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About Formulary Kits

Welcome to Formkit.com’s Formulary Kits Online

We are pleased to provide you with online formulary kits, brought to you by Formkit.com. These kits, listed in alphabetical order, cover numerous therapeutic categories. We have provided for your review the latest information about new indications and products cleared for marketing by the FDA.

Abilify Maintena™

(aripiprazole) for extended-release injectable suspension

Abilify Maintena(aripiprazole) for Extended-Release Injectable Suspension

INDICATION
Abilify Maintena is an atypical antipsychotic indicated for the treatment of schizophrenia.

  • Efficacy was demonstrated in a placebo-controlled, randomized-withdrawal maintenance trial in patients with schizophrenia and additional support for efficacy was derived from oral aripiprazole trials.

IMPORTANT SAFETY INFORMATION      

Increased Mortality in Elderly Patients with Dementia-Related Psychosis

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk (1.6 to 1.7 times) of death compared to placebo (4.5% vs 2.6%, respectively). Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Abilify Maintena is not approved for the treatment of patients with dementia-related psychosis. 

Contraindication: Known hypersensitivity reaction to aripiprazole. Reactions have ranged from pruritus/urticaria to anaphylaxis.

Cerebrovascular Adverse Events, Including Stroke: Increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, have been reported in clinical trials of elderly patients with dementia-related psychosis treated with oral aripiprazole.

Neuroleptic Malignant Syndrome (NMS): A potentially fatal symptom complex sometimes referred to as NMS may occur with administration of antipsychotic drugs, including Abilify Maintena. Rare cases of NMS occurred during aripiprazole treatment. Signs and symptoms of NMS include hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (e.g., irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. The management of NMS should include: 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy; 2) intensive symptomatic treatment and medical monitoring; and 3) treatment of any concomitant serious medical problems for which specific treatments are available.

Tardive Dyskinesia (TD): The risk of developing TD (a syndrome of abnormal, involuntary movements) and the potential for it to become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic increase. The syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses. Prescribing should be consistent with the need to minimize TD. There is no known treatment for established TD, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn.

Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that include:

Hyperglycemia/Diabetes Mellitus: Hyperglycemia, in some cases extreme and associated with ketoacidosis, coma, or death, has been reported in patients treated with atypical antipsychotics including aripiprazole. Patients with diabetes should be regularly monitored for worsening of glucose control; those with risk factors for diabetes should undergo baseline and periodic fasting blood glucose testing. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia should also undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the suspect drug.

Dyslipidemia: Undesirable alterations in lipids have been observed in patients treated with atypical antipsychotics. There were no significant differences between aripiprazole- and placebo-treated patients in the proportion with changes from normal to clinically significant levels for fasting/nonfasting total cholesterol, fasting triglycerides, fasting low-density lipoproteins (LDLs), and fasting/nonfasting high-density lipoproteins (HDLs).

Weight Gain: Weight gain has been observed. Clinical monitoring of weight is recommended.

Orthostatic Hypotension: Aripiprazole may cause orthostatic hypotension. Abilify Maintena should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, or conditions which would predispose them to hypotension.

Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia, neutropenia, and agranulocytosis have been reported. Patients with a history of clinically significant low white blood cell (WBC) count or drug-induced leukopenia/neutropenia should have their complete blood count monitored frequently during the first few months of therapy while receiving Abilify Maintena. In such patients, consider discontinuation of Abilify Maintena at the first sign of a clinically significant decline in WBC count in the absence of other causative factors.

Seizures/Convulsions: Abilify Maintena should be used with caution in patients with a history of seizures or with conditions that lower the seizure threshold.

Potential for Cognitive and Motor Impairment: Abilify Maintena may impair judgment, thinking, or motor skills. Instruct patients to avoid operating hazardous machinery including automobiles until they are certain Abilify Maintena does not affect them adversely.

Body Temperature Regulation: Disruption of the body’s ability to reduce core body temperature has been attributed to antipsychotic agents. Advise patients regarding appropriate care in avoiding overheating and dehydration. Appropriate care is advised for patients who may exercise strenuously, may be exposed to extreme heat, receive concomitant medication with anticholinergic activity, or are subject to dehydration.

Dysphagia: Esophageal dysmotility and aspiration have been associated with Abilify Maintena; use caution in patients at risk for aspiration pneumonia.

Alcohol: Advise patients to avoid alcohol while taking Abilify Maintena.

Concomitant Medication: Dosage adjustments are recommended in patients who are CYP2D6 poor metabolizers and in patients taking concomitant CYP3A4 inhibitors or CYP2D6 inhibitors for greater than 14 days. If the CYP3A4 inhibitor or CYP2D6 inhibitor is withdrawn, the Abilify Maintena dosage may need to be increased. Avoid the concomitant use of CYP3A4 inducers with Abilify Maintena for greater than 14 days because the blood levels of aripiprazole are decreased and may be below the effective levels. Dosage adjustments are not recommended for patients with concomitant use of CYP3A4 inhibitors, CYP2D6 inhibitors or CYP3A4 inducers for less than 14 days.

Most commonly observed adverse reaction: The safety profile of Abilify Maintena is expected to be similar to that of oral aripiprazole. In patients who tolerated and responded to oral aripiprazole and single-blind Abilify Maintena and were then randomized to receive Abilify Maintena or placebo injections, the incidence of adverse reactions was similar between the two treatment groups. The adverse reaction ≥ 5% incidence and at least twice the rate of placebo for oral aripiprazole vs placebo, respectively, was:

• Akathisia (8% vs 4%) in adult patients with schizophrenia.

Injection Site Reactions: In the open-label, stabilization phase of a study with Abilify Maintena in patients with schizophrenia, the percent of patients reporting any injection site-related adverse reaction was 6.3% for Abilify Maintena-treated patients.

Dystonia is a class effect of antipsychotic drugs. Symptoms of dystonia may occur in susceptible individuals during the first days of treatment and at low doses.

