or foscarnet (Foscavir); or

  
  


• 
  

  cancer medicine such as aldesleukin (Proleukin), carmustine (BiCNU, Gliadel), cisplatin (Platinol), ifosfamide (Ifex), oxaliplatin (Eloxatin), streptozocin (Zanosar), or tretinoin (Vesanoid).

  
  

This list is not complete and other drugs may interact with immune globulin. 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 Polygam S/D resources

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

Compare Polygam S/D with other medications

• Autoimmune Neutropenia
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• Evan's Syndrome
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• Idiopathic Thrombocytopenic Purpura
• Kawasaki Disease
• Polymyositis/Dermatomyositis
• Primary Immunodeficiency Syndrome

Where can I get more information?

• Your pharmacist can provide more information about immune globulin intravenous.

See also: Polygam S/D side effects (in more detail)

Clobetasol Cream

Dosage Form: cream
Clobetasol Propionate

Cream (Emollient) USP, 0.05%

Rx only

FOR TOPICAL DERMATOLOGIC USE ONLY - NOT FOR OPHTHALMIC, ORAL, OR INTRAVAGINAL USE

Clobetasol Cream Description

Clobetasol propionate cream (emollient) contains the active compound clobetasol propionate, a synthetic corticosteroid, for topical dermatologic use. Clobetasol, an analog of prednisolone, has a high degree of glucocorticoid activity and a slight degree of mineralocorticoid activity.

Chemically, clobetasol propionate is (11β,16β) - 21 - chloro - 9 - fluoro - 11 - hydroxy - 16 - methyl - 17 - (1 - oxopropoxy) - pregna - 1,4 - diene - 3,20 - dione and it has the following structural formula:

Clobetasol propionate has the molecular formula C25H32ClFO5 and a molecular weight of 466.98. It is a white to cream-colored crystalline powder insoluble in water.

Clobetasol propionate cream (emollient) contains clobetasol propionate 0.5 mg/g in an emollient base of cetomacrogol 1000, cetostearyl alcohol, citric acid, dimethicone 350, imidurea, isopropyl myristate, propylene glycol, purified water, and sodium citrate.

Clobetasol Cream - Clinical Pharmacology

Like other topical corticosteroids, clobetasol propionate has anti-inflammatory, antipruritic, and vasoconstrictive properties. The mechanism of the anti-inflammatory activity of the topical steroids, in general, is unclear. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2.

Pharmacokinetics

The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle and the integrity of the epidermal barrier. Occlusive dressing with hydrocortisone for up to 24 hours has not been demonstrated to increase penetration; however, occlusion of hydrocortisone for 96 hours markedly enhances penetration. Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin may increase percutaneous absorption.

Studies performed with clobetasol propionate cream (emollient) indicate that it is in the super-high range of potency as compared with other topical corticosteroids.

Indications and Usage for Clobetasol Cream

Clobetasol propionate cream (emollient) is a super-high potency corticosteroid formulation indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. Treatment beyond 2 consecutive weeks is not recommended, and the total dosage should not exceed 50 g/week because of the potential for the drug to suppress the hypothalamic-pituitary-adrenal (HPA) axis. Use in pediatric patients under 12 years of age is not recommended.

In the treatment of moderate to severe plaque-type psoriasis, clobetasol propionate cream (emollient) applied to 5% to 10% of body surface area can be used up to 4 consecutive weeks. The total dosage should not exceed 50 g/week. When dosing for more than 2 weeks, any additional benefits of extending treatment should be weighed against the risk of HPA suppression. Treatment beyond 4 consecutive weeks is not recommended. Patients should be instructed to use clobetasol propionate cream (emollient) for the minimum amount of time necessary to achieve the desired results (see PRECAUTIONS and INDICATIONS AND USAGE). Use in pediatric patients under 16 years of age has not been studied.

Contraindications

Clobetasol propionate cream (emollient) is contraindicated in those patients with a history of hypersensitivity to any of the components of the preparation.

Precautions

General

Clobetasol propionate is a highly potent topical corticosteroid that has been shown to suppress the HPA axis at doses as low as 2 g/day.

