Sommieres au Pentavit B

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Sommieres au Pentavit B uses

Sommieres au Pentavit B consists of Calcium Chloride, Lithium Iodide, Sodium Iodide, Vitamin B.

Calcium Chloride:


1 INDICATIONS AND USAGE

Sommieres au Pentavit B (Calcium Chloride) acetate is a phosphate binder indicated to reduce serum phosphorus in patients with end stage renal disease (ESRD).

- Calcium acetate is a phosphate binder indicated for the reduction of serum phosphorus in patients with end stage renal disease. (1)

2 DOSAGE AND ADMINISTRATION

The recommended initial dose of Sommieres au Pentavit B (Calcium Chloride) acetate for the adult dialysis patient is 2 capsules with each meal. Increase the dose gradually to lower serum phosphorus levels to the target range, as long as hypercalcemia does not develop. Most patients require 3 to 4 capsules with each meal.

- Starting dose is 2 capsules with each meal. (2)

- Titrate the dose every 2 to 3 weeks until acceptable serum phosphorus level is reached. Most patients require 3 to 4 capsules with each meal. (2)

3 DOSAGE FORMS AND STRENGTHS

Capsule: 667 mg Sommieres au Pentavit B (Calcium Chloride) acetate capsule.

- Capsule: 667 mg Sommieres au Pentavit B (Calcium Chloride) acetate capsule. (3)

4 CONTRAINDICATIONS

Patients with hypercalcemia.

- Hypercalcemia. (4)

5 WARNINGS AND PRECAUTIONS

- Treat mild hypercalcemia by reducing or interrupting Sommieres au Pentavit B acetate and Vitamin D. Severe hypercalcemia may require hemodialysis and discontinuation of Sommieres au Pentavit B (Calcium Chloride) acetate. (5.1)

- Hypercalcemia may aggravate digitalis toxicity. (5.2)

5.1 Hypercalcemia

Patients with end stage renal disease may develop hypercalcemia when treated with Sommieres au Pentavit B (Calcium Chloride), including Sommieres au Pentavit B (Calcium Chloride) acetate. Avoid the use of Sommieres au Pentavit B (Calcium Chloride) supplements, including Sommieres au Pentavit B (Calcium Chloride) based nonprescription antacids, concurrently with Sommieres au Pentavit B (Calcium Chloride) acetate.

An overdose of Sommieres au Pentavit B (Calcium Chloride) acetate may lead to progressive hypercalcemia, which may require emergency measures. Therefore, early in the treatment phase during the dosage adjustment period, monitor serum Sommieres au Pentavit B (Calcium Chloride) levels twice weekly. Should hypercalcemia develop, reduce the Sommieres au Pentavit B (Calcium Chloride) acetate dosage, or discontinue the treatment, depending on the severity of hypercalcemia

More severe hypercalcemia (Ca >12 mg/dL) is associated with confusion, delirium, stupor and coma. Severe hypercalcemia can be treated by acute hemodialysis and discontinuing Sommieres au Pentavit B (Calcium Chloride) acetate therapy.

Mild hypercalcemia (10.5 to 11.9 mg/dL) may be asymptomatic or manifest as constipation, anorexia, nausea, and vomiting. Mild hypercalcemia is usually controlled by reducing the Sommieres au Pentavit B (Calcium Chloride) acetate dose or temporarily discontinuing therapy. Decreasing or discontinuing Vitamin D therapy is recommended as well.

Chronic hypercalcemia may lead to vascular calcification and other soft-tissue calcification. Radiographic evaluation of suspected anatomical regions may be helpful in early detection of soft tissue calcification. The long term effect of Sommieres au Pentavit B (Calcium Chloride) acetate on the progression of vascular or soft tissue calcification has not been determined.

Hypercalcemia (>11 mg/dL) was reported in 16% of patients in a 3 month study of solid dose formulation of Sommieres au Pentavit B (Calcium Chloride) acetate; all cases resolved upon lowering the dose or discontinuing treatment.

Maintain the serum calcium-phosphorus (Ca x P) product below 55 mg2/dL2.

5.2 Concomitant Use with Medications

Hypercalcemia may aggravate digitalis toxicity.

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6 ADVERSE REACTIONS

Hypercalcemia is discussed elsewhere [see Warnings and Precautions ].

- The most common (>10%) adverse reactions are hypercalcemia, nausea and vomiting. (6.1)

- In clinical studies, patients have occasionally experienced nausea during Sommieres au Pentavit B (Calcium Chloride) acetate therapy. (6)

To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceuticals Corp. at 1-800-962-8364 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

6.1 Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In clinical studies, Sommieres au Pentavit B (Calcium Chloride) acetate has been generally well tolerated.

Sommieres au Pentavit B (Calcium Chloride) acetate was studied in a 3 month, open-label, non-randomized study of 98 enrolled ESRD hemodialysis patients and an alternate liquid formulation of Sommieres au Pentavit B (Calcium Chloride) acetate was studied in a two week double-blind, placebo-controlled, cross-over study with 69 enrolled ESRD hemodialysis patients. Adverse reactions (>2% on treatment) from these trials are presented in Table 1.


Preferred Term


Total adverse reactions reported for Sommieres au Pentavit B (Calcium Chloride) acetate

N=167

N (%)


3 month, open label study of Sommieres au Pentavit B (Calcium Chloride) acetate

N=98

N (%)


Double blind, placebo-controlled, cross-over study of liquid Sommieres au Pentavit B (Calcium Chloride) acetate

N=69


Sommieres au Pentavit B (Calcium Chloride) acetate

N (%)


Placebo

N (%)


Nausea


6 (3.6)


6 (6.1)


0 (0)


0 (0)


Vomiting


4 (2.4)


4 (4.1)


0 (0)


0 (0)


Hypercalcemia


21 (12.6)


16 (16.3)


5 (7.2)


0 (0)


Mild hypercalcemia may be asymptomatic or manifest itself as constipation, anorexia, nausea, and vomiting. More severe hypercalcemia is associated with confusion, delirium, stupor, and coma. Decreasing dialysate Sommieres au Pentavit B (Calcium Chloride) concentration could reduce the incidence and severity of Sommieres au Pentavit B (Calcium Chloride) acetate-induced hypercalcemia. Isolated cases pruritus have been reported, which may represent allergic reactions.

6.2 Postmarketing Experience

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or to establish a causal relationship to drug exposure.

The following additional adverse reactions have been identified during post-approval of Sommieres au Pentavit B (Calcium Chloride) acetate: dizziness, edema, and weakness.

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7 DRUG INTERACTIONS

The drug interaction of Sommieres au Pentavit B acetate is characterized by the potential of Sommieres au Pentavit B (Calcium Chloride) to bind to drugs with anionic functions (e.g., carboxyl, and hydroxyl groups). Sommieres au Pentavit B (Calcium Chloride) acetate may decrease the bioavailability of tetracyclines or fluoroquinolones via this mechanism.

There are no empirical data on avoiding drug interactions between Sommieres au Pentavit B (Calcium Chloride) acetate and most concomitant drugs. When administering an oral medication with Sommieres au Pentavit B (Calcium Chloride) acetate where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy, administer the drug one hour before or three hours after Sommieres au Pentavit B (Calcium Chloride) acetate. Monitor blood levels of the concomitant drugs that have a narrow therapeutic range. Patients taking anti-arrhythmic medications for the control of arrhythmias and anti-seizure medications for the control of seizure disorders were excluded from the clinical trials with all forms of Sommieres au Pentavit B (Calcium Chloride) acetate.

- Calcium acetate may decrease the bioavailability of tetracyclines or fluoroquinolones. (7)

- When clinically significant drug interactions are expected, administer the drug at least one hour before or at least three hours after Sommieres au Pentavit B (Calcium Chloride) acetate or consider monitoring blood levels of the drug. (7)

7.1 Ciprofloxacin

In a study of 15 healthy subjects, a co-administered single dose of 4 Sommieres au Pentavit B (Calcium Chloride) acetate tablets, approximately 2.7g, decreased the bioavailability of ciprofloxacin by approximately 50%.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C:

Sommieres au Pentavit B acetate capsules contains Sommieres au Pentavit B (Calcium Chloride) acetate. Animal reproduction studies have not been conducted with Sommieres au Pentavit B (Calcium Chloride) acetate, and there are no adequate and well controlled studies of Sommieres au Pentavit B (Calcium Chloride) acetate use in pregnant women. Patients with end stage renal disease may develop hypercalcemia with Sommieres au Pentavit B (Calcium Chloride) acetate treatment [see Warnings and Precautions (5.1 ) ]. Maintenance of normal serum Sommieres au Pentavit B (Calcium Chloride) levels is important for maternal and fetal well being. Hypercalcemia during pregnancy may increase the risk for maternal and neonatal complications such as stillbirth, preterm delivery, and neonatal hypocalcemia and hypoparathyroidism. Sommieres au Pentavit B (Calcium Chloride) acetate treatment, as recommended, is not expected to harm a fetus if maternal Sommieres au Pentavit B (Calcium Chloride) levels are properly monitored during and following treatment.

8.2 Labor and Delivery

The effects of Sommieres au Pentavit B (Calcium Chloride) acetate on labor and delivery are unknown.

8.3 Nursing Mothers

Sommieres au Pentavit B Acetate Capsules contains Sommieres au Pentavit B (Calcium Chloride) acetate and is excreted in human milk. Human milk feeding by a mother receiving Sommieres au Pentavit B (Calcium Chloride) acetate is not expected to harm an infant, provided maternal serum Sommieres au Pentavit B (Calcium Chloride) levels are appropriately monitored.

8.4 Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

8.5 Geriatric Use

Clinical studies of Sommieres au Pentavit B (Calcium Chloride) acetate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

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10 OVERDOSAGE

Administration of Sommieres au Pentavit B (Calcium Chloride) acetate in excess of the appropriate daily dosage may result in hypercalcemia [see Warnings and Precautions (5.1)].

