Albumin (Human) 20%

FULL PRESCRIBING INFORMATION

Indications and Usage for Albumin (Human) 20%

Hypovolemia

Albumin (Human) 20% is indicated in the emergency treatment of hypovolemia with or without shock. Its effectiveness in reversing hypovolemia depends largely upon its ability to draw interstitial fluid into the circulation. It is most effective in patients who are well hydrated. When blood volume deficit is the result of hemorrhage, compatible red blood cells or whole blood should be administered as quickly as possible. [1, 2]

When hypovolemia is long standing and hypoalbuminemia exists accompanied by adequate hydration or edema, 20% - 25% albumin solutions should be used. [1 ]

Hypoalbuminemia

For subjects with hypoalbuminemia who are critically ill and/or are bleeding actively, ALBUMIN (HUMAN) 20% infusions may be indicated. [3 ] When albumin deficit is the result of excessive protein loss, the effect of administration of Albumin (Human) 20% will be temporary unless the underlying disorder is reversed.

Prevention of Central Volume Depletion after Paracentesis due to Cirrhotic Ascites (Treatment Adjunct)

Albumin (Human) 20% may be used to maintain cardiovascular function following the removal of large volumes of ascitic fluid after paracentesis due to cirrhotic ascites. [2 ]

Ovarian Hyperstimulation Syndrome (OHSS)

Albumin (Human) 20% may be used as a plasma expander in fluid management relating to severe forms of ovarian hyperstimulation syndrome (OHSS). [7, 8]

Adult Respiratory Distress Syndrome (ARDS) (Treatment Adjunct)

Albumin (Human) 20% infusions may be indicated in conjunction with diuretics to correct the fluid volume overload associated with ARDS. [5 ]

Acute Nephrosis (Treatment Adjunct)

Albumin (Human) 20% may be used to treat edema in patients with acute nephrosis who are refractory to cyclophosphamide and corticosteroid therapy. [1 ]

Hemolytic Disease of the Newborn (HDN)

Albumin (Human) 20% is indicated in the treatment of hyperbilirubinemia. It may be used prior to or during an exchange procedure in an attempt to bind free and to enhance its removal. [6 ]

Albumin (Human) 20% Dosage and Administration

Dosage

General Recommendations

The concentration of the albumin preparation, dosage and the infusion rate should be adjusted to the patient’s individual requirements.

The dose required depends on the body weight of the patient, the severity of trauma or illness and on continuing fluid and protein losses. Measures of adequacy of circulating volume and not plasma albumin levels should be used to determine the dose required.

The daily dose should not exceed 2 g of Albumin (Human) 20% per kg of body weight.

Hypovolemia

In adults, an intravenous infusion of 25 g should be given. If adequate response (stabilization of circulation) is not achieved within 15 to 30 minutes, an additional dose may be given.

In spite of limited information about the efficacy in pediatric subjects, an intravenous infusion of 2.5 to 12.5 g or 0.5 to 1 g/kg body weight may be given. If adequate response (stabilization of circulation) is not achieved within 15 to 30 minutes, an additional dose may be given.

Hemodilution may follow administration of Albumin (Human) 20%. If hemorrhage has occurred, this may result in relative anemia. This condition should be controlled by the supplemental administration of compatible red blood cells or compatible whole blood.

Hypoalbuminemia

In adults, intravenous infusion of 50 to 75 g of Albumin (Human) 20% may be used. Hypoalbuminemia is usually accompanied by a hidden extravascular albumin deficiency of equal magnitude. This total body albumin deficit must be considered when determining the amount of albumin necessary to reverse the hypoalbuminemia.

In burns, therapy usually starts with the administration of large volumes of crystalloid injection to maintain plasma volume. After 24 hours, Albumin (Human) 20% may be added at an initial dose of 25 g with the dose adjusted thereafter to maintain a plasma protein concentration of 2.5 g per 100 mL or a serum protein concentration of 5.2 g/100 mL.

Prevention of Central Volume Depletion after Paracentesis due to Cirrhotic Ascites

In adults, intravenous infusion of 8 g of Albumin (Human) 20% may be given for every 1,000 mL of ascitic fluid removed.

Ovarian Hyperstimulation Syndrome

In adults, as a guideline, doses of 50 – 100 g of Albumin (Human) 20% should be infused over 4 hours and repeated at 4- to 12-hour intervals as necessary, when infusion of normal saline fails to achieve or maintain hemodynamic stability and urine output. [7 ]

Adult Respiratory Distress Syndrome (ARDS)

In adults, a dose of 25 g of Albumin (Human) 20% can be infused over 30 minutes and repeated at 8 hour intervals for 3 days, if necessary. [5 ]

Induction of Diuresis in Patients with Acute Nephrosis

In adults, a dose of 25 g of Albumin (Human) 20% can be infused, administered with an appropriate diuretic once a day for 7 to 10 days.

Hemolytic Disease of the Newborn

In newborns, Albumin (Human) 20% may be administered prior to or during exchange transfusion at a dose of 1 g per kilogram body weight. [6 ]

Administration

Intravenous use only.

Prior to administration, parenteral drug products should be inspected visually for turbidity and discoloration, whenever solution and container permit.

Do not dilute with sterile water for injection.

Do not use solutions of Albumin (Human) 20% which are cloudy or have deposits. Once the infusion container has been opened the contents should be used immediately. Discard the unused portion. Filtration of Albumin (Human) 20% is not required.

The infusion rate should be adjusted according to the individual circumstances and the indication. In plasma exchange during paracentesis, the infusion rate may be higher and should be adjusted to the rate of removal.

If large volumes (greater than 1500 ml) are administered, the product should be warmed to room temperature before use.

Dosage Forms and Strengths

Albumin (Human) 20% is supplied in

• 10 g in 50 mL infusion bottle


• 20 g in 100 mL infusion bottle

Do not use in individuals who are hypersensitive to albumin preparations, any ingredient in the formulation, or components of the container.

Warnings and Precautions

Hypersensitivity

Hypersensitivity or allergic reactions have been observed, and may in some cases progress to severe anaphylaxis. Epinephrine should be available immediately to treat any acute hypersensitivity reaction.

Hypervolemia/Hemodilution

Hypervolemia may occur if the dosage and rate of infusion are not adjusted to the patient’s volume status. At the first clinical signs of possible cardiovascular overload, e.g., headache, dyspnea, increased blood pressure, jugular venous distention, elevated central venous pressure, pulmonary edema, the infusion should be stopped immediately and the patient reevaluated. Albumin should be used with caution in conditions where hypervolemia and its consequences or hemodilution could represent a special risk for the patient. Examples of such conditions are:

• Decompensated cardiac insufficiency


• Hypertension


• Esophageal varices


• Pulmonary edema


• Hemorrhagic diathesis


• Severe anemia


• Renal and post-renal anuria.

