Bilifalk

Bilifalk may be available in the countries listed below.

Ingredient matches for Bilifalk

Ursodeoxycholic Acid

Ursodeoxycholic Acid is reported as an ingredient of Bilifalk in the following countries:

• Spain

International Drug Name Search

Broncodual

Broncodual may be available in the countries listed below.

Ingredient matches for Broncodual

Clobutinol

Clobutinol is reported as an ingredient of Broncodual in the following countries:

• Chile

International Drug Name Search

Vitamin K1

In some countries, this medicine may only be approved for veterinary use.

In the US, Vitamin K1 (phytonadione systemic) is a member of the drug class vitamins and is used to treat Hypoprothrombinemia - Anticoagulant Induced, Hypoprothrombinemia - Not Associated with Anticoagulant Therapy, Hypoprothrombinemia - Prophylaxis and Vitamin K Deficiency.

US matches:

• Vitamin K1

Ingredient matches for Vitamin K1

Phytomenadione

Phytomenadione is reported as an ingredient of Vitamin K1 in the following countries:

• Australia


• Ireland


• Japan

International Drug Name Search

Celiprolol-CT

Celiprolol-CT may be available in the countries listed below.

Ingredient matches for Celiprolol-CT

Celiprolol

Celiprolol hydrochloride (a derivative of Celiprolol) is reported as an ingredient of Celiprolol-CT in the following countries:

• Germany

International Drug Name Search

Alendro-Q

Alendro-Q may be available in the countries listed below.

Ingredient matches for Alendro-Q

Alendronic Acid

Alendronic Acid sodium trihydrate (a derivative of Alendronic Acid) is reported as an ingredient of Alendro-Q in the following countries:

• Germany

International Drug Name Search

Sorbangil

Sorbangil may be available in the countries listed below.

Ingredient matches for Sorbangil

Isosorbide Dinitrate

Isosorbide Dinitrate is reported as an ingredient of Sorbangil in the following countries:

• Iceland


• Norway


• Sweden

International Drug Name Search

Artril

Artril may be available in the countries listed below.

Ingredient matches for Artril

Glucosamine

Glucosamine sulfate (a derivative of Glucosamine) is reported as an ingredient of Artril in the following countries:

• Singapore

Ibuprofen

Ibuprofen is reported as an ingredient of Artril in the following countries:

• Turkey

International Drug Name Search

Mycoril

Mycoril may be available in the countries listed below.

Ingredient matches for Mycoril

Clotrimazole

Clotrimazole is reported as an ingredient of Mycoril in the following countries:

• Cyprus


• Ethiopia


• Serbia


• Singapore


• Taiwan

International Drug Name Search

Cyclosporine Capsules

Cyclosporine Capsules USP (Modified)

WARNING

Only physicians experienced in management of systemic immunosuppressive therapy for the indicated disease should prescribe Cyclosporine Capsules USP (Modified). At doses used in solid organ transplantation, only physicians experienced in immunosuppressive therapy and management of organ transplant recipients should prescribe Cyclosporine Capsules USP (Modified). Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient.

Cyclosporine Capsules USP (Modified), a systemic immunosuppressant, may increase the susceptibility to infection and the development of neoplasia. In kidney, liver and heart transplant patients, Cyclosporine Capsules USP (Modified) may be administered with other immunosuppressive agents. Increased susceptibility to infection and the possible development of lymphoma and other neoplasms may result from the increase in the degree of immunosuppression in transplant patients.

Cyclosporine Capsules USP (Modified) have increased bioavailability in comparison to Sandimmune® Soft Gelatin Capsules (Cyclosporine Capsules, USP). Cyclosporine Capsules USP (Modified) and Sandimmune® are not bioequivalent and cannot be used interchangeably without physician supervision. For a given trough concentration, cyclosporine exposure will be greater with Cyclosporine Capsules USP (Modified) than with Sandimmune®. If a patient who is receiving exceptionally high doses of Sandimmune® is converted to Cyclosporine Capsules USP (Modified), particular caution should be exercised. Cyclosporine blood concentrations should be monitored in transplant and rheumatoid arthritis patients taking Cyclosporine Capsules USP (Modified) to avoid toxicity due to high concentrations. Dose adjustments should be made in transplant patients to minimize possible organ rejection due to low concentrations. Comparison of blood concentrations in the published literature with blood concentrations obtained using current assays must be done with detailed knowledge of the assay methods employed.

For Psoriasis Patients (See also boxed WARNINGS above)

Psoriasis patients previously treated with PUVA and to a lesser extent, methotrexate or other immunosuppressive agents, UVB, coal tar or radiation therapy, are at an increased risk of developing skin malignancies when taking Cyclosporine Capsules USP (Modified).

Cyclosporine, the active ingredient in Cyclosporine Capsules USP (Modified), in recommended dosages, can cause systemic hypertension and nephrotoxicity. The risk increases with increasing dose and duration of cyclosporine therapy. Renal dysfunction, including structural kidney damage, is a potential consequence of cyclosporine and therefore, renal function must be monitored during therapy.

Cyclosporine Capsules Description

Cyclosporine Capsules USP (Modified) is an oral formulation of cyclosporine that immediately forms a microemulsion in an aqueous environment.

Cyclosporine, the active principle in Cyclosporine Capsules USP (Modified), is a cyclic polypeptide immunosuppressant agent consisting of 11 amino acids. It is produced as a metabolite by the fungus species Beauveria nivea.

Chemically, cyclosporine is designated as [R - [R*,R* - (E)]] - cyclic - (L - alanyl - D - alanyl - N - methyl - L - leucyl - N - methyl - L - leucyl - N - methyl - L - valyl - 3 - hydroxy - N,4 - dimethyl - L - 2 - amino - 6 - octenoyl - L - α - amino - butyryl - N - methylglycyl - N - methyl - L - leucyl - L - valyl - N - methyl - L - leucyl).

Cyclosporine Capsules USP (Modified)

are available in 25 mg and 100 mg strengths.

Each 25 mg capsule contains:

Cyclosporine, USP………………………………………………………………...25 mg

Absolute alcohol…………….….................................................................15.8% v/v

Each 100 mg capsule contains:

Cyclosporine, USP……………………………………………………………...100 mg

Absolute alcohol…………….….................................................................18.1% v/v

Inactive Ingredients: d-α-tocopheryl polyethylene glycol 1000 succinate, gelatin, glycerin, polyoxyl 40 hydrogenated castor oil, polyethylene glycol 400, sorbitol.

The chemical structure of cyclosporine (also known as cyclosporin A) is:

Cyclosporine Capsules - Clinical Pharmacology

Cyclosporine is a potent immunosuppressive agent that in animals prolongs survival of allogeneic transplants involving skin, kidney, liver, heart, pancreas, bone marrow, small intestine and lung. Cyclosporine has been demonstrated to suppress some humoral immunity and to a greater extent, cell-mediated immune reactions such as allograft rejection, delayed hypersensitivity, experimental allergic encephalomyelitis, Freund’s adjuvant arthritis and graft vs. host disease in many animal species for a variety of organs.

