Indication for Revonto (dantrolene sodium for injection)

Revonto is indicated, along with appropriate supportive measures, for the management of fulminant hypermetabolism of skeletal muscle characteristic of malignant hyperthermia crises in patients of all ages. It is also indicated preoperatively and sometimes postoperatively, to prevent or attenuate the development of clinical and laboratory signs of malignant hyperthermia in individuals judged to be malignant hyperthermia susceptible.

Important Safety Information for Revonto

The use of Revonto in the management of malignant hyperthermia crisis is not a substitute for previously known supportive measures. These measures must be individualized, but it will usually be necessary to discontinue the suspect triggering agents, attend to increased oxygen requirements, manage the metabolic acidosis, institute cooling when necessary, monitor urinary output, and monitor for electrolyte imbalance. Patients who receive i.v. dantrolene sodium preoperatively should have vital signs monitored.

If patients judged malignant hyperthermia susceptible are administered dantrolene sodium preoperatively, anesthetic preparation must still follow a standard malignant hyperthermia susceptible regimen, including the avoidance of known triggering agents. Monitoring for early clinical and metabolic signs of malignant hyperthermia is indicated because attenuation of malignant hyperthermia, rather than prevention, is possible.

Despite initial satisfactory response to i.v. dantrolene there have been reports of fatality, which involve patients who could not be weaned from dantrolene after initial treatment. The administration of i.v. dantrolene is associated with loss of grip strength and weakness in the legs, as well as drowsiness and dizziness. There have been reports of thrombophlebitis following administration of intravenous dantrolene. Tissue necrosis secondary to extravasation has been reported. Injection site reactions (pain, erythema, swelling), commonly due to extravasation, have been reported. Fatal and non-fatal liver disorders of an idiosyncratic or hypersensitivity type may occur with dantrolene sodium therapy.

For additional information visit www.revonto.com.

Click here for the Revonto full Prescribing Information

For More information on Malignant Hyperthermia please visit The Malignant Hyperthermia Association of the United States (MHAUS).


Indication for MYOBLOC (rimabotulinumtoxinB) injection

MYOBLOC is indicated for the treatment of adults with cervical dystonia to reduce the severity of abnormal head position and neck pain associated with cervical dystonia.

Important Safety Information for MYOBLOC

WARNING: DISTANT SPREAD OF TOXIN EFFECT

Postmarketing reports indicate that the effects of MYOBLOC and all botulinum toxin products may spread from the area of injection to produce symptoms consistent with botulinum toxin effects. These may include asthenia, generalized muscle weakness, diplopia, blurred vision, ptosis, dysphagia, dysphonia, dysarthria, urinary incontinence, and breathing difficulties. These symptoms have been reported hours to weeks after injection. Swallowing and breathing difficulties can be life threatening and there have been reports of death. The risk of symptoms is probably greatest in children treated for spasticity but symptoms can also occur in adults treated for spasticity and other conditions, particularly in those patients who have underlying conditions that would predispose them to these symptoms. In unapproved uses, including spasticity in children and adults, and in approved indications, cases of spread of effect have occurred at doses comparable to those used to treat cervical dystonia and at lower doses [see Warnings and Precautions].

MYOBLOC is contraindicated in patients with a known hypersensitivity to any botulinum toxin preparation or to any of the components in the formulation.

MYOBLOC is contraindicated for use in patients with infection at the proposed injection site(s).

The potency Units of MYOBLOC are specific to the preparation and assay method utilized. They are not interchangeable with other preparations of botulinum toxin products and, therefore, units of biological activity of MYOBLOC cannot be compared to or converted into units of any other botulinum toxin products assessed with any other specific assay method.

Treatment with MYOBLOC and other botulinum toxin products can result in swallowing or breathing difficulties. Patients with pre-existing swallowing or breathing difficulties may be more susceptible to these complications. In most cases, this is a consequence of weakening of muscles in the area of injection that are involved in breathing or swallowing. When distant effects occur, additional respiratory muscles may be involved.

Deaths as a complication of severe dysphagia have been reported after treatment with botulinum toxin. Dysphagia may persist for several months, and require use of a feeding tube to maintain adequate nutrition and hydration. Aspiration may result from severe dysphagia and is a particular risk when treating patients in whom swallowing or respiratory function is already compromised.

Treatment of cervical dystonia with botulinum toxins may weaken neck muscles that serve as accessory muscles of ventilation. This may result in a critical loss of breathing capacity in patients with respiratory disorders who may have become dependent upon these accessory muscles. There have been postmarketing reports of serious breathing difficulties, including respiratory failure, in cervical dystonia patients. Patients treated with botulinum toxin may require immediate medical attention should they develop problems with swallowing, speech or respiratory disorders. These reactions can occur within hours to weeks after injection with botulinum toxin.

Individuals with peripheral motor neuropathic diseases, amyotrophic lateral sclerosis, or neuromuscular junctional disorders (e.g., myasthenia gravis or Lambert-Eaton syndrome) should be monitored particularly closely when given botulinum toxin. Patients with neuromuscular disorders may be at increased risk of clinically significant effects including severe dysphagia and respiratory compromise from typical doses of MYOBLOC.

This product contains albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases. A theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD) also is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for albumin.

Only 9 subjects without a prior history of tolerating injections of type A botulinum toxin have been studied. Treatment of botulinum toxin na´ve patients should be initiated at lower doses of MYOBLOC.

Co-administration of MYOBLOC and aminoglycosides or other agents interfering with neuromuscular transmission (e.g., curare-like compounds) should only be performed with caution as the effect of the toxin may be potentiated.