Pregnancy/Nursing: Based on animal data, may cause fetal harm. Abilify Maintena should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Aripiprazole is excreted in human breast milk. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Click here for FULL PRESCRIBING INFORMATION, including Boxed WARNING, for Abilify Maintena.

 


© 2013 Otsuka America Pharmaceutical, Inc., Rockville, MD

February 2013 0912W-4969B

BYDUREON® Pen

(exenatide extended-release for injectable suspension)

Indication and Important Limitations of Use for BYDUREON® Pen (exenatide extended-release for injectable suspension)

BYDUREON is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

  • Because of the uncertain relevance of the rat thyroid C-cell tumor findings to humans, prescribe only to patients for whom potential benefits are considered to outweigh potential risk.
  • Not recommended as first-line therapy for patients who have inadequate glycemic control on diet and exercise.
  • Not a substitute for insulin, should not be used in patients with type 1 diabetes or diabetic ketoacidosis, and cannot be recommended for use with insulin.
  • BYDUREON and BYETTA® (exenatide) injection both contain the same active ingredient, exenatide, and should not be used together.
  • Exenatide has been associated with acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, based on postmarketing data. It is unknown whether patients with a history of pancreatitis are at increased risk for pancreatitis while using BYDUREON; consider other antidiabetic therapies for these patients.

Important Safety Information for BYDUREON Pen

WARNING: RISK OF THYROID C-CELL TUMORS

Exenatide extended-release causes an increased incidence in thyroid C-cell tumors at clinically relevant exposures in rats compared to controls. It is unknown whether BYDUREON causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as human relevance could not be determined by clinical or nonclinical studies. BYDUREON is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Routine serum calcitonin or thyroid ultrasound monitoring is of uncertain value in patients treated with BYDUREON. Patients should be counseled regarding the risk and symptoms of thyroid tumors.

Contraindications

  • Patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
  • Patients with prior serious hypersensitivity reactions to exenatide or to any of the product components.

Warnings and Precautions

  • Pancreatitis: Based on postmarketing data, exenatide has been associated with acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. After initiation of BYDUREON, observe patients carefully for pancreatitis (persistent severe abdominal pain, sometimes radiating to the back, with or without vomiting). If pancreatitis is suspected, BYDUREON should be discontinued promptly and should not be restarted if pancreatitis is confirmed.
  • Hypoglycemia: Increased risk of hypoglycemia when used in combination with a sulfonylurea (SU). Clinicians may consider reducing the SU dose to minimize risk of hypoglycemia. It is possible that use of BYDUREON with other glucose-independent insulin secretagogues (eg, meglitinides) could increase the risk of hypoglycemia.
  • Renal Impairment: Should not be used in patients with severe renal impairment or end-stage renal disease. Use with caution in patients with renal transplantation or moderate renal failure. Postmarketing reports of altered renal function with exenatide, including increased serum creatinine, renal impairment, worsened chronic renal failure, and acute renal failure, sometimes requiring hemodialysis and kidney transplantation.
  • Gastrointestinal Disease: Because exenatide is commonly associated with gastrointestinal adverse reactions, BYDUREON is not recommended in patients with severe gastrointestinal disease (eg, gastroparesis).
  • Immunogenicity: Patients may develop antibodies to exenatide. In 5 registration trials, attenuated glycemic response was associated in 6% of BYDUREON-treated patients with antibody formation. If worsening of or failure to achieve adequate glycemic control occurs, consider alternative antidiabetic therapy.
  • Hypersensitivity: Postmarketing reports of serious hypersensitivity reactions (eg, anaphylaxis and angioedema). If this occurs, patients should discontinue BYDUREON and other suspect medications and promptly seek medical advice.
  • Injection-Site Reactions: Postmarketing reports of serious injection-site reactions (eg, abscess, cellulitis, and necrosis), with or without subcutaneous nodules, with the use of BYDUREON.
  • Macrovascular Outcomes: No clinical studies establishing conclusive evidence of macrovascular risk reduction with BYDUREON or any other antidiabetic drug.

Withdrawals

  • In 5 comparator-controlled, 24- to 30-week BYDUREON trials, the incidence of withdrawal due to adverse events was 4.9% for BYDUREON, 4.9% for BYETTA, and 2.0% for other comparators. The most common adverse reactions leading to withdrawal for BYDUREON, BYETTA, and comparators respectively were nausea (0.5%, 1.5%, 0.3%), injection-site nodule (0.5%, 0.0%, 0.0%), diarrhea (0.3%, 0.4%, 0.3%), injection-site reaction (0.2%, 0.0%, 0.0%), and headache (0.2%, 0.0%, 0.0%). One percent of BYDUREON patients withdrew due to injection-site adverse reactions.

Most Common Adverse Reactions (≥5%)