The effectiveness of cyclosporine results from specific and reversible inhibition of immunocompetent lymphocytes in the G0- and G1-phase of the cell cycle. T-lymphocytes are preferentially inhibited. The T-helper cell is the main target, although the T-suppressor cell may also be suppressed. Cyclosporine also inhibits lymphokine production and release including interleukin-2.

No effects on phagocytic function (changes in enzyme secretions, chemotactic migration of granulocytes, macrophage migration, carbon clearance in vivo) have been detected in animals. Cyclosporine does not cause bone marrow suppression in animal models or man.

Pharmacokinetics

The immunosuppressive activity of cyclosporine is primarily due to parent drug. Following oral administration, absorption of cyclosporine is incomplete. The extent of absorption of cyclosporine is dependent on the individual patient, the patient population and the formulation. Elimination of cyclosporine is primarily biliary with only 6% of the dose (parent drug and metabolites) excreted in urine. The disposition of cyclosporine from blood is generally biphasic, with a terminal half-life of approximately 8.4 hours (range 5 to 18 hours). Following intravenous administration, the blood clearance of cyclosporine (assay: HPLC) is approximately 5 mL/min/kg to 7 mL/min/kg in adult recipients of renal or liver allografts. Blood cyclosporine clearance appears to be slightly slower in cardiac transplant patients.

The relationship between administered dose and exposure (area under the concentration versus time curve, AUC) is linear within the therapeutic dose range. The intersubject variability (total, %CV) of cyclosporine exposure (AUC) when cyclosporine (modified) or Sandimmune® is administered ranges from approximately 20% to 50% in renal transplant patients. This intersubject variability contributes to the need for individualization of the dosing regimen for optimal therapy (see DOSAGE AND ADMINISTRATION).  Intrasubject variability of AUC in renal transplant recipients (%CV) was 9% to 21% for cyclosporine (modified) and 19% to 26% for Sandimmune®. In the same studies, intrasubject variability of trough concentrations (%CV) was 17% to 30% for cyclosporine (modified) and 16% to 38% for Sandimmune®.

Absorption

  Cyclosporine (modified) has increased bioavailability compared to Sandimmune®. The absolute bioavailability of cyclosporine administered as Sandimmune® is dependent on the patient population, estimated to be less than 10% in liver transplant patients and as great as 89% in some renal transplant patients. The absolute bioavailability of cyclosporine administered as cyclosporine (modified) has not been determined in adults. In studies of renal transplant, rheumatoid arthritis and psoriasis patients, the mean cyclosporine AUC was approximately 20% to 50% greater and the peak blood cyclosporine concentration (Cmax) was approximately 40% to 106% greater following administration of cyclosporine (modified) compared to following administration of Sandimmune®. The dose normalized AUC in de novo liver transplant patients administered cyclosporine (modified) 28 days after transplantation was 50% greater and Cmax was 90% greater than in those patients administered Sandimmune®. AUC and Cmax are also increased (cyclosporine (modified) relative to Sandimmune®) in heart transplant patients, but data are very limited. Although the AUC and Cmax values are higher on cyclosporine (modified) relative to Sandimmune®, the pre-dose trough concentrations (dose-normalized) are similar for the two formulations.

Following oral administration of cyclosporine (modified), the time to peak blood cyclosporine concentrations (Tmax) ranged from 1.5 to 2.0 hours. The administration of food with cyclosporine (modified) decreases the cyclosporine AUC and Cmax. A high fat meal (669 kcal, 45 grams fat) consumed within one-half hour before cyclosporine (modified) administration decreased the AUC by 13% and Cmax by 33%. The effects of a low fat meal (667 kcal, 15 grams fat) were similar.

The effect of T-tube diversion of bile on the absorption of cyclosporine from cyclosporine (modified) was investigated in eleven de novo liver transplant patients. When the patients were administered cyclosporine (modified) with and without T-tube diversion of bile, very little difference in absorption was observed, as measured by the change in maximal cyclosporine blood concentrations from pre-dose values with the T-tube closed relative to when it was open: 6.9±41% (range -55% to 68%).

* Total daily dose was divided into two doses administered every 12 hours † AUC was measured over one dosing interval ‡ Trough concentration was measured just prior to the morning cyclosporine (modified) dose, approximately 12 hours after the previous dose § Assay: TDx specific monoclonal fluorescence polarization immunoassay ¶ Assay: Cyclo-trac specific monoclonal radioimmunoassay # Assay: INCSTAR specific monoclonal radioimmunoassay
Pharmacokinetic Parameters (mean±SD)
Patient population	Dose/day* (mg/d)	Dose/weight (mg/kg/d)	AUC† (ng·hr/mL)	Cmax (ng/mL)	Trough‡ (ng/mL)	CL/F (mL/min)	CL/F (mL/min/kg)
De novo renal transplant§ Week 4 (N=37)	597±174	7.95±2.81	8772±2089	1802±428	361±129	593±204	7.8±2.9
Stable renal transplant§ (N=55)	344±122	4.1±1.58	6035±2194	1333±469	251±116	492±140	5.9±2.1
De novo liver transplant¶ Week 4 (N=18)	458±190	6.89±3.68	7187±2816	1555±740	268±101	577±309	8.6±5.7
De novo rheumatoid arthritis# (N=23)	182±55.6	2.37±0.36	2641±877	728±263	96.4±37.7	613±196	8.3±2.8
De novo psoriasis# Week 4 (N=18)	189±69.8	2.48±0.65	2324±1048	655±186	74.9±46.7	723±186	10.2±3.9

Distribution

  Cyclosporine is distributed largely outside the blood volume. The steady state volume of distribution during intravenous dosing has been reported as 3 L/kg to 5 L/kg in solid organ transplant recipients. In blood, the distribution is concentration dependent. Approximately 33% to 47% is in plasma, 4% to 9% in lymphocytes, 5% to 12% in granulocytes and 41% to 58% in erythrocytes. At high concentrations, the binding capacity of leukocytes and erythrocytes becomes saturated. In plasma, approximately 90% is bound to proteins, primarily lipoproteins. Cyclosporine is excreted in human milk  (see PRECAUTIONS, Nursing Mothers ).