The effect of administering different botulinum neurotoxin serotypes at the same time or within less than 4 months of each other is unknown. However, neuromuscular paralysis may be potentiated by co-administration or overlapping administration of different botulinum toxin serotypes.

It is not known whether MYOBLOC can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. MYOBLOC should be given to a pregnant woman only if clearly needed.

The most commonly reported adverse events associated with MYOBLOC treatment in all studies were dry mouth, dysphagia, dyspepsia, and injection site pain. Dry mouth and dysphagia were the adverse reactions most frequently resulting in discontinuation of treatment. There was an increased incidence of dysphagia with increased dose in the sternocleidomastoid muscle. The incidence of dry mouth showed some dose-related increase with doses injected into the splenius capitis, trapezius and sternocleidomastoid muscles.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Please see the full Prescribing Information, including Boxed WARNING and Medication Guide.


Important Safety Information for APOKYN (apomorphine hydrochloride injection)

APOKYN is indicated for the acute, intermittent treatment of hypnomobility, off episodes (end-of-dose wearing-off and unpredictable on-off episodes) associated with advanced Parkinson's disease. APOKYN has been studied as an adjunct to other medications.

Contraindications: APOKYN is contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients (notably sodium metabisulfite). Concomitant use of APOKYN with 5HT3 antagonists is contraindicated based on reports of profound hypotension and loss of consciousness when apomorphine was administered with ondansetron.

Nausea and Vomiting: At recommended doses of apomorphine, severe nausea and vomiting can be expected. Therefore, trimethobenzamide hydrochloride should be started 3 days prior to the initial dose of APOKYN and continued for at least 2 months. In clinical trials, 50% of patients (262/522) discontinued trimethobenzamide hydrochloride after 2 months of APOKYN.

Symptomatic Hypotension: Dopamine agonists, including APOKYN, can cause hypotension, orthostatic hypotension, and syncope. Alcohol, antihypertensive medications, and vasodilating medications may potentiate the hypotensive effect of apomorphine. These adverse events occurred with initial dosing and long-term treatment. Whether hypotension contributes to other significant events seen (eg, falls) is unknown.

SC Injection: APOKYN should be administered by subcutaneous injection, NOT intravenously, because serious adverse events may occur. Patients and caregivers must receive detailed instructions in the preparation and injection of doses, with particular attention paid to the correct use of the dosing pen.

Cardiac Events: QT Prolongation-Caution is recommended when administering APOKYN to patients with increased risk of QT prolongation, such as those with hypokalemia, hypomagnesemia, bradycardia, or a genetic predisposition, or who use other drugs that prolong the QT/QTc interval. Coronary Events-APOKYN reduces resting systolic and diastolic blood pressure and has the potential to exacerbate coronary (and cerebral) ischemia. Therefore, exercise caution when prescribing APOKYN for patients with known cardiovascular and cerebrovascular disease.

Intense Urges: Some people with PD have reported new or increased gambling urges, increased sexual urges, and other intense urges, while taking PD medicines, including APOKYN.

Potential for Abuse: There are reports of apomorphine abuse by patients with Parkinson's disease in other countries. These cases are characterized by increasingly frequent dosing leading to hallucinations, dyskinesia, and abnormal behavior.

Falls: Patients with Parkinson's disease (PD) are at risk of falling due to the underlying postural instability and concomitant autonomic instability seen in some patients with PD, and from syncope caused by the blood pressure lowering effects of the drugs used to treat PD. Subcutaneous apomorphine might increase the risk of falling by simultaneously lowering blood pressure and altering mobility.

Hallucinations / Psychotic-Like Behavior: Hallucinations were reported in some patients during clinical development. Post marketing reports indicate that patients may experience new or worsening mental status and behavioral changes, which may be severe, including psychotic-like behavior after starting or increasing the dose of APOKYN. Other drugs prescribed to improve the symptoms of Parkinson's disease can have similar effects on thinking and behavior. This abnormal thinking and behavior can consist of one or more of a variety of manifestations, including paranoid ideation, delusions, hallucinations, confusion, disorientation, aggressive behavior, agitation, and delirium.

Patients with a major psychotic disorder should ordinarily not be treated with APOKYN because of the risk of exacerbating psychosis. In addition, certain medications used to treat psychosis may exacerbate the symptoms of Parkinson's disease and may decrease the effectiveness of APOKYN.

Falling Asleep During Activities of Daily Living (ADL): There have been literature reports of patients treated with apomorphine subcutaneous injections who suddenly fell asleep while engaged in ADL. Patients should be advised not to drive or participate in potentially dangerous activities until it is known how APOKYN affects them. Patients should be continually reassessed for daytime drowsiness or sleepiness.

Adverse Events: Injection-site reactions, including bruising, granuloma, and pruritus, have been reported. The most common adverse events seen in controlled trials were yawning, dyskinesias, nausea and/or vomiting, somnolence, dizziness, rhinorrhea, hallucinations, edema, chest pain, and increased sweating, flushing, and pallor.

Melanoma: Epidemiological studies have shown that patients with Parkinson's disease have a higher risk (2- to approximately 6-fold higher) of developing melanoma than the general population. Whether the increased risk observed was due to Parkinson's disease or other factors, such as drugs used to treat Parkinson's disease, is unclear. For the reasons stated above, patients and providers are advised to monitor for melanomas frequently and on a regular basis when using APOKYN for any indication. Periodic skin examinations should be performed by appropriately qualified individuals (eg, dermatologists).

To report SUSPECTED ADVERSE REACTIONS or product complaints, contact US WorldMeds at 1-877-727-6596 (877- 7APOKYN). You may also report SUSPECTED ADVERSE REACTIONS to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full Prescribing Information.

All trademarks are the property of their respective owners.

For more information on APOKYN, please visit www.apokyn.com