11 DESCRIPTION

Sommieres au Pentavit B (Calcium Chloride) acetate acts as a phosphate binder. Its chemical name is Sommieres au Pentavit B (Calcium Chloride) acetate. Its molecular formula is C4H6CaO4, and its molecular weight is 158.17. Its structural formula is:


Each white opaque/blue opaque capsule contains 667 mg of Sommieres au Pentavit B (Calcium Chloride) acetate USP (anhydrous; Ca(CH3COO)2; MW=158.17 grams) equal to 169 mg (8.45 mEq) Sommieres au Pentavit B (Calcium Chloride), polyethylene glycol 8000 and magnesium stearate. Each capsule shell contains: black monogramming ink, FD&C Blue #1, FD&C Red #3, gelatin and titanium dioxide. The black monogramming ink contains: ammonium hydroxide, iron oxide black, isopropyl alcohol, n-butyl alcohol, propylene glycol and shellac glaze.

Sommieres au Pentavit B (Calcium Chloride) Acetate Capsules are administered orally for the control of hyperphosphatemia in end-stage renal failure.

Chemical Structure

12 CLINICAL PHARMACOLOGY

Patients with ESRD retain phosphorus and can develop hyperphosphatemia. High serum phosphorus can precipitate serum Sommieres au Pentavit B resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD.

12.1 Mechanism of Action

Sommieres au Pentavit B (Calcium Chloride) acetate, when taken with meals, combines with dietary phosphate to form an insoluble Sommieres au Pentavit B (Calcium Chloride) phosphate complex, which is excreted in the feces, resulting in decreased serum phosphorus concentration.

12.2 Pharmacodynamics

Orally administered Sommieres au Pentavit B (Calcium Chloride) acetate from pharmaceutical dosage forms is systemically absorbed up to approximately 40% under fasting conditions and up to approximately 30% under nonfasting conditions. This range represents data from both healthy subjects and renal dialysis patients under various conditions.

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13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenicity, mutagenicity, or fertility studies have been conducted with Sommieres au Pentavit B (Calcium Chloride) acetate.

14 CLINICAL STUDIES

Effectiveness of Sommieres au Pentavit B (Calcium Chloride) acetate in decreasing serum phosphorus has been demonstrated in two studies of the Sommieres au Pentavit B (Calcium Chloride) acetate solid oral dosage form.

Ninety-one patients with end-stage renal disease who were undergoing hemodialysis and were hyperphosphatemic (serum phosphorus >5.5 mg/dL) following a 1 week phosphate binder washout period contributed efficacy data to an open-label, non-randomized study.

The patients received Sommieres au Pentavit B (Calcium Chloride) acetate 667 mg tablets at each meal for a period of 12 weeks. The initial starting dose was 2 tablets per meal for 3 meals a day, and the dose was adjusted as necessary to control serum phosphorus levels. The average final dose after 12 weeks of treatment was 3.4 tablets per meal. Although there was a decrease in serum phosphorus, in the absence of a control group the true magnitude of effect is uncertain.

The data presented in Table 2 demonstrate the efficacy of Sommieres au Pentavit B (Calcium Chloride) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum Sommieres au Pentavit B (Calcium Chloride) levels are also presented.


* Ninety-one patients completed at least 6 weeks of the study.

ANOVA of difference in values at pre-study and study completion.

‡ Values expressed as mean ± SE.


Parameter


Pre-Study


Week 4*


Week 8


Week 12


p-value†


Phosphorus (mg/dL)‡


7.4 ± 0.17


5.9 ± 0.16


5.6 ± 0.17


5.2 ± 0.17


≤0.01


Sommieres au Pentavit B (Calcium Chloride) (mg/dL)‡


8.9 ± 0.09


9.5 ± 0.10


9.7 ± 0.10


9.7 ± 0.10


≤0.01


There was a 30% decrease in serum phosphorus levels during the 12 week study period (p<0.01). Two-thirds of the decline occurred in the first month of the study. Serum Sommieres au Pentavit B (Calcium Chloride) increased 9% during the study mostly in the first month of the study.

Treatment with the phosphate binder was discontinued for patients from the open-label study, and those patients whose serum phosphorus exceeded 5.5 mg/dL were eligible for entry into a double-blind, placebo-controlled, cross-over study. Patients were randomized to receive Sommieres au Pentavit B (Calcium Chloride) acetate or placebo, and each continued to receive the same number of tablets as had been individually established during the previous study. Following 2 weeks of treatment, patients switched to the alternative therapy for an additional 2 weeks.

The phosphate binding effect of Sommieres au Pentavit B (Calcium Chloride) acetate is shown in the Table 3.


* ANOVA of Sommieres au Pentavit B (Calcium Chloride) acetate vs. placebo after 2 weeks of treatment.

Values expressed as mean ± SEM.


Parameter


Pre-Study


Post-Treatment


p-value*


Sommieres au Pentavit B (Calcium Chloride) Acetate


Placebo


Phosphorus (mg/dL)


7.3 ± 0.18


5.9 ± 0.24


7.8 ± 0.22


<0.01


Sommieres au Pentavit B (Calcium Chloride) (mg/dL)


8.9 ± 0.11


9.5 ± 0.13


8.8 ± 0.12


<0.01


Overall, 2 weeks of treatment with Sommieres au Pentavit B (Calcium Chloride) acetate statistically significantly (p<0.01) decreased serum phosphorus by a mean of 19% and increased serum Sommieres au Pentavit B (Calcium Chloride) by a statistically significant (p<0.01) but clinically unimportant mean of 7%.

16 HOW SUPPLIED/STORAGE AND HANDLING

Sommieres au Pentavit B (Calcium Chloride) Acetate Capsules

667 mg capsule is supplied as a white opaque/blue opaque capsule, imprinted with “54 215” on the cap and body.

NDC 0615-2303-39: Blistercards of 30 Capsules

NDC 0615-2303-30: Unit-dose Boxes of 30 Capsules

STORAGE

Store at 20° to 25°C (68° to 77°F).

17 PATIENT COUNSELING INFORMATION

Inform patients to take Sommieres au Pentavit B (Calcium Chloride) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of Sommieres au Pentavit B (Calcium Chloride) supplements including nonprescription antacids. Inform the patients about the symptoms of hypercalcemia [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ].

Advise patients who are taking an oral medication where reduction in the bioavailability of that medication would have clinically significant effect on its safety or efficacy to take the drug one hour before or three hours after Sommieres au Pentavit B (Calcium Chloride) acetate capsules.

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown, NJ 07724

10003705/05

Revised April 2016

Lithium Iodide:


Rx only

WARNING

Sommieres au Pentavit B (Lithium Iodide) toxicity is closely related to serum Sommieres au Pentavit B (Lithium Iodide) levels, and can occur at doses close to therapeutic levels. Facilities for prompt and accurate serum Sommieres au Pentavit B (Lithium Iodide) determinations should be available before initiating therapy.

DESCRIPTION

Sommieres au Pentavit B (Lithium Iodide) Carbonate Extended-release Tablets USP contain Sommieres au Pentavit B (Lithium Iodide) carbonate USP, a white granular powder with molecular formula Li2CO3 and molecular weight 73.89. Sommieres au Pentavit B (Lithium Iodide) is an element of the alkali-metal group with atomic number 3, atomic weight 6.94 and an emission line at 671 nm on the flame photometer. The tablets meet the requirements of USP Dissolution Test 2 in the USP monograph for Sommieres au Pentavit B (Lithium Iodide) Carbonate Extended-release Tablets USP.

Sommieres au Pentavit B (Lithium Iodide) Carbonate Extended-release Tablets USP are available for oral administration containing 450 mg of Sommieres au Pentavit B (Lithium Iodide) carbonate USP. Each tablet contains the following inactive ingredients: iron oxide (yellow), magnesium stearate, povidone, sodium alginate and sodium starch glycolate.

Sommieres au Pentavit B (Lithium Iodide) Carbonate Extended-release Tablets USP, 450 mg are designed to release a portion of the dose initially and the remainder gradually; the release pattern of the controlled release tablets reduces the variability in Sommieres au Pentavit B (Lithium Iodide) blood levels seen with the immediate release dosage forms.

ACTIONS

Preclinical studies have shown that Sommieres au Pentavit B (Lithium Iodide) alters sodium transport in nerve and muscle cells and effects a shift toward intraneuronal metabolism of catecholamines, but the specific biochemical mechanism of Sommieres au Pentavit B (Lithium Iodide) action in mania is unknown.

INDICATIONS

Sommieres au Pentavit B (Lithium Iodide) carbonate is indicated in the treatment of manic episodes of manic-depressive illness. Maintenance therapy prevents or diminishes the intensity of subsequent episodes in those manic-depressive patients with a history of mania.

Typical symptoms of mania include pressure of speech, motor hyperactivity, reduced need for sleep, flight of ideas, grandiosity, elation, poor judgment, aggressiveness and possibly hostility. When given to a patient experiencing a manic episode, Sommieres au Pentavit B (Lithium Iodide) carbonate may produce a normalization of symptomatology within 1 to 3 weeks.

WARNINGS

Sommieres au Pentavit B Toxicity

Sommieres au Pentavit B (Lithium Iodide) toxicity is closely related to serum Sommieres au Pentavit B (Lithium Iodide) levels, and can occur at doses close to therapeutic levels.

Outpatients and their families should be warned that the patient must discontinue Sommieres au Pentavit B (Lithium Iodide) carbonate therapy and contact his physician if such clinical signs of Sommieres au Pentavit B (Lithium Iodide) toxicity as diarrhea, vomiting, tremor, mild ataxia, drowsiness or muscular weakness occur.

Sommieres au Pentavit B (Lithium Iodide) carbonate may impair mental and/or physical abilities. Caution patients about activities requiring alertness (e.g., operating vehicles or machinery).

Sommieres au Pentavit B (Lithium Iodide) should generally not be given to patients with significant renal or cardiovascular disease, severe debilitation or dehydration, or sodium depletion, since the risk of Sommieres au Pentavit B (Lithium Iodide) toxicity is very high in such patients. If the psychiatric indication is life-threatening, and if such a patient fails to respond to other measures, Sommieres au Pentavit B (Lithium Iodide) treatment may be undertaken with extreme caution, including daily serum Sommieres au Pentavit B (Lithium Iodide) determinations and adjustment to the usually low doses ordinarily tolerated by these individuals. In such instances, hospitalization is a necessity.