Metabolism

  Cyclosporine is extensively metabolized by the cytochrome P-450 3A enzyme system in the liver and to a lesser degree in the gastrointestinal tract and the kidney. The metabolism of cyclosporine can be altered by the co-administration of a variety of agents (see PRECAUTIONS, Drug Interactions). At least 25 metabolites have been identified from human bile, feces, blood and urine. The biological activity of the metabolites and their contributions to toxicity are considerably less than those of the parent compound. The major metabolites (M1, M9 and M4N) result from oxidation at the 1-beta, 9-gamma and 4-N-demethylated positions, respectively. At steady state following the oral administration of Sandimmune®, the mean AUCs for blood concentrations of M1, M9 and M4N are about 70%, 21% and 7.5% of the AUC for blood cyclosporine concentrations, respectively. Based on blood concentration data from stable renal transplant patients (13 patients administered cyclosporine (modified) and Sandimmune® in a crossover study) and bile concentration data from de novo liver transplant patients (4 administered cyclosporine (modified), 3 administered Sandimmune®), the percentage of dose present as M1, M9 and M4N metabolites is similar when either cyclosporine (modified) or Sandimmune® is administered.

Excretion

  Only 0.1% of a cyclosporine dose is excreted unchanged in the urine. Elimination is primarily biliary with only 6% of the dose (parent drug and metabolites) excreted in the urine. Neither dialysis nor renal failure alter cyclosporine clearance significantly.

Drug Interactions

  (see PRECAUTIONS, Drug Interactions). When diclofenac or methotrexate was co-administered with cyclosporine in rheumatoid arthritis patients, the AUC of diclofenac and methotrexate, each was significantly increased (see PRECAUTIONS, Drug Interactions). No clinically significant pharmacokinetic interactions occurred between cyclosporine and aspirin, ketoprofen, piroxicam or indomethacin.

Special Populations

  Pediatric Population

 Pharmacokinetic data from pediatric patients administered cyclosporine (modified) or Sandimmune® are very limited. In 15 renal transplant patients aged 3 to 16 years, cyclosporine whole blood clearance after IV administration of Sandimmune® was 10.6±3.7 mL/min/kg (assay: Cyclo-trac specific RIA). In a study of 7 renal transplant patients aged 2 to 16, the cyclosporine clearance ranged from 9.8 mL/min/kg to 15.5 mL/min/kg. In 9 liver transplant patients aged 0.6 to 5.6 years, clearance was 9.3±5.4 mL/min/kg (assay: HPLC).

In the pediatric population, cyclosporine (modified) also demonstrates an increased bioavailability as compared to Sandimmune®. In 7 liver de novo transplant patients aged 1.4 to 10 years, the absolute bioavailability of cyclosporine (modified) was 43% (range 30% to 68%) and for Sandimmune® in the same individuals absolute bioavailability was 28% (range 17% to 42%).

* AUC was measured over one dosing interval † Assay: Cyclo-trac specific monoclonal radioimmunoassay ‡ Assay: TDx specific monoclonal fluorescence polarization immunoassay
Pediatric Pharmacokinetic Parameters (mean±SD)
Patient Population	Dose/day (mg/d)	Dose/weight (mg/kg/d)	AUC* (ng·hr/mL)	Cmax (ng/mL)	CL/F (mL/min)	CL/F (mL/min/kg)
Stable liver transplant† Age 2 to 8, Dosed TID (N=9) Age 8 to 15, Dosed BID (N=8)	101±25 188±55	5.95±1.32 4.96±2.09	2163±801 4272±1462	629±219 975±281	285±94 378±80	16.6±4.3 10.2±4.0
Stable liver transplant‡ Age 3, Dosed BID (N=1) Age 8 to 15, Dosed BID (N=5)	120 158±55	8.33 5.51±1.91	5832 4452±2475	1050 1013±635	171 328±121	11.9 11.0±1.9
Stable renal transplant‡ Age 7 to 15, Dosed BID (N=5)	328±83	7.37±4.11	6922±1988	1827±487	418±143	8.7±2.9

Geriatric Population

 Comparison of single dose data from both normal elderly volunteers (N=18, mean age 69 years) and elderly rheumatoid arthritis patients (N=16, mean age 68 years) to single dose data in young adult volunteers (N=16, mean age 26 years) showed no significant difference in the pharmacokinetic parameters.

Clinical Trials

Rheumatoid Arthritis

The effectiveness of Sandimmune® and cyclosporine (modified) in the treatment of severe rheumatoid arthritis was evaluated in 5 clinical studies involving a total of 728 cyclosporine treated patients and 273 placebo treated patients.

A summary of the results is presented for the “responder” rates per treatment group, with a responder being defined as a patient having completed the trial with a 20% improvement in the tender and the swollen joint count and a 20% improvement in 2 of 4 of investigator global, patient global, disability and erythrocyte sedimentation rates (ESR) for the Studies 651 and 652 and 3 of 5 of investigator global, patient global, disability, visual analog pain and ESR for Studies 2008, 654 and 302.

Study 651 enrolled 264 patients with active rheumatoid arthritis with at least 20 involved joints, who had failed at least one major RA drug, using a 3:3:2 randomization to one of the following three groups: (1) cyclosporine dosed at 2.5 mg/kg/day to 5 mg/kg/day, (2) methotrexate at 7.5 mg/week to 15 mg/week or (3) placebo. Treatment duration was 24 weeks. The mean cyclosporine dose at the last visit was 3.1 mg/kg/day. See Graph below.

Study 652 enrolled 250 patients with active RA with >6 active painful or tender joints who had failed at least one major RA drug. Patients were randomized using a 3:3:2 randomization to 1 of 3 treatment arms: (1) 1.5 mg/kg/day to 5 mg/kg/day of cyclosporine, (2) 2.5 mg/kg/day to 5 mg/kg/day of cyclosporine and (3) placebo. Treatment duration was 16 weeks. The mean cyclosporine dose for group 2 at the last visit was 2.92 mg/kg/day. See Graph below.

Study 2008 enrolled 144 patients with active RA and >6 active joints who had unsuccessful treatment courses of aspirin and gold or Penicillamine. Patients were randomized to 1 of 2 treatment groups (1) cyclosporine 2.5 mg/kg/day to 5 mg/kg/day with adjustments after the first month to achieve a target trough level and (2) placebo. Treatment duration was 24 weeks. The mean cyclosporine dose at the last visit was 3.63 mg/kg/day. See Graph below.

Study 654 enrolled 148 patients who remained with active joint counts of 6 or more despite treatment with maximally tolerated methotrexate doses for at least three months. Patients continued to take their current dose of methotrexate and were randomized to receive, in addition, one of the following medications: (1) cyclosporine 2.5 mg/kg/day with dose increases of 0.5 mg/kg/day at weeks 2 and 4 if there was no evidence of toxicity and further increases of 0.5 mg/kg/day at weeks 8 and 16 if a <30% decrease in active joint count occurred without any significant toxicity; dose decreases could be made at any time for toxicity or (2) placebo. Treatment duration was 24 weeks. The mean cyclosporine dose at the last visit was 2.8 mg/kg/day (range: 1.3 to 4.1). See Graph below.