20-25% Albumin (Human) is relatively low in electrolytes compared to the 4-5% Albumin (Human) solutions. When albumin is given, monitor the electrolyte status of the patient and take appropriate steps to restore or maintain the electrolyte balance.

Coagulation Abnormalities

If comparatively large volumes are to be replaced, monitoring of coagulation and hematocrit is necessary. Ensure adequate substitution of other blood constituents (coagulation factors, electrolytes, platelets and erythrocytes).

Laboratory Monitoring

If Albumin (Human) 20% is to be administered, monitor hemodynamic performance regularly; this may include:

• Arterial blood pressure and pulse rate


• Central venous pressure


• Pulmonary artery occlusion pressure


• Urine output


• Electrolytes


• Hematocrit/hemoglobin.

Albumin (Human) 20% must not be diluted with sterile water for injection as this may cause hemolysis in recipients.

Infection Risk from Human Plasma

This product is a derivative of human plasma. 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 been identified for Albumin (Human) 20%.

Adverse Reactions

General

The most serious events are anaphylactic shock, circulatory failure, cardiac failure, and pulmonary edema.

The most common adverse events are anaphylactoid type of reactions.

Adverse reactions for Albumin (Human) 20% normally resolve when the infusion rate is slowed down or the infusion is stopped. In case of severe reactions, the infusion should be stopped and appropriate treatment should be initiated.

Clinical Studies Experience

No clinical studies were done using Albumin (Human) 20%

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of ALBUMIN (HUMAN) (any strength). Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency.

Table 1 Adverse reactions observed for ALBUMIN HUMAN (any strength) during post-marketing phase (in decreasing order of severity)

Observed Adverse Reactions
anaphylactic shock
cardiac failure
loss of consciousness
circulatory failure
hypersensitivity
congestive heart failure
pulmonary edema
dyspnea
hypotension
hypertension
tachycardia
bradycardia
vomiting
urticaria
angioneurotic edema
rash erythematous
confusional state
headache
chills
pyrexia
flushing
nausea
pruritus
hyperhidrosis

No drug interaction studies have been conducted.

Drug Interactions

No drug interaction studies have been conducted.

USE IN SPECIFIC POPULATIONS

Pregnancy

Pregnancy Category C. Animal reproduction studies have not been performed with Albumin (Human) 20%. It is also not known whether Albumin (Human) 20% can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Albumin (Human) 20% should be given to a pregnant woman only if necessary.

Labor and Delivery

It is also not known whether Albumin (Human) 20% can cause fetal harm when administered to a woman during labor or delivery of if it will affect reproductive capacity. Albumin (Human) 20% should be given during labor or delivery only if necessary.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Albumin (Human) 20% should be given to nursing mothers only if necessary. Because many drugs are excreted in human milk, caution should be exercised when Albumin (Human) 20% is administered to a lactating woman.

Pediatric Use

Data on the use of Albumin (Human) 20% in children including premature babies are very limited. The product should be administered to pediatric patients only if needed.

Geriatric Use

Clinical studies did not include a sufficient number of subjects aged 65 and older to determine whether they respond differently from younger subjects.

Albumin (Human) 20% Description

Albumin (Human) 20% is a sterile, liquid preparation of albumin derived from large pools of human plasma. All units of human plasma used in the manufacture of Albumin (Human) 20% are provided by FDA approved blood establishments only.

The product is manufactured by cold ethanol fractionation followed by ultra- and diafiltration. The manufacturing process includes final container pasteurization and additional bulk pasteurization at 60 +/- 0.5°C for 10 – 11 hours. The Albumin (Human) 20% manufacturing process provides a significant viral reduction in in vitro studies (table 2). These reductions are achieved through a combination of process steps including Cohn fractionation and final container pasteurization.

No procedure, however, has been shown to be completely effective in removing viral infectivity from derivatives of human plasma.[see Warnings and Precautions, Infection Risk from Human Plasma (5.7)]

Table 2 In vitro reduction factor during Albumin (Human) 20% manufacturing

PRV:Pseudorabies Virus

SBV: Sindbis Virus

HIV-1:Human Immunodeficiency Virus - 1

Reo 3:Reovirus Type 3

PPV:Porcine Parvovirus

HAV:Hepatitis A Virus

Albumin (Human) 20% is a clear, slightly viscous liquid; it is almost colorless or slightly yellow or green.

The composition of Albumin (Human) 20% is as follows:

Component		Quantity/1000 ml
Protein, of which greater than or equal to
96% is human albumin		200 g
Sodium		130 – 160 mmol
Potassium		less than or equal to 2 mmol
N-acetyl-DL-tryptophan		0.064 - 0.096 mmol/g protein
Caprylic acid		0.064 - 0.096 mmol/g protein
Water for Injection		ad. 1000 ml

Albumin (Human) 20% contains no preservatives and components used in its packaging are latex-free.

Albumin (Human) 20% - Clinical Pharmacology

No pharmacokinetic or pharmacodynamic studies with Albumin (Human) 20% have been conducted.

Mechanism of Action

Albumin is responsible for 75-80% of the colloid osmotic pressure of normal plasma. Albumin stabilizes circulating blood volume and is a carrier of hormones, enzymes, medicinal products and toxins. [3 ]

Albumin is a protein with a total extravascular mass of approximately 160 g and an intravascular mass of about 120 g. [3 ]

Pharmacodynamics

The colloid osmotic effect of Albumin (Human) 20% and 25% is approximately 5 times the volume administered. When injected intravenously, it will increase circulating plasma volume by approximately 3.5 times the volume infused within 15 minutes if the patient is adequately hydrated. This extra fluid reduces hemoconcentration and blood viscosity. The degree and duration of volume expansion depends upon the initial blood volume. When treating patients with diminished blood volume, the effect of infused albumin may persist for many hours. The hemodilution lasts for a shorter time when albumin is administered to individuals with normal blood volume. [4 ]

NON-CLINICAL TOXICOLOGY

No non-clinical toxicology studies with Albumin (Human) 20% have been conducted. Human Albumin is a normal constituent of human plasma and acts like physiological albumin.

Clinical Studies

No clinical studies with Albumin (Human) 20% have been conducted.