  • BYDUREON vs BYETTA:
    • 24-week trial: nausea (14% vs 35%), diarrhea (9.3% vs 4.1%), injection-site erythema (5.4% vs 2.4%).
    • 30-week trial: nausea (27% vs 33.8%), diarrhea (16.2% vs 12.4%), vomiting (10.8% vs 18.6%), injection-site pruritus (18.2% vs 1.4%), constipation (10.1% vs 6.2%), gastroenteritis viral (8.8% vs 5.5%), gastroesophageal reflux disease (7.4% vs 4.1%), dyspepsia (7.4% vs 2.1%), injection-site erythema (7.4% vs 0.0%), fatigue (6.1% vs 3.4%), headache (6.1% vs 4.8%), injection-site hematoma (5.4% vs 11.0%).
  • BYDUREON vs titrated insulin glargine: nausea (12.9% vs 1.3%), headache (9.9% vs 7.6%), diarrhea (9.4% vs 4.0%), injection-site nodule (6.0% vs 0.0%).
  • Combination trial vs sitagliptin and pioglitazone: nausea (24.4% vs 9.6% and 4.8%), diarrhea (20.0% vs 9.6% and 7.3%), vomiting (11.3% vs 2.4% and 3.0%), headache (9.4% vs 9.0% and 5.5%), constipation (6.3% vs 3.6% and 1.2%), fatigue (5.6% vs 0.6% and 3.0%), dyspepsia (5.0% vs 3.6% and 2.4%), decreased appetite (5.0% vs 1.2% and 0.0%), injection-site pruritus (5.0% vs 4.8% and 1.2%).
  • Monotherapy trial vs sitagliptin, pioglitazone, and metformin: nausea (11.3% vs 3.7%, 4.3%, and 6.9%), diarrhea (10.9% vs 5.5%, 3.7%, and 12.6%), injection-site nodule (10.5% vs 6.7%, 3.7%, and 10.2%), constipation (8.5% vs 2.5%, 1.8%, and 3.3%), headache (8.1% vs 9.2%, 8.0%, and 12.2%), dyspepsia (7.3% vs 1.8%, 4.9%, and 3.3%).
  • Hypoglycemia: No major hypoglycemia was reported for BYDUREON- or comparator-treated patients in five 24- to 30-week trials. Minor hypoglycemia incidences for BYDUREON vs comparator-treated patients were as follows: 24-week trial vs BYETTA: with SU, 12.5% vs 11.8%; without SU, 0.0% for both; 30-week trial vs BYETTA: with SU, 14.5% vs 15.4%; without SU, 0.0% vs 1.1%; monotherapy trial vs sitagliptin, pioglitazone, and metformin: 2.0% vs 0.0% (all comparators); combination trial vs sitagliptin and pioglitazone: 1.3% vs 3.0% and 1.2%; vs titrated insulin glargine, with SU, 20.0% vs 43.9%; without SU, 3.7% vs 19.1%.
  • Injection-site reactions were observed more frequently in BYDUREON-treated patients (17.1%) vs patients treated with BYETTA (12.7%), titrated insulin glargine (1.8%), or placebo injection (6.4%-13.0%). Injection-site reactions were observed in 14.2% of antibody-positive patients vs 3.1% of antibody-negative patients, with higher incidence in those with higher-titer antibodies. BYETTA-treated patients had similar incidence between antibody-positive and antibody-negative patients (5.8% vs 7.0%). Subcutaneous injection-site nodules may occur with the use of BYDUREON.

Drug Interactions

  • Oral Medications: BYDUREON slows gastric emptying and can reduce the rate of absorption of orally administered drugs. Use with caution with oral medications.
  • Warfarin: Postmarketing reports with exenatide of increased international normalized ratio (INR) sometimes associated with bleeding with concomitant use of warfarin. Monitor INR frequently until stable upon initiation or alteration of BYDUREON.

Use in Specific Populations

  • Pregnant and Nursing Women: Based on animal data, BYDUREON may cause fetal harm and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. To report drug exposure during pregnancy call 1-800-633-9081. When administered to a nursing woman, a decision should be made whether to discontinue nursing or to discontinue BYDUREON.
  • Pediatric Patients: Use in pediatric patients is not recommended as safety and effectiveness have not been established.

Please click here for US Full Prescribing Information and click here for Medication Guide for BYDUREON Pen 2 mg, including Boxed WARNING regarding risk of thyroid C-cell tumors.

3011302    Last Updated 6/14

DUAVEE™

(Conjugated Estrogens/ Bazedoxifene)

IMPORTANT SAFETY INFORMATION

Women taking DUAVEE should not be taking progestins, additional estrogens, or additional estrogen agonists/antagonists.

There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. DUAVEE contains bazedoxifene, an estrogen agonist/antagonist that reduces the risk of endometrial hyperplasia that can occur with estrogens and which may be a precursor to endometrial cancer. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.

Estrogen therapy should not be used for the prevention of cardiovascular disease or dementia.

The Women’s Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT). Should either of these occur or be suspected, DUAVEE should be discontinued immediately.

The WHI Memory Study (WHIMS) estrogen-alone ancillary study of WHI reported an increased risk of probable dementia in postmenopausal women 65 years of age and older.

Estrogen agonists/antagonists, including bazedoxifene, and estrogens individually are known to increase the risk of venous thromboembolism (VTE).

DUAVEE should not be used in women with undiagnosed abnormal uterine bleeding; known, suspected, or past history of breast cancer or estrogen-dependent neoplasia; active or past history of venous or arterial thromboembolism; hypersensitivity to estrogens, bazedoxifene, or any ingredients; known hepatic impairment or disease; known thrombophilic disorders. Women who are or may become pregnant and nursing mothers should not use DUAVEE.

The use of estrogen alone has been reported to result in an increase in abnormal mammograms requiring further evaluation. The effect of treatment with DUAVEE on the risk of breast and ovarian cancer is unknown.

Estrogens increase the risk of gallbladder disease. Discontinue estrogen if loss of vision, severe hypertriglyceridemia, or cholestatic jaundice occurs.

Adverse reactions more common in the DUAVEE treatment group in four placebo-controlled studies were muscle spasms, nausea, diarrhea, dyspepsia, abdominal pain upper, oropharyngeal pain, dizziness, and neck pain.

INDICATIONS

DUAVEE is indicated in women with a uterus for the treatment of moderate to severe vasomotor symptoms associated with menopause and the prevention of postmenopausal osteoporosis.

When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis, and non-estrogen medication should be carefully considered. Use DUAVEE for the shortest duration consistent with treatment goals and risks for the individual woman. Postmenopausal women should be re-evaluated periodically, as clinically appropriate, to determine if treatment is still necessary.

Please see full Prescribing Information including BOXED WARNING.

ELIQUIS®

(apixaban) tablets

Indications

ELIQUIS is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.

ELIQUIS is indicated for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients who have undergone hip or knee replacement surgery.

ELIQUIS is indicated for the treatment of DVT and PE, and to reduce the risk of recurrent DVT and PE following initial therapy.