Study 302 enrolled 299 patients with severe active RA, 99% of whom were unresponsive or intolerant to at least one prior major RA drug. Patients were randomized to 1 of 2 treatment groups (1) cyclosporine (modified) and (2) cyclosporine, both of which were started at 2.5 mg/kg/day and increased after 4 weeks for inefficacy in increments of 0.5 mg/kg/day to a maximum of 5 mg/kg/day and decreased at any time for toxicity. Treatment duration was 24 weeks. The mean cyclosporine dose at the last visit was 2.91 mg/kg/day (range: 0.72 to 5.17) for cyclosporine (modified) and 3.27 mg/kg/day (range: 0.73 to 5.68) for cyclosporine. See Graph below.

Indications and Usage for Cyclosporine Capsules

Kidney, Liver, and Heart Transplantation

Cyclosporine Capsules USP (Modified) are indicated for the prophylaxis of organ rejection in kidney, liver and heart allogeneic transplants. Cyclosporine Capsules USP (Modified) have been used in combination with azathioprine and corticosteroids.

Rheumatoid Arthritis

Cyclosporine Capsules USP (Modified) are indicated for the treatment of patients with severe active, rheumatoid arthritis where the disease has not adequately responded to methotrexate. Cyclosporine Capsules USP (Modified) can be used in combination with methotrexate in rheumatoid arthritis patients who do not respond adequately to methotrexate alone.

Psoriasis

Cyclosporine Capsules USP (Modified) are indicated for the treatment of adult, nonimmunocompromised patients with severe (i.e., extensive and/or disabling), recalcitrant, plaque psoriasis who have failed to respond to at least one systemic therapy (eg., PUVA, retinoids or methotrexate) or in patients for whom other systemic therapies are contraindicated or cannot be tolerated.

While rebound rarely occurs, most patients will experience relapse with Cyclosporine Capsules USP (Modified) as with other therapies upon cessation of treatment.

Contraindications

General

Cyclosporine (modified) is contraindicated in patients with a hypersensitivity to cyclosporine or to any of the ingredients of the formulation.

Rheumatoid Arthritis

Rheumatoid arthritis patients with abnormal renal function, uncontrolled hypertension or malignancies should not receive cyclosporine (modified).

Psoriasis

Psoriasis patients who are treated with cyclosporine (modified) should not receive concomitant PUVA or UVB therapy, methotrexate or other immunosuppressive agents, coal tar or radiation therapy. Psoriasis patients with abnormal renal function, uncontrolled hypertension or malignancies should not receive cyclosporine (modified).

Warnings

(See also boxed WARNING)

All Patients

Cyclosporine, the active ingredient of cyclosporine (modified), can cause nephrotoxicity and hepatotoxicity. The risk increases with increasing doses of cyclosporine. Renal dysfunction including structural kidney damage is a potential consequence of cyclosporine (modified) and therefore renal function must be monitored during therapy. Care should be taken in using cyclosporine with nephrotoxic drugs (see PRECAUTIONS).

Patients receiving cyclosporine (modified) require frequent monitoring of serum creatinine (see Special Monitoring under DOSAGE AND ADMINISTRATION). Elderly patients should be monitored with particular care, since decreases in renal function also occur with age. If patients are not properly monitored and doses are not properly adjusted, cyclosporine therapy can be associated with the occurrence of structural kidney damage and persistent renal dysfunction.

An increase in serum creatinine and BUN may occur during cyclosporine (modified) therapy and reflect a reduction in the glomerular filtration rate. Impaired renal function at any time requires close monitoring and frequent dosage adjustment may be indicated. The frequency and severity of serum creatinine elevations increase with dose and duration of cyclosporine therapy. These elevations are likely to become more pronounced without dose reduction or discontinuation.

Because Cyclosporine Capsules (modified) are not bioequivalent to Sandimmune®, conversion from Cyclosporine Capsules (modified) to Sandimmune® using a 1:1 ratio (mg/kg/day) may result in lower cyclosporine blood concentrations. Conversion from Cyclosporine Capsules (modified) to Sandimmune® should be made with increased monitoring to avoid the potential of underdosing.

Kidney, Liver, and Heart Transplant

Cyclosporine, the active ingredient of cyclosporine (modified), can cause nephrotoxicity and hepatotoxicity when used in high doses. It is not unusual for serum creatinine and BUN levels to be elevated during cyclosporine therapy. These elevations in renal transplant patients do not necessarily indicate rejection and each patient must be fully evaluated before dosage adjustment is initiated.

Based on the historical Sandimmune® experience with oral solution, nephrotoxicity associated with cyclosporine had been noted in 25% of cases of renal transplantation, 38% of cases of cardiac transplantation and 37% of cases of liver transplantation. Mild nephrotoxicity was generally noted 2 to 3 months after renal transplant and consisted of an arrest in the fall of the pre-operative elevations of BUN and creatinine at a range of 35 mg/dL to 45 mg/dL and 2.0 mg/dL to 2.5 mg/dL respectively. These elevations were often responsive to cyclosporine dosage reduction.

More overt nephrotoxicity was seen early after transplantation and was characterized by a rapidly rising BUN and creatinine. Since these events are similar to renal rejection episodes, care must be taken to differentiate between them. This form of nephrotoxicity is usually responsive to cyclosporine dosage reduction.

Although specific diagnostic criteria which reliably differentiate renal graft rejection from drug toxicity have not been found, a number of parameters have been significantly associated with one or the other. It should be noted however, that up to 20% of patients may have simultaneous nephrotoxicity and rejection.

Nephrotoxicity vs. Rejection
Parameter	Nephrotoxicity	Rejection
History	Donor >50 years old or hypotensive Prolonged kidney preservation Prolonged anastomosis time Concomitant nephrotoxic drugs	Anti-donor immune response Retransplant patient
Clinical	Often >6 weeks postopb Prolonged initial nonfunction (acute tubular necrosis)	Often < 4 weeks postopb Fever > 37.5°C Weight gain > 0.5 kg Graft swelling and tenderness Decrease in daily urine volume > 500 mL (or 50%)
Laboratory	CyA serum trough level > 200 ng/mL Gradual rise in Cr (< 0.15 mg/dL/day)a Cr plateau < 25% above baseline BUN/Cr ≥ 20	CyA serum trough level < 150 ng/mL Rapid rise in Cr (> 0.3 mg/dL/day)a Cr > 25% above baseline BUN/Cr < 20
Biopsy	Arteriolopathy (medial hypertrophya, hyalinosis, nodular deposits, intimal thickening, endothelial vacuolization, progressive scarring) Tubular atrophy, isometric vacuolization, isolated calcifications Minimal edema Mild focal infiltratesc	Endovasculitisc (proliferationa, intimal arteritisb, necrosis, sclerosis) Tubulitis with RBCb and WBCb casts, some irregular vacuolization Interstitial edemac and hemorrhageb Diffuse moderate to severe mononuclear infiltratesd
Aspiration Cytology	Diffuse interstitial fibrosis, often striped form CyA deposits in tubular and endothelial cells Fine isometric vacuolization of tubular cells	Glomerulitis (mononuclear cells)c Inflammatory infiltrate with mononuclear phagocytes, macrophages, lymphoblastoid cells and activated T-cells These strongly express HLA-DR antigens
Urine Cytology	Tubular cells with vacuolization and granularization	Degenerative tubular cells, plasma cells, and lymphocyturia > 20% of sediment
Manometry Ultrasonography	Intracapsular pressure < 40 mm Hgb Unchanged graft cross sectional area	Intracapsular pressure > 40 mm Hgb Increase in graft cross sectional area AP diameter ≥ Transverse diameter
Magnetic Resonance Imagery	Normal appearance	Loss of distinct corticomedullary junction, swelling image intensity of parachyma approaching that of psoas, loss of hilar fat
Radionuclide Scan	Normal or generally decreased perfusion Decrease in tubular function (131 I-hippuran) > decrease in perfusion (99m Tc DTPA)	Patchy arterial flow Decrease in perfusion > decrease in tubular function Increased uptake of Indium 111 labeled platelets or Tc-99m in colloid
Therapy	Responds to decreased cyclosporine	Responds to increased steroids or antilymphocyte globulin