REFERENCES

1. Tullis JL: Albumin 2.Guidelines for Clinical Use. JAMA 1977; 237:460-463


2. Vermeulen LC et al.: A Paradigm for Consensus. Arch. Intern. Med. 1995; 155:373-379


3. Mendez CM, McClain CJ, Marsano LS: Albumin Therapy in Clinical Practice. Nutrition in Clinical Practice 2005; 20: 314-320


4. Janeway, C. A. "Human Serum Albumin: Historical Review" in: Proceedings of the Workshop on Albumin. DHEW Publication No. (NIH) 76-925. Sgouris, J. T. and René A. (eds.), Washington, D.C., U.S. Government Printing Office. 1976, pp 3-21.


5. Martin GS et al.: A randomized, controlled trail of furosemide with or without albumin in hypoproteinemic patients with acute lung injury. Crit. Care Med. 2005; 33: 1681-1687


6. Tsao YC, Yu VY: Albumin in management of neonatal hyperbilirubinaemia. Arch Dis.Child 1972;47:250-256.


7. Practice Committee of the American Society for Reproductive Medicine. Ovarian hyperstimulation syndrome. Fertil.Steril. 2006;86:S178-S183.


8. Aboulghar M, Evers JH, Al Inany H: Intravenous albumin for preventing severe ovarian hyperstimulation syndrome: a Cochrane review. Hum.Reprod. 2002;17:3027-3032.

How Supplied/Storage and Handling

Albumin (Human) 20% is supplied in 10 g in 50 mL or 20 g in 100 mL single use bottles.

NDC Number	NDC Number	Size	Grams protein
Octapharma Pharmazeutika Produktionsges.m.b.H	Octapharma AB
67467-633-01	68209-633-01	50 ml	10
67467-633-02	68209-633-02	100 ml	20

Albumin (Human) 20% may be stored for 36 months at +2°C to + 25°C (36°F to 77°F) from the date of manufacture.

Store protected from light.

Do not freeze.

Do not use after expiration date.

Do not use if turbid.

Patient Counseling Information

Information for Patients

This product is usually given in a hospital setting.

Inform patients being treated with Albumin (Human) 20% about the potential risks and benefits with its use [see Adverse Reactions (6)].

Discontinue immediately if allergic symptoms occur (e.g. skin rashes, hives, itching, breathing difficulties, coughing, nausea, vomiting, fall in blood pressure, increased heart rate).

Inform patients that Albumin (Human) 20% is a derivative of human plasma and may contain infectious agents that cause disease (e.g., viruses, and theoretically, CJD agent). Inform patients that the risk that Albumin (Human) 20% may transmit an infections agent has been reduced by screening plasma donors for prior exposure for certain viruses, by testing the donated plasma for certain virus infections and by inactivating and/or removing certain viruses during manufacturing [see Warnings and Precautions (5.7)].

Manufactured by:

Octapharma Pharmazeutika Produktionsges.m.b.H.

Oberlaaer Strasse 235

A-1100 Vienna, Austria

Octapharma AB

Elersvägen 40

SE- 112 75, Sweden

U.S. License No. 1646

Distributed by:

Octapharma USA Inc.

121 River Street, 12 th floor

Hoboken, NJ 07030

PACKAGE LABEL - PRINCIPAL DISPLAY PANEL

Albumin (Human) 20%

10 g in 50 mL

Octapharma Pharmazeutika Produktionsges.m.b.H

NDC 67467-633-01

Octapharma AB

NDC 68209-633-01

Albumin (Human) 20%

20 g in 100 mL

Octapharma Pharmazeutika Produktionsges.m.b.H

NDC 67467-633-02

Octapharma AB

NDC 68209-633-02

ALBUMIN (HUMAN)  albumin human  solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 67467-633 Route of Administration Intravenous DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ALBUMIN (HUMAN) (ALBUMIN (HUMAN)) ALBUMIN (HUMAN) 200 g  in 1000 mL

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 67467-633-01 50 mL In 1 BOTTLE, GLASS None 2 67467-633-02 100 mL In 1 BOTTLE, GLASS None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
BLA	BLA125154	10/17/2006

Labeler - Octapharma Pharmazeutika Produktionsgesellschaft m.b.H. (301119178)

Revised: 01/2010Octapharma Pharmazeutika Produktionsgesellschaft m.b.H.

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Gabapentin 100 mg Capsules (Sandoz Limited )

1. Name Of The Medicinal Product

Gabapentin 100 mg Capsules

2. Qualitative And Quantitative Composition

Each capsule, hard contains 100 mg of gabapentin.

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Capsule, hard

Hard gelatin capsule (size 3), with white opaque body and cap.

4. Clinical Particulars

4.1 Therapeutic Indications

Epilepsy

Gabapentin is indicated as adjunctive therapy in the treatment of partial seizures with and without secondary generalization in adults and children aged 6 years and above (see section 5.1).

Gabapentin is indicated as monotherapy in the treatment of partial seizures with and without secondary generalization in adults and adolescents aged 12 years and above.

Treatment of peripheral neuropathic pain

Gabapentin is indicated for the treatment of peripheral neuropathic pain such as painful diabetic neuropathy and post-herpetic neuralgia in adults.

4.2 Posology And Method Of Administration

For oral use.

Gabapentin can be given with or without food and should be swallowed whole with sufficient fluid-intake (e.g. a glass of water).

For all indications a titration scheme for the initiation of therapy is described in Table 1, which is recommended for adults and adolescents aged 12 years and above. Dosing instructions for children under 12 years of age are provided under a separate sub-heading later in this section.

Table 1
DOSING CHART – INITIAL TITRATION
Day 1	Day 2	Day 3
300 mg once a day	300 mg two times a day	300 mg three times a day

Epilepsy

Epilepsy typically requires long-term therapy. Dosage is determined by the treating physician according to individual tolerance and efficacy. When in the judgment of the clinician there is a need for dose reduction, discontinuation, or substitution with an alternative medication, this should be done gradually over a minimum of one week.

Adults and adolescents:

In clinical trials, the effective dosing range was 900 to 3600 mg/day. Therapy may be initiated by titrating the dose as described in Table 1 or by administering 300 mg three times a day (TID) on Day 1. Thereafter, based on individual patient response and tolerability, the dose can be further increased in 300 mg/day increments every 2-3 days up to a maximum dose of 3600 mg/day. Slower titration of gabapentin dosage may be appropriate for individual patients. The minimum time to reach a dose of 1800 mg/day is one week, to reach 2400 mg/day is a total of 2 weeks, and to reach 3600 mg/day is a total of 3 weeks. Dosages up to 4800 mg/day have been well tolerated in long-term open-label clinical studies. The total daily dose should be divided in three single doses, the maximum time interval between the doses should not exceed 12 hours to prevent breakthrough convulsions.