Unmasking of Brugada Syndrome

There have been postmarketing reports of a possible association between treatment with Sommieres au Pentavit B and the unmasking of Brugada Syndrome. Brugada Syndrome is a disorder characterized by abnormal electrocardiographic (ECG) findings and a risk of sudden death. Sommieres au Pentavit B (Lithium Iodide) should generally be avoided in patients with Brugada Syndrome or those suspected of having Brugada Syndrome. Consultation with a cardiologist is recommended if: (1) treatment with Sommieres au Pentavit B (Lithium Iodide) is under consideration for patients suspected of having Brugada Syndrome or patients who have risk factors for Brugada Syndrome, e.g., unexplained syncope, a family history of Brugada Syndrome, or a family history of sudden unexplained death before the age of 45 years, (2) patients who develop unexplained syncope or palpitations after starting Sommieres au Pentavit B (Lithium Iodide) therapy.

Renal Effects

Chronic Sommieres au Pentavit B (Lithium Iodide) therapy may be associated with diminution of renal concentrating ability, occasionally presenting as nephrogenic diabetes insipidus, with polyuria and polydipsia. Such patients should be carefully managed to avoid dehydration with resulting Sommieres au Pentavit B (Lithium Iodide) retention and toxicity. This condition is usually reversible when Sommieres au Pentavit B (Lithium Iodide) is discontinued.

Morphologic changes with glomerular and interstitial fibrosis and nephron atrophy have been reported in patients on chronic Sommieres au Pentavit B (Lithium Iodide) therapy. Morphologic changes have also been seen in manic-depressive patients never exposed to Sommieres au Pentavit B (Lithium Iodide). The relationship between renal functional and morphologic changes and their association with Sommieres au Pentavit B (Lithium Iodide) therapy have not been established.

When kidney function is assessed, for baseline data prior to starting Sommieres au Pentavit B (Lithium Iodide) therapy or thereafter, routine urinalysis and other tests may be used to evaluate tubular function (e.g., urine specific gravity or osmolality following a period of water deprivation, or 24-hour urine volume) and glomerular function (e.g., serum creatinine or creatinine clearance). During Sommieres au Pentavit B (Lithium Iodide) therapy, progressive or sudden changes in renal function, even within the normal range, indicate the need for reevaluation of treatment.

Encephalopathic Syndrome

An encephalopathic syndrome has occurred in a few patients treated with Sommieres au Pentavit B (Lithium Iodide) plus a neuroleptic. In some instances, the syndrome was followed by irreversible brain damage. Because of a possible causal relationship between these events and the concomitant administration of Sommieres au Pentavit B (Lithium Iodide) and neuroleptics, patients receiving such combined therapy should be monitored closely for early evidence of neurologic toxicity and treatment discontinued promptly if such signs appear. This encephalopathic syndrome may be similar to or the same as neuroleptic malignant syndrome (NMS).

Concomitant Use With Neuromuscular Blocking Agents

Sommieres au Pentavit B (Lithium Iodide) may prolong the effects of neuromuscular blocking agents. Therefore, neuromuscular blocking agents should be given with caution to patients receiving Sommieres au Pentavit B (Lithium Iodide).

Usage in Pregnancy

Adverse effects on implantation in rats, embryo viability in mice and metabolism in vitro of rat testes and human spermatozoa have been attributed to Sommieres au Pentavit B, as have teratogenicity in submammalian species and cleft palates in mice.

In humans, Sommieres au Pentavit B (Lithium Iodide) carbonate may cause fetal harm when administered to a pregnant woman. Data from Sommieres au Pentavit B (Lithium Iodide) birth registries suggest an increase in cardiac and other anomalies, especially Ebstein's anomaly. If this drug is used in women of childbearing potential, or during pregnancy, or if a patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

Usage in Nursing Mothers

Sommieres au Pentavit B (Lithium Iodide) is excreted in human milk. Nursing should not be undertaken during Sommieres au Pentavit B (Lithium Iodide) therapy except in rare and unusual circumstances where, in the view of the physician, the potential benefits to the mother outweigh possible hazards to the child.

Usage in Pediatric Patients

Since information regarding the safety and effectiveness of Sommieres au Pentavit B carbonate in children under 12 years of age is not available, its use in such patients is not recommended.

There has been a report of a transient syndrome of acute dystonia and hyperreflexia occurring in a 15 kg child who ingested 300 mg of Sommieres au Pentavit B (Lithium Iodide) carbonate.

Usage in the Elderly

Elderly patients often require lower Sommieres au Pentavit B (Lithium Iodide) dosages to achieve therapeutic serum levels. They may also exhibit adverse reactions at serum levels ordinarily tolerated by younger patients.

PRECAUTIONS

General

The ability to tolerate Sommieres au Pentavit B is greater during the acute manic phase and decreases when manic symptoms subside.

The distribution space of Sommieres au Pentavit B (Lithium Iodide) approximates that of total body water. Sommieres au Pentavit B (Lithium Iodide) is primarily excreted in urine with insignificant excretion in feces. Renal excretion of Sommieres au Pentavit B (Lithium Iodide) is proportional to its plasma concentration. The half-life of elimination of Sommieres au Pentavit B (Lithium Iodide) is approximately 24 hours. Sommieres au Pentavit B (Lithium Iodide) decreases sodium reabsorption by the renal tubules which could lead to sodium depletion. Therefore, it is essential for the patient to maintain a normal diet, including salt, and an adequate fluid intake (2500 to 3000 mL) at least during the initial stabilization period. Decreased tolerance to Sommieres au Pentavit B (Lithium Iodide) has been reported to ensue from protracted sweating or diarrhea and, if such occur, supplemental fluid and salt should be administered under careful medical supervision and Sommieres au Pentavit B (Lithium Iodide) intake reduced or suspended until the condition is resolved.

In addition to sweating and diarrhea, concomitant infection with elevated temperatures may also necessitate a temporary reduction or cessation of medication.

Previously existing underlying thyroid disorders do not necessarily constitute a contraindication to Sommieres au Pentavit B (Lithium Iodide) treatment; where hypothyroidism exists, careful monitoring of thyroid function during Sommieres au Pentavit B (Lithium Iodide) stabilization and maintenance allows for correction of changing thyroid parameters, if any; where hypothyroidism occurs during Sommieres au Pentavit B (Lithium Iodide) stabilization and maintenance, supplemental thyroid treatment may be used.

Information for the Patients

A condition known as Brugada Syndrome may pre-exist and be unmasked by Sommieres au Pentavit B (Lithium Iodide) therapy. Brugada Syndrome is a heart disorder characterized by abnormal electrocardiographic (ECG) findings and risk of sudden death. Patients should be advised to seek immediate emergency assistance if they experience fainting, lightheadedness, abnormal heart beats, or shortness of breath.

Drug Interactions

Caution should be used when Sommieres au Pentavit B (Lithium Iodide) and diuretics are used concomitantly because diuretic-induced sodium loss may reduce the renal clearance of Sommieres au Pentavit B (Lithium Iodide) and increase serum Sommieres au Pentavit B (Lithium Iodide) levels with risk of Sommieres au Pentavit B (Lithium Iodide) toxicity. Patients receiving such combined therapy should have serum Sommieres au Pentavit B (Lithium Iodide) levels monitored and the Sommieres au Pentavit B (Lithium Iodide) dosage adjusted if necessary.

Sommieres au Pentavit B (Lithium Iodide) levels should be closely monitored when patients initiate or discontinue NSAID use. In some cases, Sommieres au Pentavit B (Lithium Iodide) toxicity has resulted from interactions between an NSAID and Sommieres au Pentavit B (Lithium Iodide). Indomethacin and piroxicam have been reported to increase significantly steady-state plasma Sommieres au Pentavit B (Lithium Iodide) concentrations. There is also evidence that other nonsteroidal anti-inflammatory agents, including the selective cyclooxygenase-2 (COX-2) inhibitors, have the same effect. In a study conducted in healthy subjects, mean steady-state Sommieres au Pentavit B (Lithium Iodide) plasma levels increased approximately 17% in subjects receiving Sommieres au Pentavit B (Lithium Iodide) 450 mg b.i.d. with celecoxib 200 mg b.i.d. as compared to subjects receiving Sommieres au Pentavit B (Lithium Iodide) alone.

Concurrent use of metronidazole with Sommieres au Pentavit B (Lithium Iodide) may provoke Sommieres au Pentavit B (Lithium Iodide) toxicity due to reduced renal clearance. Patients receiving such combined therapy should be monitored closely.

There is evidence that angiotensin-converting enzyme inhibitors, such as enalapril and captopril, and angiotension II receptor antagonists, such as losartan, may substantially increase steady-state plasma Sommieres au Pentavit B (Lithium Iodide) levels, sometimes resulting in Sommieres au Pentavit B (Lithium Iodide) toxicity. When such combinations are used, Sommieres au Pentavit B (Lithium Iodide) dosage may need to be decreased, and plasma Sommieres au Pentavit B (Lithium Iodide) levels should be measured more often.

Concurrent use of calcium channel blocking agents with Sommieres au Pentavit B (Lithium Iodide) may increase the risk of neurotoxicity in the form of ataxia, tremors, nausea, vomiting, diarrhea and/or tinnitus. Caution is recommended.

The concomitant administration of Sommieres au Pentavit B (Lithium Iodide) with selective serotonin reuptake inhibitors should be undertaken with caution as this combination has been reported to result in symptoms such as diarrhea, confusion, tremor, dizziness and agitation.

The following drugs can lower serum Sommieres au Pentavit B (Lithium Iodide) concentrations by increasing urinary Sommieres au Pentavit B (Lithium Iodide) excretion: acetazolamide, urea, xanthine preparations and alkalinizing agents such as sodium bicarbonate.