Important Safety Information

WARNING: (A) PREMATURE DISCONTINUATION OF ELIQUIS INCREASES THE RISK OF THROMBOTIC EVENTS, (B) SPINAL/EPIDURAL HEMATOMA

(A) Premature discontinuation of any oral anticoagulant, including ELIQUIS, increases the risk of thrombotic events. If anticoagulation with ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant.

(B) Epidural or spinal hematomas may occur in patients treated with ELIQUIS who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include:

  • use of indwelling epidural catheters
  • concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants
  • a history of traumatic or repeated epidural or spinal punctures
  • a history of spinal deformity or spinal surgery
  • optimal timing between the administration of ELIQUIS and neuraxial procedures is not known

Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary.

Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated.

CONTRAINDICATIONS

  • Active pathological bleeding
  • Severe hypersensitivity reaction to ELIQUIS (e.g., anaphylactic reactions)

WARNINGS AND PRECAUTIONS

  • Increased Risk of Thrombotic Events after Premature Discontinuation: Premature discontinuation of any oral anticoagulant, including ELIQUIS, in the absence of adequate alternative anticoagulation increases the risk of thrombotic events. An increased rate of stroke was observed during the transition from ELIQUIS to warfarin in clinical trials in atrial fibrillation patients. If ELIQUIS is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant
  • Bleeding Risk: ELIQUIS increases the risk of bleeding and can cause serious, potentially fatal, bleeding.
    • Concomitant use of drugs affecting hemostasis increases the risk of bleeding, including aspirin and other antiplatelet agents, other anticoagulants, heparin, thrombolytic agents, SSRIs, SNRIs, and NSAIDs.
    • Advise patients of signs and symptoms of blood loss and to report them immediately or go to an emergency room. Discontinue ELIQUIS in patients with active pathological hemorrhage.
    • There is no established way to reverse the anticoagulant effect of apixaban, which can be expected to persist for at least 24 hours after the last dose (i.e., about two half-lives). A specific antidote for ELIQUIS is not available.
  • Spinal/Epidural Anesthesia or Puncture: Patients treated with Eliquis undergoing spinal/epidural anesthesia or puncture may develop an epidural or spinal hematoma which can result in long-term or permanent paralysis.

    The risk of these events may be increased by the postoperative use of indwelling epidural catheters or the concomitant use of medicinal products affecting hemostasis. Indwelling epidural or intrathecal catheters should not be removed earlier than 24 hours after the last administration of ELIQUIS. The next dose of ELIQUIS should not be administered earlier than 5 hours after the removal of the catheter. The risk may also be increased by traumatic or repeated epidural or spinal puncture. If traumatic puncture occurs, delay the administration of ELIQUIS for 48 hours.

    Monitor patients frequently and if neurological compromise is noted, urgent diagnosis and treatment is necessary. Physicians should consider the potential benefit versus the risk of neuraxial intervention in Eliquis patients.
  • Prosthetic Heart Valves: The safety and efficacy of ELIQUIS have not been studied in patients with prosthetic heart valves and is not recommended in these patients.
  • Acute PE in Hemodynamically Unstable Patients or Patients who Require Thrombolysis or Pulmonary Embolectomy: Initiation of ELIQUIS is not recommended as an alternative to unfractionated heparin for the initial treatment of patients with PE who present with hemodynamic instability or who may receive thrombolysis or pulmonary embolectomy.

ADVERSE REACTIONS

  • The most common and most serious adverse reactions reported with ELIQUIS were related to bleeding.

TEMPORARY INTERRUPTION FOR SURGERY AND OTHER INTERVENTIONS

  • ELIQUIS should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding. ELIQUIS should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding or where the bleeding would be noncritical in location and easily controlled. Bridging anticoagulation during the 24 to 48 hours after stopping ELIQUIS and prior to the intervention is not generally required. ELIQUIS should be restarted after the surgical or other procedures as soon as adequate hemostasis has been established.

DRUG INTERACTIONS

  • Strong Dual Inhibitors of CYP3A4 and P-gp: Inhibitors of CYP3A4 and P-gp increase exposure to apixaban and increase the risk of bleeding. For patients receiving ELIQUIS doses greater than 2.5 mg twice daily, the dose of ELIQUIS should be decreased by 50% when it is coadministered with drugs that are strong dual inhibitors of CYP3A4 and P-gp (e.g., ketoconazole, itraconazole, ritonavir, or clarithromycin). For patients receiving ELIQUIS at a dose of 2.5 mg twice daily, avoid coadministration with strong dual inhibitors of CYP3A4 and P-gp.
  • Strong Dual Inducers of CYP3A4 and P-gp: Avoid concomitant use of ELIQUIS with strong dual inducers of CYP3A4 and P-gp (e.g., rifampin, carbamazepine, phenytoin, St. John’s wort) because such drugs will decrease exposure to apixaban and increase the risk of stroke and other thromboembolic events.
  • Anticoagulants and Antiplatelet Agents: Coadministration of antiplatelet agents, fibrinolytics, heparin, aspirin, and chronic NSAID use increases the risk of bleeding. APPRAISE-2, a placebo-controlled clinical trial of apixaban in high-risk post-acute coronary syndrome patients treated with aspirin or the combination of aspirin and clopidogrel, was terminated early due to a higher rate of bleeding with apixaban compared to placebo.

PREGNANCY CATEGORY B

  • There are no adequate and well-controlled studies of ELIQUIS in pregnant women. Treatment is likely to increase the risk of hemorrhage during pregnancy and delivery. ELIQUIS should be used during pregnancy only if the potential benefit outweighs the potential risk to the mother and fetus.

ELIQUIS is available in 2.5 and 5 mg tablets.

Please see Full Prescribing Information, including Boxed WARNINGS.

ELIQUIS is a registered trademark of Bristol-Myers Squibb Company.

© 2014 Bristol-Myers Squibb Company. All rights reserved.