Children aged 6 years and above:

The starting dose should range from 10 to 15 mg/kg/day and the effective dose is reached by upward titration over a period of approximately three days. The effective dose of gabapentin in children aged 6 years and older is 25 to 35 mg/kg/day. Dosages up to 50 mg/kg/day have been well tolerated in a long-term clinical study. The total daily dose should be divided in three single doses, the maximum time interval between doses should not exceed 12 hours.

It is not necessary to monitor gabapentin plasma concentrations to optimize gabapentin therapy. Further, gabapentin may be used in combination with other antiepileptic medicinal products without concern for alteration of the plasma concentrations of gabapentin or serum concentrations of other antiepileptic medicinal products.

Peripheral neuropathic pain

Adults

The therapy may be initiated by titrating the dose as described in Table 1. Alternatively, the starting dose is 900 mg/day given as three equally divided doses. Thereafter, based on individual patient response and tolerability, the dose can be further increased in 300 mg/day increments every 2-3 days up to a maximum dose of 3600 mg/day. Slower titration of gabapentin dosage may be appropriate for individual patients. The minimum time to reach a dose of 1800 mg/day is one week, to reach 2400 mg/day is a total of 2 weeks, and to reach 3600 mg/day is a total of 3 weeks.

In the treatment of peripheral neuropathic pain such as painful diabetic neuropathy and post-herpetic neuralgia, efficacy and safety have not been examined in clinical studies for treatment periods longer than 5 months. If a patient requires dosing longer than 5 months for the treatment of peripheral neuropathic pain, the treating physician should assess the patient's clinical status and determine the need for additional therapy.

Instruction for all areas of indication

In patients with poor general health, i.e., low body weight, after organ transplantation etc., the dose should be titrated more slowly, either by using smaller dosage strengths or longer intervals between dosage increases.

Use in elderly patients (over 65 years of age)

Elderly patients may require dosage adjustment because of declining renal function with age (see Table 2). Somnolence, peripheral oedema and asthenia may be more frequent in elderly patients.

Use in patients with renal impairment

Dosage adjustment is recommended in patients with compromised renal function as described in Table 2 and/or those undergoing haemodialysis. Gabapentin 100 mg capsules can be used to follow dosing recommendations for patients with renal insufficiency.

Table 2
Dosage of Gabapentin in Adults Based on Renal Function
Creatinine Clearance (ml/min)	Total Daily Dosea (mg/day)
	900-3600
50-79	600-1800
30-49	300-900
15-29	150b-600
<15c	150b-300

^a Total daily dose should be administered as three divided doses. Reduced dosages are for patients with renal impairment (creatinine clearance < 79 ml/min).

^b To be administered as 300 mg every other day.

^c For patients with creatinine clearance <15 ml/min, the daily dose should be reduced in proportion to creatinine clearance (e.g., patients with a creatinine clearance of 7.5 ml/min should receive one-half the daily dose that patients with a creatinine clearance of 15 ml/min receive).

Use in patients undergoing haemodialysis

For anuric patients undergoing haemodialysis who have never received gabapentin, a loading dose of 300 to 400 mg, then 200 to 300 mg of gabapentin following each 4 hours of haemodialysis, is recommended. On dialysis-free days, there should be no treatment with gabapentin.

For renally impaired patients undergoing haemodialysis, the maintenance dose of gabapentin should be based on the dosing recommendations found in Table 2. In addition to the maintenance dose, an additional 200 to 300 mg dose following each 4-hour haemodialysis treatment is recommended.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients.

4.4 Special Warnings And Precautions For Use

If a patient develops acute pancreatitis under treatment with gabapentin, iscontinuation of gabapentin should be considered (see section 4.8).

Although there is no evidence of rebound seizures with gabapentin, abrupt withdrawal of anticonvulsants in epileptic patients may precipitate status epilepticus (see section 4.2).

As with other antiepileptic medicinal products, some patients may experience an increase in seizure frequency or the onset of new types of seizures with gabapentin.

As with other anti-epileptics, attempts to withdraw concomitant anti-epileptics in treatment refractory patients on more than one anti-epileptic, in order to reach gabapentin monotherapy have a low success rate.

Gabapentin is not considered effective against primary generalized seizures such as absences and may aggravate these seizures in some patients. Therefore, gabapentin should be used with caution in patients with mixed seizures including absences.

No systematic studies in patients 65 years or older have been conducted with gabapentin. In one double blind study in patients with neuropathic pain, somnolence, peripheral oedema and asthenia occurred in a somewhat higher percentage in patients aged 65 years or above, than in younger patients. Apart from these findings, clinical investigations in this age group do not indicate an adverse event profile different from that observed in younger patients.

The effects of long-term (greater than 36 weeks) gabapentin therapy on learning, intelligence, and development in children and adolescents have not been adequately studied. The benefits of prolonged therapy must therefore be weighed against the potential risks of such therapy.

Suicidal ideation and behaviour have been reported in patients treated with antiepileptic agents in several indications. A meta-analysis of randomised placebo controlled trials of anti-epileptic drugs has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for gabapentin. Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.

Laboratory tests

False positive readings may be obtained in the semi-quantitative determination of total urine protein by dipstick tests. It is therefore recommended to verify such a positive dipstick test result by methods based on a different analytical principle such as the Biuret method, turbidimetric or dye-binding methods, or to use these alternative methods from the beginning.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

In a study involving healthy volunteers (N=12), when a 60 mg controlled-release morphine capsule was administered 2 hours prior to a 600 mg gabapentin capsule, mean gabapentin AUC increased by 44% compared to gabapentin administered without morphine. Therefore, patients should be carefully observed for signs of CNS depression, such as somnolence, and the dose of gabapentin or morphine should be reduced appropriately.

No interaction between gabapentin and phenobarbital, phenytoin, valproic acid, or carbamazepine has been observed.

Gabapentin steady-state pharmacokinetics are similar for healthy subjects and patients with epilepsy receiving these antiepileptic agents.

Coadministration of gabapentin with oral contraceptives containing norethindrone and/or ethinyl estradiol, does not influence the steady-state pharmacokinetics of either component.

Coadministration of gabapentin with antacids containing aluminium and magnesium, reduces gabapentin bioavailability up to 24%. It is recommended that gabapentin be taken at the earliest two hours following antacid administration.

Renal excretion of gabapentin is unaltered by probenecid.

A slight decrease in renal excretion of gabapentin that is observed when it is coadministered with cimetidine is not expected to be of clinical importance.