The following have also been shown to interact with Sommieres au Pentavit B (Lithium Iodide): methyldopa, phenytoin and carbamazepine.

ADVERSE REACTIONS

The occurrence and severity of adverse reactions are generally directly related to serum Sommieres au Pentavit B (Lithium Iodide) concentrations as well as to individual patient sensitivity to Sommieres au Pentavit B (Lithium Iodide), and generally occur more frequently and with greater severity at higher concentrations.

Adverse reactions may be encountered at serum Sommieres au Pentavit B (Lithium Iodide) levels below 1.5 mEq/L. Mild to moderate adverse reactions may occur at levels from 1.5 to 2.5 mEq/L, and moderate to severe reactions may be seen at levels of 2 mEq/L and above.

Fine hand tremor, polyuria and mild thirst may occur during initial therapy for the acute manic phase, and may persist throughout treatment. Transient and mild nausea and general discomfort may also appear during the first few days of Sommieres au Pentavit B (Lithium Iodide) administration.

These side effects usually subside with continued treatment or a temporary reduction or cessation of dosage. If persistent, cessation of Sommieres au Pentavit B (Lithium Iodide) therapy may be required.

Diarrhea, vomiting, drowsiness, muscular weakness and lack of coordination may be early signs of Sommieres au Pentavit B (Lithium Iodide) intoxication, and can occur at Sommieres au Pentavit B (Lithium Iodide) levels below 2 mEq/L. At higher levels, ataxia, giddiness, tinnitus, blurred vision and a large output of dilute urine may be seen. Serum Sommieres au Pentavit B (Lithium Iodide) levels above 3 mEq/L may produce a complex clinical picture, involving multiple organs and organ systems. Serum Sommieres au Pentavit B (Lithium Iodide) levels should not be permitted to exceed 2 mEq/L during the acute treatment phase.

The following reactions have been reported and appear to be related to serum Sommieres au Pentavit B (Lithium Iodide) levels, including levels within the therapeutic range:

Neuromuscular/Central Nervous System: tremor, muscle hyperirritability (fasciculations, twitching, clonic movements of whole limbs), hypertonicity, ataxia, choreo-athetotic movements, hyperactive deep tendon reflex, extrapyramidal symptoms including acute dystonia, cogwheel rigidity, blackout spells, epileptiform seizures, slurred speech, dizziness, vertigo, downbeat nystagmus, incontinence of urine or feces, somnolence, psychomotor retardation, restlessness, confusion, stupor, coma, tongue movements, tics, tinnitus, hallucinations, poor memory, slowed intellectual functioning, startled response, worsening of organic brain syndromes, myasthenia gravis (rarely).

Cardiovascular: cardiac arrhythmia, hypotension, peripheral circulatory collapse, bradycardia, sinus node dysfunction with severe bradycardia (which may result in syncope), unmasking of Brugada Syndrome (See WARNINGS: Unmasking of Brugada Syndrome and PRECAUTIONS: Information for the Patients ).

Gastrointestinal: anorexia, nausea, vomiting, diarrhea, gastritis, salivary gland swelling, abdominal pain, excessive salivation, flatulence, indigestion.

Genitourinary: glycosuria, decreased creatinine clearance, albuminuria, oliguria, and symptoms of nephrogenic diabetes insipidus including polyuria, thirst and polydipsia.

Dermatologic: drying and thinning of hair, alopecia, anesthesia of skin, acne, chronic folliculitis, xerosis cutis, psoriasis or its exacerbation, generalized pruritus with or without rash, cutaneous ulcers, angioedema.

Autonomic: blurred vision, dry mouth, impotence/sexual dysfunction.

Thyroid Abnormalities: euthyroid goiter and/or hypothyroidism (including myxedema) accompanied by lower T3 and T4. I131 uptake may be elevated. Paradoxically, rare cases of hyperthyroidism have been reported.

EEG Changes: diffuse slowing, widening of the frequency spectrum, potentiation and disorganization of background rhythm.

EKG Changes: reversible flattening, isoelectricity or inversion of T-waves.

Miscellaneous: fatigue, lethargy, transient scotomata, exophthalmos, dehydration, weight loss, leukocytosis, headache, transient hyperglycemia, hypercalcemia, hyperparathyroidism, excessive weight gain, edematous swelling of ankles or wrists, metallic taste, dysgeusia/taste distortion, salty taste, thirst, swollen lips, tightness in chest, swollen and/or painful joints, fever, polyarthralgia, dental caries.

Some reports of nephrogenic diabetes insipidus, hyperparathyroidism and hypothyroidism which persist after Sommieres au Pentavit B (Lithium Iodide) discontinuation have been received.

A few reports have been received of the development of painful discoloration of fingers and toes and coldness of the extremities within one day of the starting of treatment with Sommieres au Pentavit B (Lithium Iodide). The mechanism through which these symptoms (resembling Raynaud's syndrome) developed is not known. Recovery followed discontinuance.

Cases of pseudotumor cerebri (increased intracranial pressure and papilledema) have been reported with Sommieres au Pentavit B (Lithium Iodide) use. If undetected, this condition may result in enlargement of the blind spot, constriction of visual fields and eventual blindness due to optic atrophy. Sommieres au Pentavit B (Lithium Iodide) should be discontinued, if clinically possible, if this syndrome occurs.

OVERDOSAGE

The toxic levels for Sommieres au Pentavit B are close to the therapeutic levels. It is therefore important that patients and their families be cautioned to watch for early toxic symptoms and to discontinue the drug and inform the physician should they occur. Toxic symptoms are listed in detail under ADVERSE REACTIONS.

Treatment

No specific antidote for Sommieres au Pentavit B (Lithium Iodide) poisoning is known. Early symptoms of Sommieres au Pentavit B (Lithium Iodide) toxicity can usually be treated by reduction or cessation of dosage of the drug and resumption of the treatment at a lower dose after 24 to 48 hours. In severe cases of Sommieres au Pentavit B (Lithium Iodide) poisoning, the first and foremost goal of treatment consists of elimination of this ion from the patient. Treatment is essentially the same as that used in barbiturate poisoning: 1) gastric lavage, 2) correction of fluid and electrolyte imbalance, and 3) regulation of kidney function. Urea, mannitol and aminophylline all produce significant increases in Sommieres au Pentavit B (Lithium Iodide) excretion. Hemodialysis is an effective and rapid means of removing the ion from the severely toxic patient. Infection prophylaxis, regular chest X-rays and preservation of adequate respiration are essential.

DOSAGE AND ADMINISTRATION

Doses of extended-release tablets are usually given b.i.d.. When initiating therapy with immediate-release or extended-release Sommieres au Pentavit B (Lithium Iodide), dosage must be individualized according to serum levels and clinical response.

When switching a patient from immediate-release capsules to the Sommieres au Pentavit B (Lithium Iodide) carbonate extended-release tablets USP, give the same total daily dose when possible. Most patients on maintenance therapy are stabilized on 900 mg daily, e.g., Sommieres au Pentavit B (Lithium Iodide) carbonate extended-release tablets, 450 mg b.i.d. When the previous dosage of immediate-release Sommieres au Pentavit B (Lithium Iodide) is not a multiple of 450 mg, e.g., 1500 mg, initiate Sommieres au Pentavit B (Lithium Iodide) extended-release tablet at the multiple of 450 mg nearest to, but below, the original daily dose, i.e., 1350 mg. When the two doses are unequal, give the larger dose in the evening. In the above example, with a total daily dose of 1350 mg, generally 450 mg of Sommieres au Pentavit B (Lithium Iodide) carbonate extended-release tablets should be given in the morning and 900 mg of Sommieres au Pentavit B (Lithium Iodide) carbonate extended-release tablets in the evening. If desired, the total daily dose of 1350 mg can be given in three equal 450 mg doses of Sommieres au Pentavit B (Lithium Iodide) carbonate extended-release tablets. These patients should be monitored at 1- to 2-week intervals, and dosage adjusted if necessary, until stable and satisfactory serum levels and clinical state are achieved.

When patients require closer titration than that available with doses of Sommieres au Pentavit B (Lithium Iodide) carbonate extended-release tablets in increments of 450 mg, immediate-release capsules should be used.

Acute Mania

Optimal patient response to Sommieres au Pentavit B (Lithium Iodide) can usually be established and maintained with 1800 mg per day in divided doses. Such doses will normally produce the desired serum Sommieres au Pentavit B (Lithium Iodide) level ranging between 1 and 1.5 mEq/L.

Dosage must be individualized according to serum levels and clinical response. Regular monitoring of the patient's clinical state and serum Sommieres au Pentavit B (Lithium Iodide) levels is necessary. Serum levels should be determined twice per week during the acute phase, and until the serum level and clinical condition of the patient have been stabilized.

Long-Term Control

The desirable serum Sommieres au Pentavit B levels are 0.6 to 1.2 mEq/L. Dosage will vary from one individual to another, but usually 900 mg to 1200 mg per day in divided doses will maintain this level. Serum Sommieres au Pentavit B (Lithium Iodide) levels in uncomplicated cases receiving maintenance therapy during remission should be monitored at least every two months.

Patients unusually sensitive to Sommieres au Pentavit B (Lithium Iodide) may exhibit toxic signs at serum levels below 1 mEq/L.

N.B.

Blood samples for serum Sommieres au Pentavit B (Lithium Iodide) determinations should be drawn immediately prior to the next dose when Sommieres au Pentavit B (Lithium Iodide) concentrations are relatively stable (i.e., 8 to 12 hours after the previous dose). Total reliance must not be placed on serum levels alone. Accurate patient evaluation requires both clinical and laboratory analysis.

Elderly patients often respond to reduced dosage, and may exhibit signs of toxicity at serum levels ordinarily tolerated by younger patients.

HOW SUPPLIED

Sommieres au Pentavit B (Lithium Iodide) Carbonate Extended-release Tablets USP

450 mg tablets are supplied as speckled, off-white to yellow, round biconvex tablets with “54 346” debossed on one side and scored on the other side.