  ap < 0.05, bp < 0.01, cp < 0.001, dp < 0.0001

A form of a cyclosporine-associated nephropathy is characterized by serial deterioration in renal function and morphologic changes in the kidneys. From 5% to 15% of transplant recipients who have received cyclosporine will fail to show a reduction in rising serum creatinine despite a decrease or discontinuation of cyclosporine therapy. Renal biopsies from these patients will demonstrate one or several of the following alterations: tubular vacuolization, tubular microcalcifications, peritubular capillary congestion, arteriolopathy and a striped form of interstitial fibrosis with tubular atrophy. Though none of these morphologic changes are entirely specific, a diagnosis of cyclosporine-associated structural nephrotoxicity requires evidence of these findings.

When considering the development of cyclosporine-associated nephropathy, it is noteworthy that several authors have reported an association between the appearance of interstitial fibrosis and higher cumulative doses or persistently high circulating trough levels of cyclosporine. This is particularly true during the first 6 post-transplant months when the dosage tends to be highest and when, in kidney recipients, the organ appears to be most vulnerable to the toxic effects of cyclosporine. Among other contributing factors to the development of interstitial fibrosis in these patients are prolonged perfusion time, warm ischemia time, as well as episodes of acute toxicity and acute and chronic rejection. The reversibility of interstitial fibrosis and its correlation to renal function have not yet been determined. Reversibility of arteriolopathy has been reported after stopping cyclosporine or lowering the dosage.

Impaired renal function at any time requires close monitoring and frequent dosage adjustment may be indicated.

In the event of severe and unremitting rejection, when rescue therapy with pulse steroids and monoclonal antibodies fail to reverse the rejection episode, it may be preferable to switch to alternative immunosuppressive therapy rather than increase the cyclosporine (modified) dose to excessive levels.

Occasionally patients have developed a syndrome of thrombocytopenia and microangiopathic hemolytic anemia which may result in graft failure. The vasculopathy can occur in the absence of rejection and is accompanied by avid platelet consumption within the graft as demonstrated by Indium 111 labeled platelet studies. Neither the pathogenesis nor the management of this syndrome is clear. Though resolution has occurred after reduction or discontinuation of cyclosporine and 1) administration of streptokinase and heparin or 2) plasmapheresis, this appears to depend upon early detection with Indium 111 labeled platelet scans (see ADVERSE REACTIONS).

Significant hyperkalemia (sometimes associated with hyperchloremic metabolic acidosis) and hyperuricemia have been seen occasionally in individual patients.

Hepatotoxicity associated with cyclosporine use had been noted in 4% of cases of renal transplantation, 7% of cases of cardiac transplantation and 4% of cases of liver transplantation. This was usually noted during the first month of therapy when high doses of cyclosporine were used and consisted of elevations of hepatic enzymes and bilirubin. The chemistry elevations usually decreased with a reduction in dosage.

As in patients receiving other immunosuppressants, those patients receiving cyclosporine are at increased risk for development of lymphomas and other malignancies, particularly those of the skin. Patients taking cyclosporine should be warned to avoid excess ultraviolet light exposure. The increased risk appears related to the intensity and duration of immunosuppression rather than to the use of specific agents. Because of the danger of oversuppression of the immune system resulting in increased risk of infection or malignancy, a treatment regimen containing multiple immunosuppressants should be used with caution. Some malignancies may be fatal. Transplant patients receiving cyclosporine are at increased risk for serious infection with fatal outcome.

Latent Viral Infections

Immunosuppressed patients are at increased risk for opportunistic infections, including activation of latent viral infections. These include BK virus-associated nephropathy which has been observed in patients receiving immunosuppressants, including cyclosporine. This infection is associated with serious outcomes, including deteriorating renal function and renal graft loss. Patient monitoring may help detect patients at risk for BK virus-associated nephropathy. Reduction in immunosuppression should be considered for patients who develop evidence of BK virus-associated nephropathy.

There have been reports of convulsions in adult and pediatric patients receiving cyclosporine, particularly in combination with high dose methylprednisolone.

Encephalopathy has been described both in post-marketing reports and in the literature. Manifestations include impaired consciousness, convulsions, visual disturbances (including blindness), loss of motor function, movement disorders and psychiatric disturbances. In many cases, changes in the white matter have been detected using imaging techniques and pathologic specimens. Predisposing factors such as hypertension, hypomagnesemia, hypocholesterolemia, high-dose corticosteroids, high cyclosporine blood concentrations and graft-versus-host disease have been noted in many but not all of the reported cases. The changes in most cases have been reversible upon discontinuation of cyclosporine and in some cases improvement was noted after reduction of dose. It appears that patients receiving liver transplant are more susceptible to encephalopathy than those receiving kidney transplant. Another rare manifestation of cyclosporine-induced neurotoxicity, occurring in transplant patients more frequently than in other indications, is optic disc edema including papilloedema, with possible visual impairment, secondary to benign intracranial hypertension.

Care should be taken in using cyclosporine with nephrotoxic drugs (see PRECAUTIONS).

Rheumatoid Arthritis

Cyclosporine nephropathy was detected in renal biopsies of 6 out of 60 (10%) rheumatoid arthritis patients after the average treatment duration of 19 months. Only one patient, out of these 6 patients, was treated with a dose ≤4 mg/kg/day. Serum creatinine improved in all but one patient after discontinuation of cyclosporine. The “maximal creatinine increase” appears to be a factor in predicting cyclosporine nephropathy.