Farxiga™

(dapagliflozin)

INDICATION AND LIMITATION OF USE FOR Farxiga™ (dapagliflozin)

FARXIGA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

FARXIGA is not recommended for patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.

IMPORTANT SAFETY INFORMATION FOR FARXIGA

Contraindications

  • History of a serious hypersensitivity reaction to FARXIGA
  • Severe renal impairment, end stage renal disease, or patients on dialysis

Warnings and Precautions

  • Hypotension: FARXIGA causes intravascular volume contraction. Symptomatic hypotension can occur after initiating FARXIGA, particularly in patients with impaired renal function (eGFR <60 mL/min/1.73 m2), elderly patients, or patients on loop diuretics. Before initiating FARXIGA in patients with one or more of these characteristics, assess and correct volume status. After initiating therapy, monitor for signs and symptoms of hypotension.
  • Impairment in Renal Function: FARXIGA increases serum creatinine and decreases eGFR. Elderly patients and patients with impaired renal function may be more susceptible to these changes. Adverse reactions related to renal function can occur after initiating FARXIGA. Before initiating FARXIGA, evaluate renal function and monitor periodically thereafter. Discontinue FARXIGA when eGFR is persistently <60 mL/min/1.73 m2.
  • Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues: Insulin and insulin secretagogues are known to cause hypoglycemia. FARXIGA can increase the risk of hypoglycemia when combined with these agents. Consider a lower dose of insulin or the insulin secretagogue to reduce the risk of hypoglycemia when used in combination with FARXIGA.
  • Genital Mycotic Infections: FARXIGA increases the risk of genital mycotic infections. Patients with a history of genital mycotic infections were more likely to develop genital mycotic infections. Monitor and treat appropriately.
  • Increases in Low-Density Lipoprotein Cholesterol (LDL-C): Increases in LDL-C occur with FARXIGA. After initiating FARXIGA, monitor LDL-C and treat per standard of care.
  • Bladder Cancer: Across 22 clinical studies, newly diagnosed cases of bladder cancer were reported in 0.17% of FARXIGA-treated patients and 0.03% of placebo/comparator-treated patients. After excluding patients in whom exposure to study drug was <1 year at the time of diagnosis of bladder cancer, there were 4 cases with FARXIGA and no cases with placebo/comparator. Bladder cancer risk factors and hematuria (a potential indicator of pre-existing tumors) were balanced between treatment arms at baseline. There were too few cases to determine whether the emergence of these events is related to FARXIGA.
  • There are insufficient data to determine whether FARXIGA has an effect on pre-existing bladder tumors. FARXIGA should not be used in patients with active bladder cancer. Use with caution in patients with a prior history of bladder cancer.
  • Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with FARXIGA or any other antidiabetic drug.

Adverse Reactions

  • In a pool of 12 placebo-controlled studies, the most common adverse reactions (≥5%) associated with FARXIGA 5 mg, 10 mg, and placebo respectively were female genital mycotic infections (8.4% vs 6.9% vs 1.5%), nasopharyngitis (6.6% vs 6.3% vs 6.2%), and urinary tract infections (5.7% vs 4.3% vs 3.7%).

Use in Specific Populations

  • Pregnant Women: There are no adequate and well-controlled studies of FARXIGA in pregnant women. Consider appropriate alternative therapies, especially during the second and third trimesters.
  • Nursing Mothers: It is not known whether FARXIGA is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from FARXIGA, discontinue nursing or discontinue FARXIGA.
  • Geriatric Use: A higher proportion of patients ≥65 years treated with FARXIGA had adverse reactions related to volume depletion and renal impairment or failure compared to patients treated with placebo. No FARXIGA dose change is recommended based on age.

Reference

FARXIGA [package insert]. Wilmington, DE: AstraZeneca: January 2014.

Please click here for US Full Prescribing Information and click here for Medication Guide for FARXIGA.

© 2014 AstraZeneca. All rights reserved.
FARXIGA is a trademark of the AstraZeneca group of companies.
732US14BR00871-01-01      04/14

INVOKAMET

(canagliflozin and metformin HCI)

IMPORTANT SAFETY INFORMATION

WARNING: LACTIC ACIDOSIS

Lactic acidosis is a rare but serious complication that can occur due to metformin accumulation. The risk increases with conditions such as renal impairment, sepsis, dehydration, excess alcohol intake, hepatic impairment, and acute congestive heart failure.

The onset is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress.

Laboratory abnormalities include low pH, increased anion gap, and elevated blood lactate.

If lactic acidosis is suspected, INVOKAMET™ should be discontinued and the patient hospitalized immediately.

CONTRAINDICATIONS

  • Renal impairment (ie, serum creatinine levels ≥1.5 mg/dL for males or ≥1.4 mg/dL for females, or eGFR is less than 45 mL/min/1.73m2), which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia; end stage renal disease (ESRD) or patients on dialysis
  • Acute or chronic metabolic acidosis, including diabetic ketoacidosis
  • History of a serious hypersensitivity reaction to canagliflozin or metformin

WARNINGS and PRECAUTIONS

  • Lactic Acidosis: Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with INVOKAMET™. When lactic acidosis occurs, it is fatal in approximately 50% of cases. The reported incidence of lactic acidosis in patients receiving metformin is approximately 0.03 cases/1000 patient-years (with approximately 0.015 fatal cases/1000 patient-years). Reported cases have occurred primarily in diabetic patients with significant renal insufficiency, including both intrinsic renal disease and renal hypoperfusion, often in the setting of multiple concomitant medical/surgical problems and multiple concomitant medications.

    Patients with congestive heart failure requiring pharmacologic management, particularly when accompanied by hypoperfusion and hypoxemia due to unstable or acute failure, are at increased risk of lactic acidosis. The risk of lactic acidosis increases with the degree of renal dysfunction and the patient's age. The risk of lactic acidosis may, therefore, be significantly decreased by regular monitoring of renal function in patients taking metformin. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. INVOKAMET™ treatment should not be initiated in any patient unless measurement of creatinine clearance demonstrates that renal function is not reduced. In addition, INVOKAMET™ should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration, or sepsis.