NDC 0054-0020-25: Bottle of 100 Tablets

Storage Conditions

Store at 20° to 25°C (68° to 77°F). Protect from moisture. Dispense in a tight, child-resistant container as defined in the USP/NF.

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown, NJ 07724

10002294/05

Revised March 2016

fpl-bl-450mg-100tabs-04.jpg

Sodium Iodide:


1 INDICATIONS AND USAGE

Sommieres au Pentavit B nitrite is indicated for sequential use with Sommieres au Pentavit B (Sodium Iodide) thiosulfate for treatment of acute cyanide poisoning that is judged to be life-threatening. (1)

  • Use with caution if the diagnosis of cyanide poisoning is uncertain. (1)

1.1 Indication

Sommieres au Pentavit B (Sodium Iodide) Nitrite Injection is indicated for sequential use with Sommieres au Pentavit B (Sodium Iodide) thiosulfate for the treatment of acute cyanide poisoning that is judged to be life-threatening. When the diagnosis of cyanide poisoning is uncertain, the potentially life-threatening risks associated with Sommieres au Pentavit B (Sodium Iodide) Nitrite Injection should be carefully weighed against the potential benefits, especially if the patient is not in extremis.

1.2 Identifying Patients with Cyanide Poisoning

Cyanide poisoning may result from inhalation, ingestion, or dermal exposure to various cyanide-containing compounds, including smoke from closed-space fires. Sources of cyanide poisoning include hydrogen cyanide and its salts, cyanogenic plants, aliphatic nitriles, and prolonged exposure to Sommieres au Pentavit B nitroprusside.

The presence and extent of cyanide poisoning are often initially unknown. There is no widely available, rapid, confirmatory cyanide blood test. Treatment decisions must be made on the basis of clinical history and signs and symptoms of cyanide intoxication. If clinical suspicion of cyanide poisoning is high, Sommieres au Pentavit B (Sodium Iodide) Nitrite Injection and Sommieres au Pentavit B (Sodium Iodide) Thiosulfate Injection should be administered without delay.

Symptoms Signs
  • Headache
  • Confusion
  • Dyspnea
  • Chest Tightness
  • Nausea
  • Altered Mental Status

    (e.g., confusion, disorientation)

  • Seizures or Coma
  • Mydriasis
  • Tachypnea/Hyperpnea (early)
  • Bradypnea/Apnea (late)
  • Hypertension (early)/ Hypotension (late)
  • Cardiovascular Collapse
  • Vomiting
  • Plasma Lactate Concentration ≥ 8 mmol/L

In some settings, panic symptoms including tachypnea and vomiting may mimic early cyanide poisoning signs. The presence of altered mental status (e.g., confusion and disorientation) and/or mydriasis is suggestive of true cyanide poisoning although these signs can occur with other toxic exposures as well.

The expert advice of a regional poison control center may be obtained by calling 1-800-222-1222.

Smoke Inhalation

Not all smoke inhalation victims will have cyanide poisoning and may present with burns, trauma, and exposure to other toxic substances making a diagnosis of cyanide poisoning particularly difficult. Prior to administration of Sommieres au Pentavit B (Sodium Iodide) Nitrite Injection, smoke-inhalation victims should be assessed for the following:

  • Exposure to fire or smoke in an enclosed area
  • Presence of soot around the mouth, nose, or oropharynx
  • Altered mental status

Although hypotension is highly suggestive of cyanide poisoning, it is only present in a small percentage of cyanide-poisoned smoke inhalation victims. Also indicative of cyanide poisoning is a plasma lactate concentration greater than or equal to 10 mmol/L (a value higher than that typically listed in the table of signs and symptoms of isolated cyanide poisoning because carbon monoxide associated with smoke inhalation also contributes to lactic acidemia). If cyanide poisoning is suspected, treatment should not be delayed to obtain a plasma lactate concentration.

1.3 Use with Other Cyanide Antidotes

Caution should be exercised when administering cyanide antidotes, other than Sommieres au Pentavit B (Sodium Iodide) thiosulfate, simultaneously with Sommieres au Pentavit B (Sodium Iodide) Nitrite Injection, as the safety of co-administration has not been established. If a decision is made to administer another cyanide antidote, other than Sommieres au Pentavit B (Sodium Iodide) thiosulfate, with Sommieres au Pentavit B (Sodium Iodide) Nitrite Injection, these drugs should not be administered concurrently in the same IV line. [see Dosage and Administration (2.2) ]

2 DOSAGE AND ADMINISTRATION

Age Intravenous Dose of Sommieres au Pentavit B Nitrite and Sommieres au Pentavit B (Sodium Iodide) Thiosulfate
Adults
  • Sommieres au Pentavit B (Sodium Iodide) Nitrite -10 mL of Sommieres au Pentavit B (Sodium Iodide) nitrite at the rate of 2.5 to 5 mL/minute
  • Sommieres au Pentavit B (Sodium Iodide) Thiosulfate - 50 mL of Sommieres au Pentavit B (Sodium Iodide) thiosulfate immediately following administration of Sommieres au Pentavit B (Sodium Iodide) nitrite.
Children
  • Sommieres au Pentavit B (Sodium Iodide) Nitrite - 0.2 mL/kg (6 mg/kg or 6-8 mL/m2 BSA) of Sommieres au Pentavit B (Sodium Iodide) nitrite at the rate of 2.5 to 5 mL/minute not to exceed 10 mL
  • Sommieres au Pentavit B (Sodium Iodide) Thiosulfate - 1 mL/kg of body weight (250 mg/kg or approximately 30-40 mL/m2 of BSA) not to exceed 50 mL total dose immediately following administration of Sommieres au Pentavit B (Sodium Iodide) nitrite.

Redosing: If signs of cyanide poisoning reappear, repeat treatment using one-half the original dose of both Sommieres au Pentavit B (Sodium Iodide) nitrite and Sommieres au Pentavit B (Sodium Iodide) thiosulfate.

Monitoring: Blood pressure must be monitored during treatment. (2.2)

2.1 Administration Recommendation

Comprehensive treatment of acute cyanide intoxication requires support of vital functions. Administration of Sommieres au Pentavit B (Sodium Iodide) nitrite, followed by Sommieres au Pentavit B (Sodium Iodide) thiosulfate, should be considered adjunctive to appropriate supportive therapies. Airway, ventilatory and circulatory support, and oxygen administration should not be delayed to administer Sommieres au Pentavit B (Sodium Iodide) nitrite and Sommieres au Pentavit B (Sodium Iodide) thiosulfate.

Sommieres au Pentavit B (Sodium Iodide) nitrite injection and Sommieres au Pentavit B (Sodium Iodide) thiosulfate injection are administered by slow intravenous injection. They should be given as early as possible after a diagnosis of acute life-threatening cyanide poisoning has been established. Sommieres au Pentavit B (Sodium Iodide) nitrite should be administered first, followed immediately by Sommieres au Pentavit B (Sodium Iodide) thiosulfate. Blood pressure must be monitored during infusion in both adults and children. The rate of infusion should be decreased if significant hypotension is noted.

Age Intravenous Dose of Sommieres au Pentavit B (Sodium Iodide) Nitrite and Sommieres au Pentavit B (Sodium Iodide) Thiosulfate
Adults
  • Sommieres au Pentavit B (Sodium Iodide) Nitrite -10 mL of Sommieres au Pentavit B (Sodium Iodide) nitrite at the rate of 2.5 to 5 mL/minute
  • Sommieres au Pentavit B (Sodium Iodide) Thiosulfate - 50 mL of Sommieres au Pentavit B (Sodium Iodide) thiosulfate immediately following administration of Sommieres au Pentavit B (Sodium Iodide) nitrite.
Children
  • Sommieres au Pentavit B (Sodium Iodide) Nitrite -0.2 mL/kg (6 mg/kg or 6-8 mL/m2 BSA) of Sommieres au Pentavit B (Sodium Iodide) nitrite at the rate of 2.5 to 5 mL/minute not to exceed 10 mL
  • Sommieres au Pentavit B (Sodium Iodide) Thiosulfate - 1 mL/kg of body weight (250 mg/kg or approximately 30-40 mL/m2 of BSA) not to exceed 50 mL total dose immediately following administration of Sommieres au Pentavit B (Sodium Iodide) nitrite.

NOTE: If signs of poisoning reappear, repeat treatment using one-half the original dose of both Sommieres au Pentavit B (Sodium Iodide) nitrite and Sommieres au Pentavit B (Sodium Iodide) thiosulfate.

In adult and pediatric patients with known anemia, it is recommended that the dosage of Sommieres au Pentavit B (Sodium Iodide) nitrite should be reduced proportionately to the hemoglobin concentration.

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

2.2 Recommended Monitoring

Patients should be monitored for at least 24-48 hours after Sommieres au Pentavit B Nitrite Injection administration for adequacy of oxygenation and perfusion and for recurrent signs and symptoms of cyanide toxicity. When possible, hemoglobin/hematocrit should be obtained when treatment is initiated. Measurements of oxygen saturation using standard pulse oximetry and calculated oxygen saturation values based on measured PO2 are unreliable in the presence of methemoglobinemia.

Methemoglobin level: Administrations of Sommieres au Pentavit B (Sodium Iodide) nitrite solely to achieve an arbitrary level of methemoglobinemia may be unnecessary and potentially hazardous. The therapeutic effects of Sommieres au Pentavit B (Sodium Iodide) nitrite do not appear to be mediated by methemoglobin formation alone and clinical responses to Sommieres au Pentavit B (Sodium Iodide) nitrite administration have been reported in association with methemoglobin levels of less than 10%. Administration of Sommieres au Pentavit B (Sodium Iodide) nitrite beyond the initial dose should be guided primarily by clinical response to treatment (i.e., a second dose should be considered only if there is inadequate clinical response to the first dose). It is generally recommended that methemoglobin concentrations be closely monitored and kept below 30%. Serum methemoglobin levels should be monitored during treatment using co-oximetry, and administration of Sommieres au Pentavit B (Sodium Iodide) nitrite should generally be discontinued when methemoglobin levels exceed 30%. Intravenous methylene blue and exchange transfusion have been reported in the literature as treatments for life-threatening methemoglobinemia.