Systemic absorption of topical corticosteroids can produce reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal from treatment. Manifestations of Cushing's syndrome, hyperglycemia, and glucosuria can also be produced in some patients by systemic absorption of topical corticosteroids while on therapy.

Patients applying a dose to a large surface area or to areas under occlusion should be evaluated periodically for evidence of HPA axis suppression. This may be done by using the ACTH stimulation, A.M. plasma cortisol, and urinary free cortisol tests. Patients receiving super-potent corticosteroids should not be treated for more than 2 weeks at a time, and only small areas should be treated at any one time due to the increased risk of HPA suppression.

In a controlled clinical trial involving patients with moderate to severe plaque-type psoriasis, clobetasol propionate cream (emollient) applied to 5% to 10% of body surface area resulted in additional benefits in the treatment of patients for 4 consecutive weeks. In this trial, there were no clobetasol-treated patients with clinically significant decreases in morning cortisol levels after 4 weeks of treatment; however, morning cortisol levels may not identify patients with adrenal dysfunction. Therefore, the additional benefits of extending treatment beyond 2 weeks should be weighed against the potential for HPA suppression. Therapy should be discontinued when control has been achieved. Treatment beyond 4 consecutive weeks is not recommended.

If HPA axis suppression is noted, an attempt should be made to withdraw the drug, to reduce the frequency of application, or to substitute a less potent corticosteroid. Recovery of HPA axis function is generally prompt upon discontinuation of topical corticosteroids. Infrequently, signs and symptoms of glucocorticosteroid insufficiency may occur that require supplemental systemic corticosteroids. For information on systemic supplementation, see prescribing information for those products.

Pediatric patients may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios (see PRECAUTIONS: Pediatric Use). The use of clobetasol propionate cream (emollient) for 4 consecutive weeks has not been studied in pediatric patients under 16 years of age.

If irritation develops, clobetasol propionate cream (emollient) should be discontinued and appropriate therapy instituted. Allergic contact dermatitis with corticosteroids is usually diagnosed by observing a failure to heal rather than noting a clinical exacerbation as with most topical products not containing corticosteroids. Such an observation should be corroborated with appropriate diagnostic patch testing.

If concomitant skin infections are present or develop, an appropriate antifungal or antibacterial agent should be used. If a favorable response does not occur promptly, use of clobetasol propionate cream (emollient) should be discontinued until the infection has been adequately controlled.

Clobetasol propionate cream (emollient) should not be used in the treatment of rosacea or perioral dermatitis, and should not be used on the face, groin, or axillae.

Information for Patients

Patients using topical corticosteroids should receive the following information and instructions:

1. This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes.


2. This medication should not be used for any disorder other than that for which it was prescribed.


3. The treated skin area should not be bandaged, otherwise covered, or wrapped so as to be occlusive unless directed by the physician.


4. Patients should report any signs of local adverse reactions to the physician.


5. Patients should inform their physicians that they are using clobetasol propionate cream (emollient) if surgery is contemplated.


6. This medication should not be used on the face, underarms, or groin areas.


7. As with other corticosteroids, therapy should be discontinued when control has been achieved. If no improvement is seen within 2 weeks, contact the physician.

Laboratory Tests

The following tests may be helpful in evaluating patients for HPA axis suppression:

 

ACTH stimulation test

 

A.M. plasma cortisol test

 

Urinary free cortisol test

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal studies have not been performed to evaluate the carcinogenic potential of clobetasol propionate.

Studies in the rat following subcutaneous administration at dosage levels up to 50 mcg/kg per day revealed that the females exhibited an increase in the number of resorbed embryos and a decrease in the number of living fetuses at the highest dose.

Clobetasol propionate was nonmutagenic in three different test systems: the Ames test, the Saccharomyces cerevisiae gene conversion assay, and the E. coli B WP2 fluctuation test.

Pregnancy

Teratogenic Effects

Pregnancy Category C

Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Some corticosteroids have been shown to be teratogenic after dermal application to laboratory animals.

Clobetasol propionate has not been tested for teratogenicity when applied topically; however, it is absorbed percutaneously, and when administered subcutaneously it was a significant teratogen in both the rabbit and mouse. Clobetasol propionate has greater teratogenic potential than steroids that are less potent.