4.6 Pregnancy And Lactation

Risk related to epilepsy and antiepileptic medicinal products in general

The risk of birth defects is increased by a factor of 2 – 3 in the offspring of mothers treated with an antiepileptic medicinal product. Most frequently reported are cleft lip, cardiovascular malformations and neural tube defects. Multiple antiepileptic drug therapy may be associated with a higher risk of congenital malformations than monotherapy, therefore it is important that monotherapy is practised whenever possible. Specialist advice should be given to women who are likely to become pregnant or who are of childbearing potential and the need for antiepileptic treatment should be reviewed when a woman is planning to become pregnant. No sudden discontinuation of antiepileptic therapy should be undertaken as this may lead to breakthrough seizures, which could have serious consequences for both mother and child. Developmental delay in children of mothers with epilepsy has been observed rarely. It is not possible to differentiate if the developmental delay is caused by genetic, social factors, maternal epilepsy or the antiepileptic therapy.

Risk related to gabapentin

There are no adequate data from the use of gabapentin in pregnant women.

Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Gabapentin should not be used during pregnancy unless the potential benefit to the mother clearly outweighs the potential risk to the foetus.

No definite conclusion can be made as to whether gabapentin is associated with an increased risk of congenital malformations when taken during pregnancy, because of epilepsy itself and the presence of concomitant antiepileptic medicinal products during each reported pregnancy.

Gabapentin is excreted in human milk. Because the effect on the breast-fed infant is unknown, caution should be exercised when gabapentin is administered to a breast-feeding mother. Gabapentin should be used in breast-feeding mothers only if the benefits clearly outweigh the risks.

4.7 Effects On Ability To Drive And Use Machines

Gabapentin may have minor or moderate influence on the ability to drive and use machines. Gabapentin acts on the central nervous system and may cause drowsiness, dizziness or other related symptoms. Even, if they were only of mild or moderate degree, these undesirable effects could be potentially dangerous in patients driving or operating machinery. This is especially true at the beginning of the treatment and after increase in dose.

4.8 Undesirable Effects

The adverse reactions observed during clinical studies conducted in epilepsy (adjunctive and monotherapy) and neuropathic pain have been provided in a single list below by class and frequency (very common (

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Infections and infestations
Very Common:	Viral infection
Common:	Pneumonia, respiratory infection, urinary tract infection, infection, otitis media
Blood and the lymphatic system disorders
Common:	Leucopenia
Rare:	Thrombocytopenia
Immune system disorders
Rare:	Allergic reactions (e.g. urticaria)
Metabolism and Nutrition Disorders
Common:	Anorexia, increased appetite
Psychiatric disorders
Common:	Hostility, confusion and emotional lability, depression, anxiety, nervousness, thinking abnormal
Rare:	Hallucinations
Nervous system disorders
Very Common:	Somnolence, dizziness, ataxia,
Common:	Convulsions, hyperkinesias, dysarthria, amnesia, tremor, insomnia, headache, sensations such as paresthesia, hypaesthesia, coordination abnormal, nystagmus, increased, decreased, or absent reflexes
Rare:	Movement disorders (e.g. choreoathetosis, dyskinesia, dystonia)
Eye disorders
Common:	Visual disturbances such as amblyopia, diplopia
Ear and Labyrinth disorders
Common:	Vertigo
Rare:	Tinnitus
Cardiac disorders
Rare:	Palpitations
Vascular disorder
Common:	Hypertension, vasodilatation
Respiratory, thoracic and mediastinal disorders
Common:	Dyspnoea, bronchitis, pharyngitis, cough, rhinitis
Gastrointestinal disorders
Common:	Vomiting, nausea, dental abnormalities, gingivitis, diarrhea, abdominal pain, dyspepsia, constipation, dry mouth or throat, flatulence
Rare:	Pancreatitis
Hepatobiliary disorders
Rare:	Hepatitis, jaundice
Skin and subcutaneous tissue disorders
Common:	Facial oedema, purpura most often described as bruises resulting from physical trauma, rash, pruritus, acne
Rare:	Stevens-Johnson syndrome, angioedema, erythema multiforme, alopecia
Musculoskeletal, connective tissue and bone disorders
Common:	Arthralgia, myalgia, back pain, twitching
Renal and urinary disorders
Common:	Incontinence
Rare:	Acute renal failure
Reproductive system and breast disorders
Common:	Impotence
General disorders and administration site conditions
Very Common:	Fatigue, fever
Common:	Peripheral or generalized oedema, abnormal gait, asthenia, pain, malaise, flu syndrome
Rare:	Withdrawal reactions (mostly anxiety, insomnia, nausea, pains, sweating), chest pain. Sudden unexplained deaths have been reported where a causal relationship to treatment with gabapentin has not been established.
Investigations
Common:	WBC (white blood cell count) decreased, weight gain
Rare:	Blood glucose fluctuations in patients with diabetes, elevated liver function tests
Injury and poisoning
Common:	Accidental injury, fracture, abrasion

Under treatment with gabapentin cases of acute pancreatitis were reported. Causality with gabapentin is unclear (see section 4.4).

Respiratory tract infections, otitis media, convulsions and bronchitis were reported only in clinical studies in children. Additionally, in clinical studies in children, aggressive behaviour and hyperkinesias were reported commonly.

4.9 Overdose

Acute, life-threatening toxicity has not been observed with gabapentin overdoses of up to 49 g. Symptoms of the overdoses included dizziness, double vision, slurred speech, drowsiness, lethargy and mild diarrhoea. All patients recovered fully with supportive care. Reduced absorption of gabapentin at higher doses may limit drug absorption at the time of overdosing and, hence, minimize toxicity from overdoses.

Although gabapentin can be removed by haemodialysis, based on prior experience it is usually not required. However, in patients with severe renal impairment, haemodialysis may be indicated.

An oral lethal dose of gabapentin was not identified in mice and rats given doses as high as 8000 mg/kg. Signs of acute toxicity in animals included ataxia, laboured breathing, ptosis, hypoactivity, or excitation.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic groups: Other antiepileptics ATC code: N03AX12

The precise mechanism of action of gabapentin is not known.

Gabapentin is structurally related to the neurotransmitter GABA (gamma-aminobutyric acid) but its mechanism of action is different from that of several other active substances that interact with GABA synapses including valproate, barbiturates, benzodiazepines, GABA transaminase inhibitors, GABA uptake inhibitors, GABA agonists, and GABA prodrugs. In vitro studies with radiolabeled gabapentin have characterized a novel peptide binding site in rat brain tissues including neocortex and hippocampus that may relate to anticonvulsant and analgesic activity of gabapentin and its structural derivatives. The binding site for gabapentin has been identified as the alpha2-delta subunit of voltage-gated calcium channels.