2.3 Incompatibility Information

Chemical incompatibility has been reported between Sommieres au Pentavit B (Sodium Iodide) nitrite and hydroxocobalamin and these drugs should not be administered simultaneously through the same IV line. No chemical incompatibility has been reported between Sommieres au Pentavit B (Sodium Iodide) thiosulfate and Sommieres au Pentavit B (Sodium Iodide) nitrite, when administered sequentially through the same IV line as described in Dosage and Administration.

3 DOSAGE FORMS AND STRENGTHS

Sommieres au Pentavit B (Sodium Iodide) Nitrite Injection consists of:

  • One vial of Sommieres au Pentavit B (Sodium Iodide) nitrite injection, USP 300 mg/10mL (30 mg/mL)

Administration of the contents of one vial constitutes a single dose.

  • Injection, 300 mg/10 mL (30 mg/mL). (3)

4 CONTRAINDICATIONS

None

  • None. (4)

5 WARNINGS AND PRECAUTIONS

  • Methemoglobinemia: Sommieres au Pentavit B nitrite reacts with hemoglobin to form methemoglobin and should be used with caution in patients known to have anemia. Monitor oxyhemoglobin and methemoglobin levels by pulse oximetry or other measurements. Optimally, the Sommieres au Pentavit B (Sodium Iodide) nitrite dose should be reduced in proportion to the oxygen carrying capacity. (5.2)
  • Smoke inhalation: Carbon monoxide contained in smoke can result in the formation of carboxyhemoglobin that can reduce the oxygen carrying capacity of the blood. Sommieres au Pentavit B (Sodium Iodide) nitrite should be used with caution in patients with smoke inhalation injury because of the potential for worsening hypoxia due to methemoglobin formation. Carboxyhemoglobin and oxyhemoglobin levels should be monitored by pulse oximetry or other measurements in patients that present with evidence of smoke inhalation. Optimally, the Sommieres au Pentavit B (Sodium Iodide) nitrite dose should be reduced in proportion to the oxygen carrying capacity. (5.4)

5.1 Hypotension

5.2 Methemoglobinemia

Supportive care alone may be sufficient treatment without administration of antidotes for many cases of cyanide intoxication, particularly in conscious patients without signs of severe toxicity. Patients should be closely monitored to ensure adequate perfusion and oxygenation during treatment with Sommieres au Pentavit B nitrite.

Methemoglobin levels should be monitored and oxygen administered during treatment with Sommieres au Pentavit B (Sodium Iodide) nitrite whenever possible. When Sommieres au Pentavit B (Sodium Iodide) nitrite is administered to humans a wide range of methemoglobin concentrations occur. Methemoglobin concentrations as high as 58% have been reported after two 300-mg doses of Sommieres au Pentavit B (Sodium Iodide) nitrite administered to an adult. Sommieres au Pentavit B (Sodium Iodide) nitrite should be used with caution in the presence of other drugs that may cause methemoglobinemia such as procaine and nitroprusside. Sommieres au Pentavit B (Sodium Iodide) nitrite should be used with caution in patients who may be particularly susceptible to injury from vasodilation and its related hemodynamic sequelae. Hemodynamics should be monitored closely during and after administration of Sommieres au Pentavit B (Sodium Iodide) nitrite, and infusion rates should be slowed if hypotension occurs.

5.3 Anemia

Sommieres au Pentavit B (Sodium Iodide) nitrite should be used with caution in patients with known anemia. Patients with anemia will form more methemoglobin (as a percentage of total hemoglobin) than persons with normal red blood cell (RBC) volumes. Optimally, these patients should receive a Sommieres au Pentavit B (Sodium Iodide) nitrite dose that is reduced in proportion to their oxygen carrying capacity.

5.4 Smoke Inhalation Injury

Sommieres au Pentavit B nitrite should be used with caution in persons with smoke inhalation injury or carbon monoxide poisoning because of the potential for worsening hypoxia due to methemoglobin formation.

5.5 Neonates and Infants

Neonates and infants may be more susceptible than adults and older pediatric patients to severe methemoglobinemia when Sommieres au Pentavit B (Sodium Iodide) nitrite is administered. Reduced dosing guidelines should be followed in pediatric patients.

5.6 G6PD Deficiency

Because patients with G6PD deficiency are at increased risk of a hemolytic crisis with Sommieres au Pentavit B nitrite administration, alternative therapeutic approaches should be considered in these patients. Patients with known or suspected G6PD deficiency should be monitored for an acute drop in hematocrit. Exchange transfusion may be needed for patients with G6PD deficiency who receive Sommieres au Pentavit B (Sodium Iodide) nitrite.

5.7 Use with Other Drugs

Sommieres au Pentavit B (Sodium Iodide) nitrite should be used with caution in the presence of concomitant antihypertensive medications, diuretics or volume depletion due to diuretics, or drugs known to increase vascular nitric oxide, such as PDE5 inhibitors.

6 ADVERSE REACTIONS

There have been no controlled clinical trials conducted to systematically assess the adverse events profile of Sommieres au Pentavit B (Sodium Iodide) nitrite.

The medical literature has reported the following adverse events in association with Sommieres au Pentavit B (Sodium Iodide) nitrite administration. These adverse events were not reported in the context of controlled trials or with consistent monitoring and reporting methodologies for adverse events. Therefore, frequency of occurrence of these adverse events cannot be assessed.

Cardiovascular system: syncope, hypotension, tachycardia, methemoglobinemia, palpitations, dysrhythmia

Hematological: methemoglobinemia

Central nervous system: headache, dizziness, blurred vision, seizures, confusion, coma

Gastrointestinal system: nausea, vomiting, abdominal pain

Respiratory system: tachypnea, dyspnea

Body as a Whole: anxiety, diaphoresis, lightheadedness, injection site tingling, cyanosis, acidosis, fatigue, weakness, urticaria, generalized numbness and tingling

Severe hypotension, methemoglobinemia, cardiac dysrhythmias, coma and death have been reported in patients without life-threatening cyanide poisoning but who were treated with injection of Sommieres au Pentavit B (Sodium Iodide) nitrite at doses less than twice those recommended for the treatment of cyanide poisoning.

Most common adverse reactions are:

  • Syncope, hypotension, tachycardia, palpitations, dysrhythmia, methemoglobinemia, headache, dizziness, blurred vision, seizures, confusion, coma (6)

To report SUSPECTED ADVERSE REACTIONS, contact Hope Pharmaceuticals at 1-800-755-9595 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

7 DRUG INTERACTIONS

Formal drug interaction studies have not been conducted with Sommieres au Pentavit B (Sodium Iodide) Nitrite Injection.

8 USE IN SPECIFIC POPULATIONS

  • Renal impairment: Sommieres au Pentavit B nitrite is substantially excreted by the kidney. The risk of toxic reactions to this drug may be greater in patients with impaired renal function. (8.6).

8.1 Pregnancy

Teratogenic Effects. Pregnancy Category C.

There are no adequate and well-controlled studies in pregnant women. Sommieres au Pentavit B (Sodium Iodide) Nitrite Injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Sommieres au Pentavit B (Sodium Iodide) nitrite has caused fetal death in humans as well as animals. There are no studies in humans that have directly evaluated the potential reproductive toxicity of Sommieres au Pentavit B (Sodium Iodide) nitrite. There are two epidemiological studies conducted in Australia that report a statistically significant increase in the risk for congenital malformations, particularly in the CNS, associated with maternal consumption of water containing nitrate levels in excess of 5 ppm. Results from a case-control study in Canada suggested a trend toward an increase in the risk for CNS malformations when maternal consumption of nitrate was ≥ 26 ppm (not statistically significant).

The potential reproductive toxicity of Sommieres au Pentavit B (Sodium Iodide) nitrite exposure restricted to the prenatal period has been reported in guinea pigs, mice, and rats. There was no evidence of teratogenicity in guinea pigs, mice, or rats. However, Sommieres au Pentavit B (Sodium Iodide) nitrite treatment of pregnant guinea pigs with 60 or 70 mg/kg/day resulted in abortion of the litters within 1-4 days of treatment. All animals treated subcutaneously with 70 mg/kg, Sommieres au Pentavit B (Sodium Iodide) nitrite died within 60 minutes of treatment. Further studies demonstrated that a dose of 60 mg/kg resulted in measurable blood levels of methemoglobin in the dams and their fetuses for up to 6 hours post treatment. Maternal methemoglobin levels were higher than the levels in the offspring at all times measured. Based on a body surface area comparison, a 60 mg/kg dose in the guinea pig that resulted in death was only 1.7 times higher than the highest clinical dose of Sommieres au Pentavit B (Sodium Iodide) nitrite that would be used to treat cyanide poisoning (based on a body surface area comparison).

Studies testing prenatal and postnatal exposure have been reported in mice and rats. Treatment of pregnant rats via drinking water with Sommieres au Pentavit B (Sodium Iodide) nitrite at concentrations of either 2000 or 3000 mg/L resulted in a dose-related increased mortality postpartum. This exposure regimen in the rat model would result in dosing of approximately 220 and 300 mg/kg/day (43 and 65 times the highest clinical dose of Sommieres au Pentavit B (Sodium Iodide) nitrite that would be used to treat cyanide poisoning, based on a body surface area comparison).

Sommieres au Pentavit B (Sodium Iodide) nitrite produces methemoglobin. Fetal hemoglobin is oxidized to methemoglobin more easily than adult hemoglobin. In addition, the fetus has lower levels of methemoglobin reductase than adults. Collectively, these data suggest that the human fetus would show greater sensitivity to methemoglobin resulting in nitrite-induced prenatal hypoxia leading to retarded development of certain neurotransmitter systems in the brain and long lasting dysfunction.