Teratogenicity studies in mice using the subcutaneous route resulted in fetotoxicity at the highest dose tested (1 mg/kg) and teratogenicity at all dose levels tested down to 0.03 mg/kg. These doses are approximately 1.4 and 0.04 times, respectively, the human topical dose of clobetasol propionate cream (emollient). Abnormalities seen included cleft palate and skeletal abnormalities.

In rabbits, clobetasol propionate was teratogenic at doses of 3 and 10 mcg/kg. These doses are approximately 0.02 and 0.05 times, respectively, the human topical dose of clobetasol propionate cream (emollient). Abnormalities seen included cleft palate, cranioschisis, and other skeletal abnormalities.

There are no adequate and well-controlled studies of the teratogenic potential of clobetasol propionate in pregnant women. Clobetasol propionate cream (emollient) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. Because many drugs are excreted in human milk, caution should be exercised when clobetasol propionate cream (emollient) is administered to nursing woman.

Pediatric Use

Safety and effectiveness of clobetasol propionate cream (emollient) in pediatric patients have not been established. Use in pediatric patients under 12 years of age is not recommended. For continued use beyond 2 consecutive weeks, the safety of clobetasol propionate cream (emollient) has not been studied. Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of HPA axis suppression and Cushing's syndrome when they are treated with topical corticosteroids. They are therefore also at greater risk of adrenal insufficiency during or after withdrawal of treatment. Adverse effects including striae have been reported with inappropriate use of topical corticosteroids in infants and children.

HPA axis suppression, Cushing's syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in children receiving topical corticosteroids. Manifestations of adrenal suppression in children include low plasma cortisol levels and absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.

Clinical studies of clobetasol propionate emollient cream, 0.05% in US clinical trials did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious.

Adverse Reactions

In controlled trials with all clobetasol propionate formulations, the following adverse reactions have been reported: burning/stinging, pruritus, irritation, erythema, folliculitis, cracking and fissuring of the skin, numbness of the fingers, tenderness in the elbow, skin atrophy, and telangiectasia. The incidence of local adverse reactions reported in the trials with clobetasol propionate cream (emollient) was <2% of patients treated with the exception of burning/stinging, which occurred in 5% of treated patients.

Cushing's syndrome has been reported in infants and adults as a result of prolonged use of other topical clobetasol propionate formulations.

The following additional local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with super-high potency corticosteroids such as clobetasol propionate cream (emollient). These reactions are listed in an approximately decreasing order of occurrence: dryness, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, striae, and miliaria.

Overdosage

Topically applied clobetasol propionate cream (emollient) can be absorbed in sufficient amounts to produce systemic effects.

Clobetasol Cream Dosage and Administration

Apply a thin layer of clobetasol propionate cream (emollient) to the affected skin areas twice daily and rub in gently and completely (see INDICATIONS AND USAGE).

Clobetasol propionate cream (emollient) is a super-high potency topical corticosteroid; therefore, treatment should be limited to 2 consecutive weeks and amounts greater than 50 g/week should not be used.

In moderate to severe plaque-type psoriasis, clobetasol propionate cream (emollient) applied to 5% to 10% of body surface area can be used up to 4 weeks. The total dosage should not exceed 50 g/week. When dosing for more than 2 weeks, any additional benefits of extending treatment should be weighed against the risk of HPA suppression. As with other highly active corticosteroids, therapy should be discontinued when control has been achieved. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary. Treatment beyond 4 consecutive weeks is not recommended. Use in pediatric patients under 16 years of age has not been studied.

Clobetasol propionate cream (emollient) should not be used with occlusive dressings.

How is Clobetasol Cream Supplied

Clobetasol propionate cream (emollient) USP, 0.05% is supplied in 15g, 30g, and 60g tubes.

Store at 20°- 25°C (68°- 77°F) [see USP Controlled Room Temperature]. Do not refrigerate.