    Because impaired hepatic function has been associated with some cases of lactic acidosis, INVOKAMET™ should generally be avoided in patients with clinical or laboratory evidence of hepatic impairment. Patients should be cautioned against excessive alcohol intake when taking metformin, since alcohol potentiates the effects of metformin on lactate metabolism.

    In addition, INVOKAMET™ should be temporarily discontinued prior to any intravascular radiocontrast study, withheld for 48 hours subsequent to the procedure, and reinstituted only after renal function has been confirmed to be normal. For any surgical procedure necessitating restricted intake of food or fluids, INVOKAMET™ should be temporarily discontinued and not be initiated until the patient’s oral intake has resumed and renal function has been evaluated as normal.

    Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria or ketonemia). Lactic acidosis is a medical emergency that must be treated in a hospital setting. In a patient with lactic acidosis who is taking INVOKAMET™, the drug should be discontinued immediately and general supportive measures promptly instituted. Metformin is dialyzable (clearance of up to 170 mL/min under good hemodynamic conditions), and prompt hemodialysis is recommended to remove the accumulated metformin and correct the metabolic acidosis. Such management often results in prompt reversal of symptoms and recovery.
  • Hypotension: Canagliflozin causes intravascular volume contraction. Symptomatic hypotension can occur after initiating INVOKAMET™, particularly in patients with an eGFR <60 mL/min/1.73 m2, elderly patients, patients on either diuretics or medications that interfere with the renin-angiotensin-aldosterone system, or patients with low systolic blood pressure. Before initiating INVOKAMET™ in patients with ≥1 of these characteristics who were not already on canagliflozin, volume status should be assessed and corrected. Monitor for signs and symptoms after initiating therapy.
  • Impairment in Renal Function: Canagliflozin increases serum creatinine and decreases eGFR. Patients with hypovolemia may be more susceptible to these changes. Renal function abnormalities can occur after initiating INVOKAMET™.

    Before initiation of INVOKAMET™ therapy and at least annually thereafter, assess and verify normal renal function. In patients in whom development of renal impairment is anticipated (eg, elderly patients), assess renal function more frequently and discontinue INVOKAMET™ if evidence of renal impairment is present (ie, serum creatinine levels ≥1.5 mg/dL for males or ≥1.4 mg/dL for females, or eGFR is <45 mL/min/1.73m2).

    Use of Concomitant Medications That May Affect Renal Function or Metformin Disposition
    Monitor and adjust dose of INVOKAMET™ or concomitant drug in patients taking medication(s) that may affect renal function, result in a significant hemodynamic change, or interfere with the disposition of metformin.
  • Hyperkalemia: Canagliflozin can lead to hyperkalemia. Patients with moderate renal impairment who are taking medications that interfere with potassium excretion, such as potassium-sparing diuretics, or medications that interfere with the renin-angiotensin-aldosterone system are more likely to develop hyperkalemia.

    Monitor serum potassium levels periodically after initiating INVOKAMET™ in patients with impaired renal function and in patients predisposed to hyperkalemia due to medications or other medical conditions.
  • Impaired Hepatic Function: Metformin use in patients with impaired hepatic function has been associated with some cases of lactic acidosis. Therefore, INVOKAMET™ is not recommended in patients with clinical or laboratory evidence of hepatic impairment.
  • Use With Medications Known to Cause Hypoglycemia

    Canagliflozin
    Canagliflozin can increase the risk of hypoglycemia when combined with insulin or an insulin secretagogue. A lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with INVOKAMET™.

    Metformin
    Hypoglycemia does not occur in patients receiving metformin alone under usual circumstances of use, but could occur when caloric intake is deficient, when strenuous exercise is not compensated by caloric supplementation, or when used concomitantly with other glucose-lowering agents (such as sulfonylureas or insulin) or ethanol. Elderly, debilitated, or malnourished patients, and those with adrenal or pituitary insufficiency or alcohol intoxication, are particularly susceptible to hypoglycemic effects. Hypoglycemia may be difficult to recognize in the elderly and in people who are taking beta-adrenergic blocking drugs. Monitor for a need to lower the dose of INVOKAMET™ to minimize the risk of hypoglycemia in these patients.
  • Genital Mycotic Infections: Canagliflozin increases risk of genital mycotic infections. Patients with a history of these infections and uncircumcised males were more likely to develop these infections. Monitor and treat appropriately.
  • Hypersensitivity Reactions: Hypersensitivity reactions (eg, generalized urticaria), some serious, were reported with canagliflozin; these reactions generally occurred within hours to days after initiation. If reactions occur, discontinue INVOKAMET™; treat per standard of care and monitor until signs and symptoms resolve.
  • Vitamin B12 Levels: In clinical trials of metformin, a decrease to subnormal levels of previously normal serum vitamin B12 levels, without clinical manifestations, was observed in approximately 7% of metformin-treated patients. The decrease in vitamin B12 levels appears to be rapidly reversible with discontinuation of metformin or vitamin B12 supplementation. Measure hematologic parameters on an annual basis in patients on INVOKAMET™ and investigate and treat if abnormalities occur. Patients with inadequate vitamin B12 or calcium intake or absorption may be predisposed to develop subnormal vitamin B12 levels.
  • Alcohol Intake: Alcohol is known to potentiate the effect of metformin on lactate metabolism. Warn patients against excessive alcohol intake while receiving INVOKAMET™.
  • Hypoxic States: Cardiovascular collapse (shock) from whatever cause (eg, acute congestive heart failure, acute myocardial infarction, or other conditions characterized by hypoxemia) have been associated with lactic acidosis and may also cause prerenal azotemia. When such events occur, promptly discontinue INVOKAMET™.
  • Increases in Low-Density Lipoprotein (LDL-C): Dose-related increases in LDL-C can occur with canagliflozin. Monitor LDL-C and treat per standard of care after initiating INVOKAMET™.
  • Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with canagliflozin or metformin or any other antidiabetic drug.