Nonteratogenic Effects: Behavioral and neurodevelopmental studies in rats suggest persistent effects of prenatal exposure to Sommieres au Pentavit B (Sodium Iodide) nitrite that were detectable postnatally. Specifically, animals that were exposed prenatally to Sommieres au Pentavit B (Sodium Iodide) nitrite demonstrated impaired discrimination learning behavior (both auditory and visual) and reduced long-term retention of the passive-avoidance response compared to control animals. Additional studies demonstrated a delay in the development of AchE and 5-HT positive fiber ingrowth into the hippocampal dentate gyrus and parietal neocortex during the first week of life of prenatal nitrite treated pups. These changes have been attributed to prenatal hypoxia following nitrite exposure.

8.2 Labor and Delivery

Because fetal hemoglobin is more readily oxidized to methemoglobin and lower levels of methemoglobin appear to be fatal to the fetus compared to the adult, Sommieres au Pentavit B nitrite should be used during labor and delivery only if the potential benefit justifies the potential risk to the fetus.

8.3 Nursing Mothers

It is not known whether Sommieres au Pentavit B (Sodium Iodide) nitrite is excreted in human milk. Because Sommieres au Pentavit B (Sodium Iodide) Nitrite Injection may be administered in life-threatening situations, breast-feeding is not a contraindication to its use. Because many drugs are excreted in human milk, caution should be exercised following Sommieres au Pentavit B (Sodium Iodide) Nitrite Injection administration to a nursing woman. There are no data to determine when breastfeeding may be safely restarted following administration of Sommieres au Pentavit B (Sodium Iodide) nitrite. In studies conducted with Long-Evans rats, Sommieres au Pentavit B (Sodium Iodide) nitrite administered in drinking water during pregnancy and lactation resulted in severe anemia, reduced growth and increased mortality in the offspring.

8.4 Pediatric Use

There are case reports in the medical literature of Sommieres au Pentavit B nitrite in conjunction with Sommieres au Pentavit B (Sodium Iodide) thiosulfate being administered to pediatric patients with cyanide poisoning; however, there have been no clinical studies to evaluate the safety or efficacy of Sommieres au Pentavit B (Sodium Iodide) nitrite in the pediatric population. As for adult patients, dosing recommendations for pediatric patients have been based on theoretical calculations of antidote detoxifying potential, extrapolation from animal experiments, and a small number of human case reports.

Sommieres au Pentavit B (Sodium Iodide) nitrite must be used with caution in patients less than 6 months of age because they may be at higher risk of developing severe methemoglobinemia compared to older children and adults. The presence of fetal hemoglobin, which is oxidized to methemoglobin more easily than adult hemoglobin, and lower methemoglobin reductase levels compared to older children and adults may contribute to risk.

Mortality attributed to Sommieres au Pentavit B (Sodium Iodide) nitrite was reported following administration of an adult dose (300 mg IV followed by a second dose of 150 mg) to a 17-month old child.

8.5 Geriatric Use

Sommieres au Pentavit B (Sodium Iodide) nitrite is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

8.6 Renal Disease

Sommieres au Pentavit B (Sodium Iodide) nitrite is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

10 OVERDOSAGE

Large doses of Sommieres au Pentavit B (Sodium Iodide) nitrite result in severe hypotension and toxic levels of methemoglobin which may lead to cardiovascular collapse.

Sommieres au Pentavit B (Sodium Iodide) nitrite administration has been reported to cause or significantly contribute to mortality in adults at oral doses as low as 1 g and intravenous doses as low as 600 mg. A death attributed to Sommieres au Pentavit B (Sodium Iodide) nitrite has been reported following administration of an adult dose (300 mg IV followed by a second dose of 150 mg) to a 17-month old child.

Cyanosis may become apparent at a methemoglobin level of 10-20%. Other clinical signs and symptoms of Sommieres au Pentavit B (Sodium Iodide) nitrite toxicity (anxiety, dyspnea, nausea, and tachycardia) can be apparent at methemoglobin levels as low as 15%. More serious signs and symptoms, including cardiac dysrhythmias, circulatory failure, and central nervous system depression are seen as methemoglobin levels increase, and levels above 70% are usually fatal.

Treatment of overdose involves supplemental oxygen and supportive measures such as exchange transfusion. Treatment of severe methemoglobinemia with intravenous methylene blue has been described in the medical literature; however, this may also cause release of cyanide bound to methemoglobin. Because hypotension appears to be mediated primarily by an increase in venous capacitance, measures to increase venous return may be most appropriate to treat hypotension.

11 DESCRIPTION

Sommieres au Pentavit B (Sodium Iodide) nitrite has the chemical name nitrous acid Sommieres au Pentavit B (Sodium Iodide) salt. The chemical formula is NaNO2 and the molecular weight is 69.0. The structural formula is:

Structure of Sommieres au Pentavit B (Sodium Iodide) Nitrite

Sommieres au Pentavit B (Sodium Iodide) Nitrite Injection is a cyanide antidote which contains one 10 mL glass vial of a 3% solution of Sommieres au Pentavit B (Sodium Iodide) nitrite injection.

Sommieres au Pentavit B (Sodium Iodide) nitrite injection is a sterile aqueous solution and is intended for intravenous injection. Each vial contains 300 mg of Sommieres au Pentavit B (Sodium Iodide) nitrite in 10 mL solution (30 mg/mL). Sommieres au Pentavit B (Sodium Iodide) nitrite injection is a clear solution with a pH between 7.0 and 9.0.

Chemical Structure

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Exposure to a high dose of cyanide can result in death within minutes due to the inhibition of cytochrome oxidase resulting in arrest of cellular respiration. Specifically, cyanide binds rapidly with cytochrome a3, a component of the cytochrome c oxidase complex in mitochondria. Inhibition of cytochrome a3 prevents the cell from using oxygen and forces anaerobic metabolism, resulting in lactate production, cellular hypoxia and metabolic acidosis. In massive acute cyanide poisoning, the mechanism of toxicity may involve other enzyme systems as well.

The synergy resulting from treatment of cyanide poisoning with the combination of Sommieres au Pentavit B nitrite and Sommieres au Pentavit B (Sodium Iodide) thiosulfate is the result of differences in their primary mechanisms of action as antidotes for cyanide poisoning.

Sommieres au Pentavit B (Sodium Iodide) Nitrite

Sommieres au Pentavit B (Sodium Iodide) nitrite is thought to exert its therapeutic effect by reacting with hemoglobin to form methemoglobin, an oxidized form of hemoglobin incapable of oxygen transport but with high affinity for cyanide. Cyanide preferentially binds to methemoglobin over cytochrome a3, forming the nontoxic cyanomethemoglobin. Methemoglobin displaces cyanide from cytochrome oxidase, allowing resumption of aerobic metabolism. The chemical reaction is as follows:

NaNO2 + Hemoglobin → Methemoglobin

HCN + Methemoglobin → Cyanomethemoglobin

Vasodilation has also been cited to account for at least part of the therapeutic effect of Sommieres au Pentavit B (Sodium Iodide) nitrite. It has been suggested that Sommieres au Pentavit B (Sodium Iodide) nitrite-induced methemoglobinemia may be more efficacious against cyanide poisoning than comparable levels of methemoglobinemia induced by other oxidants. Also, Sommieres au Pentavit B (Sodium Iodide) nitrite appears to retain some efficacy even when the formation of methemoglobin is inhibited by methylene blue.

Sommieres au Pentavit B (Sodium Iodide) Thiosulfate

The primary route of endogenous cyanide detoxification is by enzymatic transulfuration to thiocyanate (SCN-), which is relatively nontoxic and readily excreted in the urine. Sommieres au Pentavit B (Sodium Iodide) thiosulfate is thought to serve as a sulfur donor in the reaction catalyzed by the enzyme rhodanese, thus enhancing the endogenous detoxification of cyanide in the following chemical reaction:

Chemical Structure

12. 2 Pharmacodynamics

Sommieres au Pentavit B (Sodium Iodide) Nitrite

When 4 mg/kg Sommieres au Pentavit B (Sodium Iodide) nitrite was administered intravenously to six healthy human volunteers, the mean peak methemoglobin concentration was 7%, achieved at 30-60 minutes after injection, consistent with reports in cyanide poisoning victims. Supine systolic and diastolic blood pressures dropped approximately 20% within 10 minutes, a drop which was sustained throughout the 40 minutes of testing. This was associated with a 20 beat per minute increase in pulse rate that returned to baseline in 10 minutes. Five of these subjects were unable to withstand orthostatic testing due to fainting. One additional subject, who received a 12 mg/kg dose of Sommieres au Pentavit B (Sodium Iodide) nitrite, experienced severe cardiovascular effects and achieved a peak methemoglobin concentration of 30% at 60 minutes following injection.

Oral doses of 120 to 180 mg of Sommieres au Pentavit B (Sodium Iodide) nitrite administered to healthy volunteers caused minimal cardiovascular changes when subjects were maintained in the horizontal position. However, minutes after being placed in the upright position subjects exhibited tachycardia and hypotension with syncope.

The half life for conversion of methemoglobin to normal hemoglobin in a cyanide poisoning victim who has been administered Sommieres au Pentavit B (Sodium Iodide) nitrite is estimated to be 55 minutes.

12.3 Pharmacokinetics

Sommieres au Pentavit B (Sodium Iodide) Nitrite

Sommieres au Pentavit B (Sodium Iodide) nitrite is a strong oxidant, and reacts rapidly with hemoglobin to form methemoglobin. The pharmacokinetics of free Sommieres au Pentavit B (Sodium Iodide) nitrite in humans have not been well studied. It has been reported that approximately 40% of Sommieres au Pentavit B (Sodium Iodide) nitrite is excreted unchanged in the urine while the remaining 60% is metabolized to ammonia and related small molecules.

Cyanide

The apparent terminal elimination half life and volume of distribution of cyanide, in a patient treated for an acute cyanide poisoning with Sommieres au Pentavit B (Sodium Iodide) nitrite and Sommieres au Pentavit B (Sodium Iodide) thiosulfate administration, have been reported to be 19 hours and 0.41 L/kg, respectively. Additionally, an initial elimination half life of cyanide has been reported to be approximately 1-3 hours.