Mfd. by: Taro Pharmaceuticals Inc., Brampton, Ontario, Canada L6T 1C1

Revised: September, 2004

PK-3030-1 136

PRINCIPAL DISPLAY PANEL - 15 g Tube Carton

NDC 51672-1297-1

15 g

Clobetasol Propionate

Cream (Emollient) USP, 0.05%

FOR DERMATOLOGIC USE ONLY.

NOT FOR OPHTHALMIC USE.

Rx only

Keep this and all medications out of the reach of children.

TARO

CLOBETASOL PROPIONATE  clobetasol propionate  cream

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 51672-1297 Route of Administration TOPICAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Clobetasol Propionate (Clobetasol) Clobetasol Propionate 0.5 mg  in 1 g

Inactive Ingredients Ingredient Name Strength ceteth-20   cetostearyl alcohol   citric acid monohydrate   dimethicone 350   imidurea   isopropyl myristate   propylene glycol   water   sodium citrate

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 51672-1297-1 1 TUBE In 1 CARTON contains a TUBE 1 15 g In 1 TUBE This package is contained within the CARTON (51672-1297-1) 2 51672-1297-2 1 TUBE In 1 CARTON contains a TUBE 2 30 g In 1 TUBE This package is contained within the CARTON (51672-1297-2) 3 51672-1297-3 1 TUBE In 1 CARTON contains a TUBE 3 60 g In 1 TUBE This package is contained within the CARTON (51672-1297-3)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA075633	05/17/2000

Labeler - Taro Pharmaceuticals U.S.A., Inc. (145186370)

Establishment
Name	Address	ID/FEI	Operations
Taro Pharmaceuticals Inc.		206263295	MANUFACTURE

Revised: 09/2011Taro Pharmaceuticals U.S.A., Inc.

More Clobetasol Cream resources

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

Compare Clobetasol Cream with other medications

• Anal Itching
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Zemaira

Generic Name: alpha 1-proteinase inhibitor (AL fa 1-PRO tee nase in HIB i tor)

Brand Names: Aralast, Aralast NP, Prolastin, Zemaira

What is alpha 1-proteinase inhibitor?

Alpha 1-proteinase inhibitor is a protein, also called alpha 1-antitrypsin. This protein occurs naturally in the body and is important for preventing the breakdown of tissues in the lungs.

In people who lack the alpha 1-antitrypsin protein, breakdown of lung tissues can lead to emphysema (damage to the air sacs in the lungs).

Alpha 1-proteinase inhibitor is used to treat alpha 1-antitrypsin deficiency in people who have symptoms of emphysema.

Alpha 1-antitrypsin deficiency is a genetic (inherited) disorder and alpha 1-proteinase inhibitor will not cure this condition.

Alpha 1-proteinase inhibitor may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about alpha 1-proteinase inhibitor?

You should not use this medication if you have ever had an allergic reaction to alpha 1-proteinase inhibitor, or if you have an IgA deficiency or antibody against IgA.

Do not self-inject this medicine if you do not fully understand how to give the injection and properly dispose of needles, IV tubing, and other items used in giving the medicine.

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

You will most likely receive your first few doses of this medication in a hospital or clinic setting where your vital signs can be watched closely in case the medication causes serious side effects.

Alpha 1-proteinase inhibitor is made from human plasma (part of the blood) and may contain viruses and other infectious agents that can cause disease. Although donated human plasma is screened, tested, and treated to reduce the risk of it containing anything that could cause disease, there is still a small possibility it could transmit disease. Talk with your doctor about the risks and benefits of using this medication.

What should I discuss with my health care provider before using alpha 1-proteinase inhibitor?

You should not use this medication if you have ever had an allergic reaction to alpha 1-proteinase inhibitor, or if you have an IgA deficiency or antibody against IgA.

Before you receive alpha 1-proteinase inhibitor, tell your doctor about all of your medication conditions.

FDA pregnancy category C. Alpha 1-proteinase inhibitor 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 alpha 1-proteinase inhibitor 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.

Alpha 1-proteinase inhibitor is made from human plasma (part of the blood) and may contain viruses and other infectious agents that can cause disease. Although donated human plasma is screened, tested, and treated to reduce the risk of it containing anything that could cause disease, there is still a small possibility it could transmit disease. Talk with your doctor about the risks and benefits of using this medication.