Gabapentin at relevant clinical concentrations does not bind to other common drug or neurotransmitter receptors of the brain including GABAA, GABAB, benzodiazepine, glutamate, glycine or N-methyl-d-aspartate receptors.

Gabapentin does not interact with sodium channels in vitro and so differs from phenytoin and carbamazepine. Gabapentin partially reduces responses to the glutamate agonist N-methyl-D-aspartate (NMDA) in some test systems in vitro, but only at concentrations greater than 100 µM, which are not achieved in vivo. Gabapentin slightly reduces the release of monoamine neurotransmitters in vitro. Gabapentin administration to rats increases GABA turnover in several brain regions in a manner similar to valproate sodium, although in different regions of brain. The relevance of these various actions of gabapentin to the anticonvulsant effects remains to be established. In animals, gabapentin readily enters the brain and prevents seizures from maximal electroshock, from chemical convulsants including inhibitors of GABA synthesis, and in genetic models of seizures.

A clinical trial of adjunctive treatment of partial seizures in paediatric subjects, ranging in age from 3 to 12 years, showed a numerical but not statistically significant difference in the 50% responder rate in favour of the gabapentin group compared to placebo. Additional post-hoc analyses of the responder rates by age did not reveal a statistically significant effect of age, either as a continuous or dichotomous variable (age groups 3-5 and 6-12 years). The data from this additional post-hoc analysis are summarised in the table below:

Response (
Age Category	Placebo	Gabapentin	P-Value
< 6 Years Old	4/21 (19.0%)	4/17 (23.5%)	0.7362
6 to 12 Years Old	17/99 (17.2%)	20/96 (20.8%)	0.5144

*The modified intent to treat population was defined as all patients randomised to study medication who also had evaluable seizure diaries available for 28 days during both the baseline and double-blind phases.

5.2 Pharmacokinetic Properties

Absorption

Following oral administration, peak plasma gabapentin concentrations are observed within 2 to 3 hours. Gabapentin bioavailability (fraction of dose absorbed) tends to decrease with increasing dose. Absolute bioavailability of a 300 mg capsule is approximately 60%. Food, including a high-fat diet, has no clinically significant effect on gabapentin pharmacokinetics.

Gabapentin pharmacokinetics are not affected by repeated administration. Although plasma gabapentin concentrations were generally between 2 µg/ml and 20 µg/ml in clinical studies, such concentrations were not predictive of safety or efficacy. Pharmacokinetic parameters are given in Table 3.

Table 3

Summary of gabapentin mean (%CV) steady-state pharmacokinetic parameters following every eight hours administration

Pharmacokinetic parameter	300 mg (N = 7)	400 mg (N = 14)	800 mg (N=14)
	Mean	%CV	Mean	%CV	Mean	%CV
Cmax (μg/ml)	4.02	(24)	5.74	(38)	8.71	(29)
tmax (hr)	2.7	(18)	2.1	(54)	1.6	(76)
T1/2 (hr)	5.2	(12)	10.8	(89)	10.6	(41)
AUC (0-8) μg•hr/ml)	24.8	(24)	34.5	(34)	51.4	(27)
Ae% (%)	NA	NA	47.2	(25)	34.4	(37)
Cmax = Maximum steady state plasma concentration tmax = Time for Cmax T1/2 = Elimination half-life AUC(0-8) = Steady state area under plasma concentration-time curve from time 0 to 8 hours postdose Ae% = Percent of dose excreted unchanged into the urine from time 0 to 8 hours postdose NA = Not available

Distribution

Gabapentin is not bound to plasma proteins and has a volume of distribution equal to 57.7 litres. In patients with epilepsy, gabapentin concentrations in cerebrospinal fluid (CSF) are approximately 20% of corresponding steady-state trough plasma concentrations. Gabapentin is present in the breast milk of breast-feeding women.

Metabolism

There is no evidence of gabapentin metabolism in humans. Gabapentin does not induce hepatic mixed function oxidase enzymes responsible for drug metabolism.

Elimination

Gabapentin is eliminated unchanged solely by renal excretion. The elimination half-life of gabapentin is independent of dose and averages 5 to 7 hours.

In elderly patients, and in patients with impaired renal function, gabapentin plasma clearance is reduced. Gabapentin elimination-rate constant, plasma clearance, and renal clearance are directly proportional to creatinine clearance.

Gabapentin is removed from plasma by haemodialysis. Dosage adjustment in patients with compromised renal function or undergoing haemodialysis is recommended (see section 4.2).

Gabapentin pharmacokinetics in children were determined in 50 healthy subjects between the ages of 1 month and 12 years. In general, plasma gabapentin concentrations in children > 5 years of age are similar to those in adults when dosed on a mg/kg basis.

Linearity/Non-linearity

Gabapentin bioavailability (fraction of dose absorbed) decreases with increasing dose which imparts non-linearity to pharmacokinetic parameters which include the bioavailability parameter (F) e.g. Ae%, CL/F, Vd/F. Elimination pharmacokinetics (pharmacokinetic parameters which do not include F such as CLr and T1/2), are best described by linear pharmacokinetics. Steady state plasma gabapentin concentrations are predictable from single-dose data.

5.3 Preclinical Safety Data

Carcinogenesis

Gabapentin was given in the diet to mice at 200, 600, and 2000 mg/kg/day and to rats at 250, 1000, and 2000 mg/kg/day for two years. A statistically significant increase in the incidence of pancreatic acinar cell tumors was found only in male rats at the highest dose. Peak plasma drug concentrations in rats at 2000 mg/kg/day are 10 times higher than plasma concentrations in humans given 3600 mg/day. The pancreatic acinar cell tumors in male rats are low-grade malignancies, did not affect survival, did not metastasize or invade surrounding tissue, and were similar to those seen in concurrent controls. The relevance of these pancreatic acinar cell tumors in male rats to carcinogenic risk in humans is unclear.

Mutagenesis

Gabapentin demonstrated no genotoxic potential. It was not mutagenic in vitro in standard assays using bacterial or mammalian cells. Gabapentin did not induce structural chromosome aberrations in mammalian cells in vitro or in vivo, and did not induce micronucleus formation in the bone marrow of hamsters.

Impairment of Fertility

No adverse effects on fertility or reproduction were observed in rats at doses up to 2000 mg/kg (approximately five times the maximum daily human dose on a mg/m2 of body surface area basis).