There is a potential, as with other immunosuppressive agents, for an increase in the occurrence of malignant lymphomas with cyclosporine. It is not clear whether the risk with cyclosporine is greater than that in rheumatoid arthritis patients or in rheumatoid arthritis patients on cytotoxic treatment for this indication. Five cases of lymphoma were detected: four in a survey of approximately 2,300 patients treated with cyclosporine for rheumatoid arthritis and another case of lymphoma was reported in a clinical trial. Although other tumors (12 skin cancers, 24 solid tumors of diverse types and 1 multiple myeloma) were also reported in this survey, epidemiologic analyses did not support a relationship to cyclosporine other than for malignant lymphomas.

Patients should be thoroughly evaluated before and during cyclosporine (modified) treatment for the development of malignancies. Moreover, use of cyclosporine (modified) therapy with other immunosuppressive agents may induce an excessive immunosuppression which is known to increase the risk of malignancy.

Psoriasis

(See also Boxed WARNINGS for Psoriasis)

Since cyclosporine is a potent immunosuppressive agent with a number of potentially serious side effects, the risks and benefits of using cyclosporine (modified) should be considered before treatment of patients with psoriasis. Cyclosporine, the active ingredient in cyclosporine (modified), can cause nephrotoxicity and hypertension (see PRECAUTIONS) and the risk increases with increasing dose and duration of therapy. Patients who may be at increased risk such as those with abnormal renal function, uncontrolled hypertension or malignancies, should not receive cyclosporine (modified).

Renal dysfunction is a potential consequence of cyclosporine (modified) therefore renal function must be monitored during therapy.

Patients receiving cyclosporine (modified) require frequent monitoring of serum creatinine (see Special Monitoring under DOSAGE AND ADMINISTRATION). Elderly patients should be monitored with particular care, since decreases in renal function also occur with age. If patients are not properly monitored and doses are not properly adjusted, cyclosporine therapy can cause structural kidney damage and persistent renal dysfunction.

An increase in serum creatinine and BUN may occur during cyclosporine (modified) therapy and reflects a reduction in the glomerular filtration rate.

Kidney biopsies from 86 psoriasis patients treated for a mean duration of 23 months with 1.2 mg/kg/day to 7.6 mg/kg/day of cyclosporine showed evidence of cyclosporine nephropathy in 18/86 (21%) of the patients. The pathology consisted of renal tubular atrophy and interstitial fibrosis. On repeat biopsy of 13 of these patients maintained on various dosages of cyclosporine for a mean of 2 additional years, the number with cyclosporine induced nephropathy rose to 26/86 (30%). The majority of patients (19/26) were on a dose of ≥5.0 mg/kg/day (the highest recommended dose is 4 mg/kg/day). The patients were also on cyclosporine for greater than 15 months (18/26) and/or had a clinically significant increase in serum creatinine for greater than 1 month (21/26). Creatinine levels returned to normal range in 7 of 11 patients in whom cyclosporine therapy was discontinued.

There is an increased risk for the development of skin and lymphoproliferative malignancies in cyclosporine-treated psoriasis patients. The relative risk of mal

Broomhexine Hydrochloride

Broomhexine Hydrochloride may be available in the countries listed below.

In some countries, this medicine may only be approved for veterinary use.

Ingredient matches for Broomhexine Hydrochloride

Bromhexine

Bromhexine hydrochloride (a derivative of Bromhexine) is reported as an ingredient of Broomhexine Hydrochloride in the following countries:

• Netherlands

International Drug Name Search

NAC-Hemofarm

NAC-Hemofarm may be available in the countries listed below.

Ingredient matches for NAC-Hemofarm

Acetylcysteine

Acetylcysteine is reported as an ingredient of NAC-Hemofarm in the following countries:

• Serbia

International Drug Name Search

Loperam

Loperam may be available in the countries listed below.

Ingredient matches for Loperam

Loperamide

Loperamide hydrochloride (a derivative of Loperamide) is reported as an ingredient of Loperam in the following countries:

• Venezuela

International Drug Name Search

dutasteride

doo-TAS-ter-ide

Commonly used brand name(s)

In the U.S.

• Avodart

Available Dosage Forms:

• Capsule, Liquid Filled

Therapeutic Class: Benign Prostatic Hypertrophy Agent

Pharmacologic Class: 5-Alpha Reductase Inhibitor

Uses For dutasteride

Note: Women of childbearing potential should not use or handle dutasteride capsules. Dutasteride can cause birth defects in male fetuses.

Dutasteride is used alone or in combination with tamsulosin (Flomax®) to treat men who have symptoms of an enlarged prostate gland, which is also known as benign prostatic hyperplasia (BPH). Benign enlargement of the prostate is a problem that can occur in men as they get older. The prostate gland is located below the bladder. As the prostate gland enlarges, certain muscles in the gland may become tight and get in the way of the tube that drains urine from the bladder. This can cause problems with urinating, such as a need to urinate often, a weak stream when urinating, or a feeling of not being able to empty the bladder completely.

Dutasteride blocks the action of an enzyme called 5-alpha-reductase. This enzyme changes testosterone to another hormone that causes the prostate to grow. As a result, the size of the prostate is decreased. The effect of dutasteride lasts only as long as the medicine is taken. If it is stopped, the prostate begins to grow again.

dutasteride is available only with your doctor's prescription.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in product labeling, dutasteride is used in certain patients with the following medical conditions:

• Male pattern alopecia.

Before Using dutasteride

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For dutasteride, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to dutasteride or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Dutasteride is not indicated for use in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of dutasteride in the elderly.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	X	Studies in animals or pregnant women have demonstrated positive evidence of fetal abnormalities. This drug should not be used in women who are or may become pregnant because the risk clearly outweighs any possible benefit.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking dutasteride, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using dutasteride with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Cimetidine


• Ciprofloxacin


• Diltiazem


• Ketoconazole


• Ritonavir


• Verapamil

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of dutasteride. Make sure you tell your doctor if you have any other medical problems, especially:

• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Proper Use of dutasteride

Take dutasteride exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

You may take dutasteride with or without food.

Swallow the capsule whole. Do not crush, chew, or open it. The contents of the capsule may irritate your lips, mouth, or throat.

dutasteride comes with a patient information leaflet. Read and follow these instructions carefully. Ask your doctor if you have any questions.

Dosing

The dose of dutasteride will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of dutasteride. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (capsules):
  
  • For benign prostatic hyperplasia:
    
    • Adults—0.5 milligram (mg) once a day.
    
    
    • Children—Use is not recommended.
    
    
  
  

Missed Dose

If you miss a dose of dutasteride, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using dutasteride

It is very important that your doctor check you at regular visits to make sure that dutasteride is working properly and to check for any unwanted effects that may be caused by dutasteride.