DRUG INTERACTIONS

  • Drug Interactions With Metformin

    Cationic Drugs
    Cationic drugs (eg, amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, or vancomycin) that are eliminated by renal tubular secretion theoretically have the potential for interaction with metformin by competing for common renal tubular transport systems. Although such interactions remain theoretical (except with cimetidine), careful patient monitoring and dose adjustment of INVOKAMET™ and/or the interfering drug is recommended in patients who are taking cationic medications that are excreted via the proximal renal tubular secretory system.

    Carbonic Anhydrase Inhibitors
    Topiramate or other carbonic anhydrase inhibitors (eg, zonisamide, acetazolamide, or dichlorphenamide) frequently decrease serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of these drugs may induce metabolic acidosis. Use these drugs with caution in patients treated with metformin, as the risk of lactic acidosis may increase.

    Drugs Affecting Glycemic Control
    Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. When such drugs are administered to a patient receiving INVOKAMET™, the patient should be closely observed for loss of blood glucose control. When such drugs are withdrawn from a patient receiving INVOKAMET™, the patient should be observed closely for hypoglycemia.
  • Drug Interactions With Canagliflozin

    UGT Enzyme Inducers
    Rifampin: Rifampin lowered canagliflozin exposure, which may reduce the efficacy of INVOKAMET™. If an inducer of UGT enzymes must be coadministered with INVOKAMET™, consider increasing the dose to canagliflozin 150 mg twice daily if patients are currently tolerating INVOKAMET™ with 50 mg canagliflozin twice daily, have an eGFR ≥60 mL/min/1.73 m2, and require additional glycemic control.

    Digoxin
    Canagliflozin increased digoxin exposure. Digoxin, as a cationic drug, also has the potential to compete with metformin for common renal tubular transport systems. Monitor patients taking INVOKAMET™ with concomitant digoxin for a need to adjust dose of either drug.
  • Drug/Laboratory Test Interference

    Positive Urine Glucose Test
    Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors as SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose test results. Use alternative methods to monitor glycemic control.

    Interference With 1,5-Anhydroglucitol (1,5-AG) Assay
    Monitoring glycemic control with 1,5-AG assay is not recommended as measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors. Use alternative methods to monitor glycemic control.

USE IN SPECIFIC POPULATIONS

  • Pregnancy Category C: There are no adequate and well-controlled studies in pregnant women with INVOKAMET™ or its individual components. During pregnancy, consider appropriate alternative therapies, especially during the second and third trimesters.
  • Nursing Mothers: No studies in lactating animals have been conducted with the combined components of INVOKAMET™. Because of the potential for serious adverse reactions in nursing infants, discontinue INVOKAMET™.
  • Pediatric Use: Safety and effectiveness of INVOKAMET™ in patients <18 years of age have not been established.
  • Geriatric Use: Because renal function abnormalities can occur after initiating canagliflozin, metformin is substantially excreted by the kidney, and aging can be associated with reduced renal function, frequently monitor renal function after initiating INVOKAMET™ in elderly patients and adjust dose based on renal function.

    Canagliflozin
    2034 patients ≥65 years and 345 patients ≥75 years were exposed to canagliflozin in 9 clinical studies. Patients ≥65 years had a higher incidence of adverse reactions related to reduced intravascular volume (eg, hypotension, postural dizziness, orthostatic hypotension, syncope, and dehydration), particularly with the 300-mg dose, compared to younger patients; more prominent increase in the incidence was seen in patients who were ≥75 years. Smaller reductions in HbA1c relative to placebo were seen in patients ≥65 years (−0.61% with canagliflozin 100 mg and −0.74% with canagliflozin 300 mg) compared to younger patients (−0.72% with canagliflozin 100 mg and −0.87% with canagliflozin 300 mg).

    Metformin
    Controlled clinical studies of metformin did not include sufficient numbers of elderly patients to determine whether they respond differently from younger patients, although other reported clinical experience has not identified differences in responses between the elderly and younger patients. The initial and maintenance dosing of metformin should be conservative in patients with advanced age due to the potential for decreased renal function in this population. Any dose adjustment should be based on a careful assessment of renal function.
  • Renal Impairment: No dose adjustment of INVOKAMET™ is needed in patients with mild renal impairment or normal renal function (eGFR ≥60 mL/min/1.73 m2). INVOKAMET™ should not be used in patients with severe renal impairment (eGFR <30 mL/min/1.73 m2), with end-stage renal disease, or receiving dialysis.

OVERDOSAGE

  • In the event of an overdose with INVOKAMET™, contact the Poison Control Center. Employ the usual supportive measures (eg, remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring, and institute supportive treatment) as needed.

    Canagliflozin
    There were no reports of overdose during the clinical development program of canagliflozin.

    Metformin
    Overdose of metformin hydrochloride has occurred, including ingestion of amounts >50 grams. Hypoglycemia was reported in approximately 10% of cases, but no causal association with metformin hydrochloride has been established. Lactic acidosis has been reported in approximately 32% of metformin overdose cases.

ADVERSE REACTIONS

  • The most common (≥5%) adverse reactions with canagliflozin were female genital mycotic infections, urinary tract infections, and increased urination.
  • The most common adverse reactions due to initiation of metformin are diarrhea, nausea/vomiting, flatulence, asthenia, indigestion, abdominal discomfort, and headache.

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Plegridy™

(peginterferon beta-1a)

Indication

PLEGRIDY™ (peginterferon beta-1a) is indicated for the treatment of patients with relapsing forms of multiple sclerosis.