Teratogenesis

Gabapentin did not increase the incidence of malformations, compared to controls, in the offspring of mice, rats, or rabbits at doses up to 50, 30 and 25 times respectively, the daily human dose of 3600 mg, (four, five or eight times, respectively, the human daily dose on a mg/m2 basis).

Gabapentin induced delayed ossification in the skull, vertebrae, forelimbs, and hindlimbs in rodents, indicative of fetal growth retardation. These effects occurred when pregnant mice received oral doses of 1000 or 3000 mg/kg/day during organogenesis and in rats given 500, 1000, or 2000 mg/kg prior to and during mating and throughout gestation. These doses are approximately 1 to 5 times the human dose of 3600 mg on a mg/m2 basis.

No effects were observed in pregnant mice given 500 mg/kg/day (approximately 1/2 of the daily human dose on a mg/m2 basis).

An increased incidence of hydroureter and/or hydronephrosis was observed in rats given 2000 mg/kg/day in a fertility and general reproduction study, 1500 mg/kg/day in a teratology study, and 500, 1000, and 2000 mg/kg/day in a perinatal and postnatal study. The significance of these findings is unknown, but they have been associated with delayed development. These doses are also approximately 1 to 5 times the human dose of 3600 mg on a mg/m2 basis.

In a teratology study in rabbits, an increased incidence of post-implantation fetal loss, occurred in doses given 60, 300, and 1500 mg/kg/day during organogenesis. These doses are approximately 1/4 to 8 times the daily human dose of 3600 mg on a mg/m2 basis.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Capsule content:

Maize starch, pregelatinised

Maize starch

Talc

Silica, colloidal anhydrous

Capsule shell:

Gelatin

Sodium laurel sulphate

Titanium dioxide (E171)

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

36 months

6.4 Special Precautions For Storage

Store below 25°C.

Blisters: Store in the original package in order to protect from moisture.

Tablet containers: Keep the tablet container tightly closed in order to protect from moisture.

6.5 Nature And Contents Of Container

PVC/PE/PVDC//Alu blister

HDPE tablet container with PP (Polypropylene) child resistant closure.

Pack sizes:

Blister: 7, 15, 20, 30, 50, 60, 90, 100 and 200 capsules, hard

Tablet container : 50, 100 capsules, hard.

Not all pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

No special requirements.

7. Marketing Authorisation Holder

Sandoz Ltd

Frimley Business Park,

Frimley,

Camberley,

Surrey,

GU16 7SR.

United Kingdom

8. Marketing Authorisation Number(S)

PL 04416/1052

9. Date Of First Authorisation/Renewal Of The Authorisation

16/02/2009

10. Date Of Revision Of The Text

11/2010

Dexall

Generic Name: dexbrompheniramine, dextromethorphan, and phenylephrine (dex brom feh NEER a meen, dex tro meh THOR fan, and feh nill EFF rin)

Brand Names: Dexall, Tussall, Tussall-ER, Y-Cof DM

What is Dexall (dexbrompheniramine, dextromethorphan, and phenylephrine)?

Dexbrompheniramine is an antihistamine that reduces the effects of the natural chemical histamine in the body. Histamine can produce symptoms of sneezing, itching, watery eyes, and runny nose.

Dextromethorphan is a cough suppressant. It affects the signals in the brain that trigger cough reflex.

Phenylephrine is a decongestant that shrinks blood vessels in the nasal passages. Dilated blood vessels can cause nasal congestion (stuffy nose).

The combination of dexbrompheniramine, dextromethorphan, and phenylephrine is used to treat runny or stuffy nose, sneezing, itching, watery eyes, cough, and sinus congestion caused by allergies, the common cold, or the flu.

This medicine will not treat a cough that is caused by smoking, asthma, or emphysema.

Dexbrompheniramine, dextromethorphan, and phenylephrine may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Dexall (dexbrompheniramine, dextromethorphan, and phenylephrine)?

Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children. You should not use this medication if you have severe constipation, a blockage in your stomach or intestines, or if you are unable to urinate. Do not use cough or cold medicine if you have untreated or uncontrolled diseases such as glaucoma, asthma or COPD, high blood pressure, heart disease, coronary artery disease, or overactive thyroid. Do not use cough or cold medicine if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days. A dangerous drug interaction could occur, leading to serious side effects.

What should I discuss with my healthcare provider before taking Dexall (dexbrompheniramine, dextromethorphan, and phenylephrine)?

Do not use cough or cold medicine if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days. A dangerous drug interaction could occur, leading to serious side effects. You should not use this medication if you have severe constipation, a blockage in your stomach or intestines, or if you are unable to urinate. Do not use cough or cold medicine if you have untreated or uncontrolled diseases such as glaucoma, asthma or COPD, high blood pressure, heart disease, coronary artery disease, or overactive thyroid.

Ask a doctor or pharmacist if it is safe for you to take this medication if you have:

• 
  

  a blockage in your digestive tract (stomach or intestines), a colostomy or ileostomy;

  
  


• 
  

  diabetes;

  
  


• 
  

  liver or kidney disease;

  
  


• 
  

  epilepsy or other seizure disorder;

  
  


• 
  

  cough with mucus, or cough caused by emphysema or chronic bronchitis;

  
  


• 
  

  enlarged prostate or urination problems;

  
  


• 
  

  low blood pressure;

  
  


• 
  

  pheochromocytoma (an adrenal gland tumor); or

  
  


• 
  

  if you take potassium (Cytra, Epiklor, K-Lyte, K-Phos, Kaon, Klor-Con, Polycitra, Urocit-K).

  
  

FDA pregnancy category C. It is not known whether this medication will harm an unborn baby. Do not use cough or cold medicine without medical advice if you are pregnant. This medicine may pass into breast milk and may harm a nursing baby. Antihistamines and decongestants may also slow breast milk production. Do not use cough or cold medicine without medical advice if you are breast-feeding a baby.

How should I take Dexall (dexbrompheniramine, dextromethorphan, and phenylephrine)?

Use exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Cough or cold medicine is usually taken only for a short time until your symptoms clear up.

Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children.

Do not take for longer than 7 days in a row. Talk with your doctor if your symptoms do not improve after 7 days of treatment, or if you have a fever with a headache or skin rash.

Measure liquid medicine with a special dose-measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

Do not crush, chew, break, or open an extended-release tablet. Swallow it whole. Breaking the pill may cause too much of the drug to be released at one time. If you need surgery or medical tests, tell the surgeon or doctor ahead of time if you have taken a cough or cold medicine within the past few days. Store at room temperature away from moisture and heat. Do not freeze.