Women and children should not use dutasteride. Pregnant women or women who may become pregnant should not handle or touch the capsules. Dutasteride can be absorbed through the skin and can cause birth defects in male fetuses. If a pregnant woman does come in contact with dutasteride, the affected area should be washed right away with soap and water, especially if the capsule is broken.

Men who have taken dutasteride should not donate blood until 6 months have passed since the last dose. Dutasteride can remain in your blood for a long time and be passed on to a pregnant woman who receives a blood transfusion.

dutasteride may increase your risk of developing high-grade prostate cancer. Tell your doctor if you have concerns about this risk.

dutasteride may affect the results of the prostate specific antigen (PSA) test, which may be used to detect prostate cancer. Make sure you tell all of your doctors that you are using dutasteride.

dutasteride does not usually affect normal sexual abilities for most men. You may notice that you ejaculate less fluid when you have sex.

dutasteride Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

Rare

• Chest pain or discomfort


• dilated neck veins


• extreme fatigue


• irregular breathing


• irregular heartbeat


• shortness of breath


• swelling of the face, fingers, feet, or lower legs


• weight gain


• wheezing

Incidence not known

• Blistering, flaking, or peeling of the skin


• cough


• difficulty with swallowing


• dizziness


• fast heartbeat


• hives or welts


• itching skin


• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs


• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue


• redness of the skin


• skin rash


• tightness in the chest


• unusual tiredness or weakness


• wheezing

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common

• Abnormal ejaculation


• decreased interest in sexual intercourse


• decreased sexual performance or desire


• impotence


• inability to have or keep an erection


• loss in sexual ability, desire, drive, or performance


• pain, soreness, swelling, or discharge from the breast or breasts

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

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

See also: dutasteride side effects (in more detail)

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More dutasteride resources

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

• Dutasteride Professional Patient Advice (Wolters Kluwer)


• Dutasteride Monograph (AHFS DI)


• Dutasteride MedFacts Consumer Leaflet (Wolters Kluwer)


• Avodart Prescribing Information (FDA)


• Avodart Consumer Overview

Compare dutasteride with other medications

• Benign Prostatic Hyperplasia

Bonal

Bonal may be available in the countries listed below.

Ingredient matches for Bonal

Hyaluronic Acid

Hyaluronic Acid is reported as an ingredient of Bonal in the following countries:

• Turkey

International Drug Name Search

Betamed

In the US, Betamed is a member of the drug class vitamin and mineral combinations and is used to treat Vitamin/Mineral Supplementation and Deficiency.

Ingredient matches for Betamed

Betamethasone

Betamethasone 17α-valerate (a derivative of Betamethasone) is reported as an ingredient of Betamed in the following countries:

• Bahrain


• Oman

International Drug Name Search

Citalopram Arrow

Citalopram Arrow may be available in the countries listed below.

Ingredient matches for Citalopram Arrow

Citalopram

Citalopram hydrobromide (a derivative of Citalopram) is reported as an ingredient of Citalopram Arrow in the following countries:

• Denmark


• France


• Netherlands


• New Zealand


• Sweden

International Drug Name Search

Bovimec

Bovimec may be available in the countries listed below.

In some countries, this medicine may only be approved for veterinary use.

Ingredient matches for Bovimec

Ivermectin

Ivermectin is reported as an ingredient of Bovimec in the following countries:

• Belgium

International Drug Name Search

Venlafaxina Bexal

Venlafaxina Bexal may be available in the countries listed below.

Ingredient matches for Venlafaxina Bexal

Venlafaxine

Venlafaxine hydrochloride (a derivative of Venlafaxine) is reported as an ingredient of Venlafaxina Bexal in the following countries:

• Spain

International Drug Name Search

Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid

Pronunciation: klor-fen-IHR-ah-meen/fen-ill-EF-rin /fen-ill-tole-OX-a-meen
Generic Name: Chlorpheniramine/Phenylephrine/Phenyltoloxamine
Brand Name: Examples include Nalex-A and Rhinacon A

Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid is used for:

Relieving symptoms of sinus congestion, pressure, runny nose, and sneezing due to colds, upper respiratory infections, and allergies. It may also be used for other conditions as determined by your doctor.

Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid is an antihistamine and decongestant combination. The antihistamine works by blocking the action of histamine, which helps reduce symptoms such as watery eyes and sneezing. The decongestant promotes sinus and nasal drainage, which relieves congestion and pressure.

Do NOT use Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid if:

• you are allergic to any ingredient in Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid


• you have severe high blood pressure, severe heart blood vessel disease, rapid heartbeat, or severe heart problems


• you take sodium oxybate (GHB) or if you have taken furazolidone or a monoamine oxidase (MAO) inhibitor (eg, phenelzine) within the last 14 days

Contact your doctor or health care provider right away if any of these apply to you.

Before using Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid:

Some medical conditions may interact with Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, plan to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have a fast, slow, or irregular heartbeat


• if you have a history of asthma; lung problems (eg, emphysema); adrenal gland problems (eg, adrenal gland tumor); heart problems; high blood pressure; diabetes; heart blood vessel problems; stroke; glaucoma; a blockage of your bladder, stomach, or intestines; ulcers; trouble urinating; an enlarged prostate; seizures; or an overactive thyroid

Some MEDICINES MAY INTERACT with Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Beta-blockers (eg, propranolol), COMT inhibitors (eg, tolcapone), furazolidone, indomethacin, MAO inhibitors (eg, phenelzine), sodium oxybate (GHB), or tricyclic antidepressants (eg, amitriptyline) because side effects of Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid may be increased


• Digoxin or droxidopa because risk of irregular heartbeat or heart attack may be increased


• Bromocriptine or hydantoins (eg, phenytoin) because side effects may be increased by Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid


• Guanadrel, guanethidine, mecamylamine, methyldopa, or reserpine because effectiveness may be decreased by Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid

This may not be a complete list of all interactions that may occur. Ask your health care provider if Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid:

Use Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid may be taken with or without food.


• Use a measuring device marked for medicine dosing. Ask your pharmacist for help if you are unsure of how to measure your dose.


• If you miss a dose of Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid.

Important safety information:

• Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid may cause dizziness, drowsiness, or blurred vision. Do not drive, operate machinery, or do anything else that could be dangerous until you know how you react to Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid. Using Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid alone, with certain other medicines, or with alcohol may lessen your ability to drive or perform other potentially dangerous tasks.


• Do not take diet or appetite control medicines while you are taking Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid without checking with your doctor.


• Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid contains phenylephrine. Before you begin taking any new prescription or nonprescription medicine, read the ingredients to see if it also contains phenylephrine. If it does or if you are uncertain, contact your doctor or pharmacist.


• Do NOT exceed the recommended dose or take Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid for longer than prescribed without checking with your doctor.


• If your symptoms do not improve within 5 to 7 days or if they become worse, check with your doctor.


• Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid may cause increased sensitivity to the sun. Avoid exposure to the sun, sunlamps, or tanning booths until you know how you react to Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid. Use a sunscreen or protective clothing if you must be outside for a prolonged period.