Important Safety Information

  • PLEGRIDY is contraindicated in patients with a history of hypersensitivity to natural or recombinant interferon beta or peginterferon, or any other component of the formulation.
  • Severe hepatic injury, including hepatitis, autoimmune hepatitis, and rare cases of severe hepatic failure, have been reported with interferon beta. Asymptomatic elevation of hepatic transaminases has also been reported, and in some patients has recurred upon rechallenge with interferon beta. Elevations in hepatic enzymes and hepatic injury have been observed with the use of PLEGRIDY in clinical studies. Monitor patients for signs and symptoms of hepatic injury.
  • Depression, suicidal ideation, and suicide occur more frequently in patients receiving interferon beta than in patients receiving placebo. Advise patients to report immediately any symptom of depression or suicidal ideation to their healthcare provider. If a patient develops depression or other severe psychiatric symptoms, consider stopping treatment with PLEGRIDY™ (peginterferon beta-1a).
  • Seizures are associated with the use of interferon beta. Exercise caution when administering PLEGRIDY to patients with a seizure disorder.
  • Anaphylaxis and other serious allergic reactions are rare complications of treatment with interferon beta. Discontinue PLEGRIDY if a serious allergic reaction occurs.
  • Injection site reactions, including injection site necrosis, can occur with the use of subcutaneous interferon beta. Decisions to discontinue therapy following necrosis at a single injection site should be based on the extent of the necrosis. For patients who continue therapy with PLEGRIDY™ (peginterferon beta-1a) after injection site necrosis has occurred, avoid administration of PLEGRIDY near the affected area until it is fully healed. If multiple lesions occur, discontinue PLEGRIDY until healing occurs.
  • Congestive heart failure, cardiomyopathy, and cardiomyopathy with congestive heart failure occur in patients receiving interferon beta. Monitor patients with significant cardiac disease for worsening of their cardiac condition during initiation and continuation of treatment with PLEGRIDY.
  • Interferon beta can cause decreased peripheral blood counts in all cell lines, including rare instances of pancytopenia and severe thrombocytopenia. Monitor patients for infections, bleeding, and symptoms of anemia. Monitor complete blood cell counts, differential white blood cell counts, and platelet counts during treatment with PLEGRIDY. Patients with myelosuppression may require more intensive monitoring of blood cell counts.
  • Autoimmune disorders of multiple target organs including idiopathic thrombocytopenia, hyper and hypothyroidism, and autoimmune hepatitis have been reported with interferon beta. If patients develop a new autoimmune disorder, consider stopping PLEGRIDY™ (peginterferon beta-1a).
  • The most common adverse reactions associated with PLEGRIDY treatment are injection site erythema, influenza-like illness, pyrexia, headache, myalgia, chills, injection site pain, asthenia, injection site pruritus, and arthralgia.
  • Advise patients that PLEGRIDY should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus.

Quillivant XR™

(methylphenidate HCl) for extended-release oral suspension, CII

INDICATION

Quillivant XR is a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). The efficacy of Quillivant XR was established in a 2-week, placebo-controlled trial in children aged 6 to 12 years with a diagnosis of ADHD. Accumulated efficacy data from other methylphenidate products were also considered.

IMPORTANT SAFETY INFORMATION

Warning: ABUSE AND DEPENDENCE

CNS stimulants, including Quillivant XR, other methylphenidate-containing products, and amphetamines, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy.

 

  Quillivant XR is contraindicated:
  ° In patients known to be hypersensitive to methylphenidate or other components of Quillivant XR. Hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported.
  ° During treatment with monoamine oxidase inhibitors (MAOIs), and also within 14 days following discontinuation of treatment with an MAOI because of the risk of hypertensive crisis.
  • Stroke and myocardial infarction have occurred in adults treated with CNS stimulants at recommended doses. Sudden death has occurred in children and adolescents with structural cardiac abnormalities and other serious cardiac problems, and in adults taking CNS stimulants at recommended doses for ADHD. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmias, coronary artery disease, or other serious cardiac problems. Further evaluate patients who develop exertional chest pain, unexplained syncope, or arrhythmias during treatment with Quillivant XR.
  • CNS stimulants cause an increase in blood pressure (mean increase approximately 2-4 mm Hg) and heart rate (mean increase approximately 3-6 bpm). Some individuals may have larger increases. Monitor all patients for hypertension and tachycardia.
  • Use of stimulants may cause psychotic or manic symptoms in patients with no prior history, or exacerbation of symptoms in patients with pre-existing psychiatric illness. Evaluate for bipolar disorder prior to Quillivant XR use.
  • Cases of painful and prolonged penile erections and priapism have been reported with methylphenidate products. Immediate medical attention should be sought if signs or symptoms of prolonged penile erections or priapism are observed.
  • Stimulants used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Careful observation for digital changes is necessary during treatment with ADHD stimulants.
  • CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. Growth should be monitored during treatment with stimulants, including Quillivant XR. Patients who are not growing or gaining weight as expected may need to have their treatment interrupted.
  • Based on accumulated data from other methylphenidate products, the most common (≥5% and twice the rate of placebo) adverse reactions are appetite decreased, insomnia, nausea, vomiting, dyspepsia, abdominal pain, weight decreased, anxiety, dizziness, irritability, affect lability, tachycardia, and blood pressure increased. There is limited experience with Quillivant XR in controlled trials. Based on this limited experience, the adverse reaction profile of Quillivant XR appears similar to other methylphenidate extended-release products. The most common (≥2% in the Quillivant XR group and greater than placebo) adverse reactions reported in the Phase 3 controlled study conducted in 45 ADHD patients (aged 6-12 years) were affect lability (9%), excoriation (4%), initial insomnia (2%), tic (2%), decreased appetite (2%), vomiting (2%), motion sickness (2%), eye pain (2%), and rash (2%).
  • Based on animal data, use of Quillivant XR during pregnancy may cause fetal harm. Quillivant XR should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
  • Nursing mothers should be advised to discontinue drug or discontinue nursing, taking into consideration the importance of the drug to the mother because methylphenidate is present in human milk.

 

Please see full Prescribing Information & Medication Guide, including BOXED WARNING regarding Abuse and Dependence.