What happens if I miss a dose?

Since cough or cold medicine is taken when needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

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

Overdose symptoms may include severe forms of some of the side effects listed in this medication guide.

What should I avoid while taking Dexall (dexbrompheniramine, dextromethorphan, and phenylephrine)?

This medicine may cause blurred vision and may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert and able to see clearly. Drinking alcohol can increase certain side effects of this medication. Ask a doctor or pharmacist before using any other cold, allergy, cough, or sleep medicine. Antihistamines, cough suppressants, and decongestants are contained in many combination medicines. Taking certain products together can cause you to get too much of a certain drug. Check the label to see if a medicine contains an antihistamine, cough suppressant, or decongestant.

Avoid taking this medication if you also take diet pills, caffeine pills, or other stimulants (such as ADHD medications). Taking a stimulant together with a decongestant can increase your risk of unpleasant side effects.

Avoid becoming overheated or dehydrated during exercise and in hot weather. This medication can decrease sweating and you may be more prone to heat stroke.

Dexall (dexbrompheniramine, dextromethorphan, and phenylephrine) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat. Stop using this medicine and call your doctor at once if you have a serious side effect such as:

• 
  

  fast, slow, or uneven heart rate;

  
  


• 
  

  severe headache, mood changes, hallucinations;

  
  


• 
  

  severe dizziness or anxiety, feeling like you might pass out;

  
  


• 
  

  tremor, seizure (convulsions);

  
  


• 
  

  easy bruising or bleeding, unusual weakness;

  
  


• 
  

  fever;

  
  


• 
  

  urinating less than usual or not at all;

  
  


• 
  

  feeling short of breath; or

  
  


• 
  

  dangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, anxiety, confusion, chest pain, uneven heartbeats, seizure).

  
  

Less serious side effects may include:

• 
  

  mild headache;

  
  


• 
  

  mild dizziness, drowsiness;

  
  


• 
  

  dry mouth, nose, or throat;

  
  


• 
  

  nausea, diarrhea, constipation, upset stomach;

  
  


• 
  

  feeling nervous, restless, or irritable;

  
  


• 
  

  blurred vision; or

  
  


• 
  

  sleep problems (insomnia).

  
  

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Dexall (dexbrompheniramine, dextromethorphan, and phenylephrine)?

Ask a doctor or pharmacist before using this medicine if you regularly use other medicines that make you sleepy (such as narcotic pain medication, sedatives, sleeping pills, muscle relaxers, and medicine for seizures, depression or anxiety). They can add to sleepiness caused by dexbrompheniramine or dextromethorphan.

Ask a doctor or pharmacist if it is safe for you to take this medication if you are also using any of the following drugs:

• 
  

  atropine (Atreza, Sal-Tropine);

  
  


• 
  

  benztropine (Cogentin);

  
  


• 
  

  topiramate (Topamax);

  
  


• 
  

  zonisamide (Zonegran);

  
  


• 
  

  an antidepressant such as citalopram (Celexa), duloxetine (Cymbalta), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, Symbyax), paroxetine (Paxil, Pexeva), sertraline (Zoloft), venlafaxine (Effexor), and others;

  
  


• 
  

  anti-nausea medications such as belladonna (Donnatal), dimenhydrinate (Dramamine), droperidol (Inapsine), methscopolamine (Pamine), or scopolamine (Transderm Scop);

  
  


• 
  

  bladder or urinary medications such as darifenacin (Enablex), flavoxate (Urispas), oxybutynin (Ditropan, Oxytrol), solifenacin (Vesicare), tolterodine (Detrol), or Urogesic Blue;

  
  


• 
  

  bronchodilators such as ipratropium (Atrovent) or tiotropium (Spiriva);

  
  


• 
  

  irritable bowel medications such as dicyclomine (Bentyl), hyoscyamine (Hyomax), or propantheline (Pro Banthine); or

  
  


• 
  

  ulcer medicine such as glycopyrrolate (Robinul) or mepenzolate (Cantil).

  
  

This list is not complete and other drugs may interact with dexbrompheniramine, dextromethorphan, and phenylephrine. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Dexall resources

• Dexall Use in Pregnancy & Breastfeeding
• Dexall Drug Interactions
• Dexall Support Group
• 0 Reviews for Dexall - Add your own review/rating

• Y-Cof DM Sustained-Release Tablets MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Dexall with other medications

• Cough and Nasal Congestion

Where can I get more information?

• Your pharmacist can provide more information about dexbrompheniramine, dextromethorphan, and phenylephrine.

Taltirelin

Scheme

Rec.INN

CAS registry number (Chemical Abstracts Service)

0103300-74-9

Chemical Formula

C17-H23-N7-O5

Molecular Weight

405

Therapeutic Category

Analogue of protirelin (thyrotropin releasing hormone, TRH)

Chemical Names

(S)-N-(1-methyl-4,5-dihydroorotyl)-L-histidyl-L-prolinamide

(-)-N-[[(S)-hexahydro-1-methyl-2,6-dioxo-4-pyrimidinyl]carbonyl]-L-histidyl-L-prolinamide (WHO)

N-{[(4S)-1-methyl-2,6-dioxohexahydropyrimidin-4-yl]carbonyl}-L-histidyl-L-prolinamide (IUPAC)

Foreign Names

• Taltirelinum (Latin)
• Taltirelin (German)
• Taltiréline (French)
• Taltirelina (Spanish)

Generic Names

• UNII-DOZ62MV6A5 (IS)
• Taltirelin Hydrate (OS: JAN)
• TA-0910 (IS)
• Taltirelin tetrahydrate (IS)

Brand Name

• Ceredist
  Tanabe Mitsubishi, Japan

International Drug Name Search

Glossary

IUPAC	International Union of Pure and Applied Chemistry
IS	Inofficial Synonym
JAN	Japanese Accepted Name
OS	Official Synonym
Rec.INN	Recommended International Nonproprietary Name (World Health Organization)
WHO	World Health Organization

Click for further information on drug naming conventions and International Nonproprietary Names.

Risperin

Risperin may be available in the countries listed below.

Ingredient matches for Risperin

Risperidone

Risperidone is reported as an ingredient of Risperin in the following countries:

• Argentina

International Drug Name Search

Amoxicillina Pliva

Amoxicillina Pliva may be available in the countries listed below.

Ingredient matches for Amoxicillina Pliva

Amoxicillin

Amoxicillin trihydrate (a derivative of Amoxicillin) is reported as an ingredient of Amoxicillina Pliva in the following countries:

• Italy

International Drug Name Search