• If you are scheduled for allergy skin testing, do not take Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid for several days before the test because it may decrease your response to the skin tests.


• Before you have any medical or dental treatments, emergency care, or surgery, tell the doctor or dentist that you are using Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid.


• Use Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid with caution in the ELDERLY because they may be more sensitive to its effects.


• Caution is advised when using Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid in CHILDREN because they may be more sensitive to its effects.


• PREGNANCY and BREAST-FEEDING: If you become pregnant while taking Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid, discuss with your doctor the benefits and risks of using Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid during pregnancy. It is unknown if Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid is excreted in breast milk. Do not breast-feed while taking Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid.

Possible side effects of Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Constipation; diarrhea; dizziness; drowsiness; excitability; headache; loss of appetite; nausea; nervousness or anxiety; trouble sleeping; upset stomach; vomiting; weakness.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); difficulty urinating or inability to urinate; fast or irregular heartbeat; hallucinations; seizures; severe dizziness, lightheadedness, or headache; tremor; trouble sleeping; vision changes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Chlorpheniramine/Phenylephrine/Phenyltoloxamine side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include blurred vision; confusion; hallucinations; seizures; severe dizziness, lightheadedness, or headache; severe drowsiness; unusually fast, slow, or irregular heartbeat; vomiting.

Proper storage of Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid:

Store Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid out of the reach of children and away from pets.

General information:

• If you have any questions about Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid, please talk with your doctor, pharmacist, or other health care provider.


• Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Chlorpheniramine/Phenylephrine/Phenyltoloxamine Liquid. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Chlorpheniramine/Phenylephrine/Phenyltoloxamine resources

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

Compare Chlorpheniramine/Phenylephrine/Phenyltoloxamine with other medications

• Cold Symptoms
• Nasal Congestion
• Sinus Symptoms

Brionot

Brionot may be available in the countries listed below.

Ingredient matches for Brionot

Piroxicam

Piroxicam is reported as an ingredient of Brionot in the following countries:

• Argentina

International Drug Name Search

Dexametason

Dexametason may be available in the countries listed below.

Ingredient matches for Dexametason

Dexamethasone

Dexamethasone is reported as an ingredient of Dexametason in the following countries:

• Finland


• Russian Federation

International Drug Name Search

Bronco Medical

Bronco Medical may be available in the countries listed below.

Ingredient matches for Bronco Medical

Dextromethorphan

Dextromethorphan hydrobromide (a derivative of Dextromethorphan) is reported as an ingredient of Bronco Medical in the following countries:

• Spain

Sulfogaiacol

Sulfogaiacol is reported as an ingredient of Bronco Medical in the following countries:

• Spain

International Drug Name Search

Bifrizide

Bifrizide may be available in the countries listed below.

Ingredient matches for Bifrizide

Hydrochlorothiazide

Hydrochlorothiazide is reported as an ingredient of Bifrizide in the following countries:

• Italy

Zofenopril

Zofenopril calcium salt (a derivative of Zofenopril) is reported as an ingredient of Bifrizide in the following countries:

• Italy

International Drug Name Search

Alvastin

Alvastin may be available in the countries listed below.

Ingredient matches for Alvastin

Atorvastatin

Atorvastatin calcium (a derivative of Atorvastatin) is reported as an ingredient of Alvastin in the following countries:

• Turkey

International Drug Name Search

Ritosin

Ritosin may be available in the countries listed below.

Ingredient matches for Ritosin

Roxithromycin

Roxithromycin is reported as an ingredient of Ritosin in the following countries:

• Turkey

International Drug Name Search

Bimadine

Bimadine may be available in the countries listed below.

In some countries, this medicine may only be approved for veterinary use.

Ingredient matches for Bimadine

Sulfadimidine

Sulfadimidine is reported as an ingredient of Bimadine in the following countries:

• United Kingdom

Sulfadimidine sodium salt (a derivative of Sulfadimidine) is reported as an ingredient of Bimadine in the following countries:

• United Kingdom

International Drug Name Search

Benestermycin

Benestermycin may be available in the countries listed below.

In some countries, this medicine may only be approved for veterinary use.

Ingredient matches for Benestermycin

Benzylpenicillin

Benzylpenicillin is reported as an ingredient of Benestermycin in the following countries:

• Austria

Benzylpenicillin benethamin (a derivative of Benzylpenicillin) is reported as an ingredient of Benestermycin in the following countries:

• Austria


• Germany


• Sweden

Framycetin

Framycetin sulfate (a derivative of Framycetin) is reported as an ingredient of Benestermycin in the following countries:

• Austria

Penethamate Hydriodide

Penethamate Hydriodide is reported as an ingredient of Benestermycin in the following countries:

• Germany


• Sweden

International Drug Name Search

GenRX Cefaclor

GenRX Cefaclor may be available in the countries listed below.

Ingredient matches for GenRX Cefaclor

Cefaclor

Cefaclor monohydrate (a derivative of Cefaclor) is reported as an ingredient of GenRX Cefaclor in the following countries:

• Australia

International Drug Name Search

Bamethan

Scheme

Rec.INN

ATC (Anatomical Therapeutic Chemical Classification)

C04AA31

CAS registry number (Chemical Abstracts Service)

0003703-79-5

Chemical Formula

C12-H19-N-O2

Molecular Weight

209

Therapeutic Category

Vasodilator, peripheric

Chemical Name

Benzenemethanol, α-[(butylamino)methyl]-4-hydroxy-

Foreign Names

• Bamethanum (Latin)
• Bamethan (German)
• Baméthan (French)
• Bametan (Spanish)

Generic Names

• Bametano (OS: DCIT)
• Bamethan (OS: BAN)
• Baméthan (OS: DCF)
• Butyl-Nor-Sympatol (IS)
• Butyl-nor-synephrin (IS)
• P 138 (IS)
• Bamethan Sulfate (OS: USAN)
• Bamethan Sulphate (OS: BANM)
• Bamethanum sulfuricum (IS)
• BOL (IS)
• Bamethan Sulfate (PH: JP XV)

Brand Names

• Dilartan
  Duncan, Argentina



• Vasculat
  Boehringer Ingelheim, Brazil

International Drug Name Search

Glossary

BAN	British Approved Name
BANM	British Approved Name (Modified)
DCF	Dénomination Commune Française
DCIT	Denominazione Comune Italiana
IS	Inofficial Synonym
OS	Official Synonym
PH	Pharmacopoeia Name
Rec.INN	Recommended International Nonproprietary Name (World Health Organization)
USAN	United States Adopted Name

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

Buflo-POS

Buflo-POS may be available in the countries listed below.

Ingredient matches for Buflo-POS

Buflomedil

Buflomedil hydrochloride (a derivative of Buflomedil) is reported as an ingredient of Buflo-POS in the following countries:

• Germany

International Drug Name Search