How should I use alpha 1-proteinase inhibitor?

Alpha 1-proteinase inhibitor is usually given once per week. Use this medication exactly as prescribed by your doctor. Do not use it in larger amounts or for longer than recommended. Follow the directions on your prescription label.

Alpha 1-proteinase inhibitor is given as an injection through a needle placed into a vein. Your doctor, nurse, or other healthcare provider will give you this injection. You may be shown how to use your medicine at home. Do not self-inject this medicine if you do not fully understand how to give the injection and properly dispose of needles, IV tubing, and other items used in giving the medicine.

You will most likely receive your first few doses of this medication in a hospital or clinic setting where your vital signs can be watched closely in case the medication causes serious side effects.

You will need to mix alpha 1-proteinase inhibitor with a liquid (diluent) before using it. If you are using the injections at home, be sure you understand how to properly mix and store the medication. After mixing alpha 1-proteinase inhibitor with a diluent, you must use the medicine within 3 hours. It is best not to mix your alpha 1-proteinase inhibitor dose until you are ready to give the injection. The mixture should look clear or slightly yellow-green and may have a few small particles in it.

Do not shake the medication vial (bottle). Vigorous shaking can ruin the medicine. You may gently swirl the medication while mixing.

Use each disposable needle only one time. Throw away used needles in a puncture-proof container (ask your pharmacist where you can get one and how to dispose of it). Keep this container out of the reach of children and pets.

Store the Aralast brand of this medication in the refrigerator. Do not freeze. Store Prolastin or Zemaira at cool room temperature (no warmer than 77 degrees F), away from moisture and heat. Aralast may also be stored at room temperature but you must use it within 30 days after removing it from the refrigerator.

Do not use this medication after the expiration date on the medicine label has passed.

What happens if I miss a dose?

Call your doctor for instructions if you miss a dose of alpha 1-proteinase inhibitor.

What happens if I overdose?

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

An overdose of alpha 1-proteinase inhibitor is not expected to produce life-threatening symptoms.

What should I avoid while taking alpha 1-proteinase inhibitor?

Follow your doctor's instructions about any restrictions on food, beverages, or activity while you are using alpha 1-proteinase inhibitor.

Alpha 1-proteinase inhibitor side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; wheezing, difficulty breathing; feeling like you might pass out; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have a serious side effect such as:

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  chest pain, severe headache, buzzing in your ears, uneven heartbeats;

  
  


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  fast heart rate;

  
  


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  problems with vision; or

  
  


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  fever, chills, runny nose, skin rash, and joint pain.

  
  

Less serious side effects may include:

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  drowsiness, dizziness, weakness;

  
  


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  cough, sore throat, stuffy nose;

  
  


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  pain or bleeding where the medication was injected;

  
  


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  warmth, redness, or tingly feeling under your skin;

  
  


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  nausea, diarrhea, stomach pain;

  
  


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  headache; or

  
  


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  mild itching.

  
  

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

What other drugs will affect alpha 1-proteinase inhibitor?

There may be other drugs that can interact with alpha 1-proteinase inhibitor. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

More Zemaira resources

• Zemaira Side Effects (in more detail)
• Zemaira Use in Pregnancy & Breastfeeding
• Zemaira Support Group
• 2 Reviews for Zemaira - Add your own review/rating

• Zemaira Prescribing Information (FDA)


• Zemaira MedFacts Consumer Leaflet (Wolters Kluwer)


• Zemaira Advanced Consumer (Micromedex) - Includes Dosage Information


• Zemaira Consumer Overview


• Aralast NP Prescribing Information (FDA)


• Glassia Consumer Overview


• Glassia Prescribing Information (FDA)


• Glassia Solution MedFacts Consumer Leaflet (Wolters Kluwer)


• Prolastin-C Prescribing Information (FDA)

Compare Zemaira with other medications

• Alpha-1 Proteinase Inhibitor Deficiency

Where can I get more information?

• Your pharmacist can provide more information about alpha 1-proteinase inhibitor.

See also: Zemaira side effects (in more detail)