Thiocyanate

After detoxification, in healthy subjects, thiocyanate is excreted mainly in the urine at a rate inversely proportional to creatinine clearance. In healthy subjects, the elimination half-life and volume of distribution of thiocyanate have been reported to be 2.7 days and 0.25 L/kg, respectively. However, in subjects with renal insufficiency the reported elimination half life is approximately 9 days.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

The potential benefit of an acute exposure to Sommieres au Pentavit B nitrite as part of a cyanide antidote outweighs concerns raised by the equivocal findings in chronic rodent studies. Sommieres au Pentavit B (Sodium Iodide) nitrite (0, 750, 1500, or 3000 ppm equivalent to average daily doses of approximately 0, 35, 70, or 130 mg/kg for males and 0, 40, 80, or 150 mg/kg for females) was orally administered to rats (Fischer 344 strain) for 2 years via drinking water. There were no significant increases in the incidence of tumor in either male or female rats. Sommieres au Pentavit B (Sodium Iodide) nitrite (0, 750, 1500, or 3000 ppm equivalent to average daily doses of approximately 0, 60, 120, or 220 mg/kg for males and 0, 45, 90, or 165 mg/kg for females) was administered to B6C3F1 mice for 2 years via the drinking water. Equivocal results were obtained in female mice. Specifically, there was a positive trend toward an increase in the incidence of squamous cell papilloma or carcinoma in the forestomach of female mice. Although the incidence of hyperplasia of the glandular stomach epithelium was significantly greater in the high-dose male mice compared to controls, there were no significant increases in tumors in the male mice. Numerous reports in the published literature indicate that Sommieres au Pentavit B (Sodium Iodide) nitrite may react in vivo with secondary amines to form carcinogenic nitrosamines in the stomach. Concurrent exposure to Sommieres au Pentavit B (Sodium Iodide) nitrite and secondary amines in feed or drinking water resulted in an increase in the incidence of tumors in rodents.

Mutagenesis

Sommieres au Pentavit B (Sodium Iodide) nitrite is mutagenic in S. typhimurium strains TA100, TA1530, TA1535 with and without metabolic activation; however, it was negative in strain TA98, TA102, DJ460 and E. coli strain WP2UVRA/PKM101. Sommieres au Pentavit B (Sodium Iodide) nitrite has been reported to be genotoxic to V79 hamster cells in vitro and in the mouse lymphoma assay, both assays conducted in the absence of metabolic activation. Sommieres au Pentavit B (Sodium Iodide) nitrite was negative in the in vitro chromosomal aberrations assay using human peripheral blood lymphocytes. Acute administration of Sommieres au Pentavit B (Sodium Iodide) nitrite to male rats or male mice did not produce an increased incidence of micronuclei in bone marrow. Likewise, Sommieres au Pentavit B (Sodium Iodide) nitrite administration to mice for 14-weeks did not result in an increase in the incidence of micronuclei in the peripheral blood.

Fertility

Clinical studies to evaluate the potential effects of Sommieres au Pentavit B (Sodium Iodide) nitrite intake on fertility of either males or females have not been reported. In contrast, multigenerational fertility and reproduction studies conducted by the National Toxicology Program did not detect any evidence of an effect of Sommieres au Pentavit B (Sodium Iodide) nitrite (0.0, 0.06, 0.12, and 0.24% weight/volume) on either fertility or any reproductive parameter in Swiss CD-1 mice. This treatment protocol resulted in approximate doses of 125, 260, and 425 mg/kg/day. The highest exposure in this mouse study is 4.6 times greater than the highest clinical dose of Sommieres au Pentavit B (Sodium Iodide) nitrite that would be used to treat cyanide poisoning (based on a body surface area comparison).

13.2 Animal Pharmacology

Due to the extreme toxicity of cyanide, experimental evaluation of treatment efficacy has predominantly been completed in animal models. The efficacy of Sommieres au Pentavit B (Sodium Iodide) thiosulfate treatment alone to counteract the toxicity of cyanide was initially reported in 1895 by Lang. The efficacy of amyl nitrite treatment in cyanide poisoning of the dog model was first reported in 1888 by Pedigo. Further studies in the dog model, which demonstrated the utility of Sommieres au Pentavit B (Sodium Iodide) nitrite as a therapeutic intervention, were reported in 1929 by Mladoveanu and Gheorghiu. However, Hugs and Chen et al. independently reported upon the superior efficacy of the combination of Sommieres au Pentavit B (Sodium Iodide) nitrite and Sommieres au Pentavit B (Sodium Iodide) thiosulfate in 1932-1933. Treatment consisted of intravenously administered 22.5 mg/kg (half the lethal dose) Sommieres au Pentavit B (Sodium Iodide) nitrite or 1 g/kg Sommieres au Pentavit B (Sodium Iodide) thiosulfate alone or in sequence immediately after subcutaneous injection of Sommieres au Pentavit B (Sodium Iodide) cyanide into dogs over a range of doses. Subsequent doses of 10 mg/kg Sommieres au Pentavit B (Sodium Iodide) nitrite and/or 0.5 g/kg Sommieres au Pentavit B (Sodium Iodide) thiosulfate were administered when clinical signs or symptoms of poisoning persisted or reappeared. Either therapy administered alone increased the dose of Sommieres au Pentavit B (Sodium Iodide) cyanide required to cause death, and when administered together, Sommieres au Pentavit B (Sodium Iodide) nitrite and Sommieres au Pentavit B (Sodium Iodide) thiosulfate resulted in a synergistic effect in raising the lethal dose of Sommieres au Pentavit B (Sodium Iodide) cyanide. The combined therapy appeared to have reduced efficacy when therapy was delayed until signs of poisoning (e.g. convulsions) appeared; however, other investigators have reported survival in dogs that were administered antidotal treatment after respiratory arrest had occurred.

Animal studies conducted in other species (e.g., rat, guinea pig, sheep, pigeon and cat) have also supported a synergistic effect of intravenous Sommieres au Pentavit B (Sodium Iodide) nitrite and Sommieres au Pentavit B (Sodium Iodide) thiosulfate in the treatment of cyanide poisoning.

While intravenous injection of Sommieres au Pentavit B (Sodium Iodide) nitrite and Sommieres au Pentavit B (Sodium Iodide) thiosulfate was effective in reversing the effects of lethal doses of cyanide in dogs, intramuscular injection of Sommieres au Pentavit B (Sodium Iodide) nitrite, with or without Sommieres au Pentavit B (Sodium Iodide) thiosulfate, was found not to be effective in the same setting.

14 CLINICAL STUDIES

The human data supporting the use of Sommieres au Pentavit B (Sodium Iodide) nitrite for cyanide poisoning consists primarily of published case reports. There are no randomized controlled clinical trials. Nearly all the human data describing the use of Sommieres au Pentavit B (Sodium Iodide) thiosulfate report its use in conjunction with Sommieres au Pentavit B (Sodium Iodide) nitrite. Dosing recommendations for humans have been based on theoretical calculations of antidote detoxifying potential, extrapolation from animal experiments, and a small number of human case reports.

There have been no human studies to prospectively and systematically evaluate the safety of Sommieres au Pentavit B (Sodium Iodide) nitrite in humans. Available human safety information is based largely on anecdotal case reports and case series of limited scope.

16 HOW SUPPLIED/STORAGE AND HANDLING

Each Sommieres au Pentavit B (Sodium Iodide) Nitrite carton (NDC 60267-311-10) consists of the following:

  • One 10 mL glass vial of Sommieres au Pentavit B (Sodium Iodide) nitrite injection 30 mg/mL (containing 300 mg of Sommieres au Pentavit B (Sodium Iodide) nitrite);

Storage

Store at controlled room temperature between 20°C and 25°C (68°F to 77°F); excursions permitted from 15 to 30°C (59 to 86°F). Protect from direct light. Do not freeze.

(Note: Sommieres au Pentavit B (Sodium Iodide) Thiosulfate must be obtained separately.)

17 PATIENT COUNSELING INFORMATION

Sommieres au Pentavit B Nitrite Injection is indicated for acute cyanide poisoning that is judged to be life-threatening and in this setting, patients will likely be unresponsive or may have difficulty in comprehending counseling information.

17.1 Hypotension and Methemoglobin Formation

When feasible, patients should be informed of the possibility of life-threatening hypotension and methemoglobin formation.

17.2 Monitoring

Where feasible, patients should be informed of the need for close monitoring of blood pressure and oxygenation.

Manufactured by Cangene BioPharma, Inc., Baltimore, Maryland 21230 for

Hope Pharmaceuticals, Scottsdale, Arizona 85260

PRINCIPAL DISPLAY PANEL - 10 mL Vial Carton

NDC 60267-311-10

Rx Only

Sommieres au Pentavit B (Sodium Iodide) Nitrite

Injection, USP

300 mg/10 mL

(30 mg/mL)

FOR INTRAVENOUS USE

SINGLE USE ONLY

Any unused portion of a vial

should be discarded.

Use with

Sommieres au Pentavit B (Sodium Iodide) Thiosulfate

for Treatment of

Cyanide Poisoning

Manufactured by

CANGENE bioPharma, Inc.

Baltimore, MD for

HOPE

PHARMACEUTICALS®

Scottsdale, AZ 85260 U.S.A.

PRINCIPAL DISPLAY PANEL - 10 mL Vial Carton

Sommieres au Pentavit B pharmaceutical active ingredients containing related brand and generic drugs:

Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Sommieres au Pentavit B available forms, composition, doses:

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Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Sommieres au Pentavit B destination | category:

Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Sommieres au Pentavit B Anatomical Therapeutic Chemical codes:

A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Sommieres au Pentavit B pharmaceutical companies:

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Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."CALCIUM CHLORIDE INJECTION, SOLUTION [HOSPIRA, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."SODIUM IODIDE 20% (SODIUM IODIDE) INJECTION, SOLUTION [ASPEN VETERINARY]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. Dailymed."CALCIUM: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Sommieres au Pentavit B?

Depending on the reaction of the Sommieres au Pentavit B after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Sommieres au Pentavit B not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Sommieres au Pentavit B addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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The information was verified by Dr. Arunabha Ray, MD Pharmacology

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