Tetralysal 300

1. Name Of The Medicinal Product

Tetralysal 300mg Hard Capsules

2. Qualitative And Quantitative Composition

Each capsule contains 408mg of Lymecycline equivalent to 300mg tetracycline base

For a full list of excipients, see section 6.1

3. Pharmaceutical Form

Hard capsule

Hard gelatin capsule, red cap and yellow body

4. Clinical Particulars

4.1 Therapeutic Indications

Tetralysal is indicated for the treatment of infections caused by tetracycline sensitive organisms (please see section 4.4 and 5.1) including the following:

• Acne

• Ear, nose and throat infections

• Acute exacerbation of chronic bronchitis

• Gastro-intestinal infection

• Urinary tract infection

• Non-gonococcal urethritis

• Trachoma

• Rickettsial fever

• Soft tissue infection

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

4.2 Posology And Method Of Administration

Adults:

The usual dosage for the chronic treatment of acne is 1 capsule daily: treatment should be continued for at least 8 weeks.

For other infections, the usual dosage is 1 capsule b.d. If higher doses are required, 3-4 capsules may be given over 24 hours. Lower doses may be given for prophylaxis.

In the management of sexually transmitted disease both partners should be treated.

Elderly:

As for other tetracyclines, no specific dose adjustment is required.

Children:

Not recommended for children under the age of 12 years. For children over the age of 12 years the adult dosage may be given.

4.3 Contraindications

Hypersensitivity to lymecycline or any other tetracycline or to any of the excipients.

Its use is contraindicated in patients with overt renal insufficiency and in children less than 12 years.

4.4 Special Warnings And Precautions For Use

Prolonged use of broad spectrum antibiotics may result in the appearance of resistant organisms and superinfection.

Care should be exercised in administering tetracyclines to patients with hepatic impairment. Tetracyclines may cause photosensitivity reactions; however, very rare cases have been reported with lymecycline.

May cause exacerbation of systemic lupus erythematosus. Can cause weak neuromuscular blockade so should be used with caution in Myasthenia Gravis.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

The absorption of tetracyclines may be affected by the simultaneous administration of calcium, aluminium, magnesium, bismuth and zinc salts, antacids, Bismuth containing ulcer-healing drugs, iron preparations and quinapril. These products should not be taken within two hours before or after taking Tetralysal 300.

Unlike earlier tetracyclines, absorption of Tetralysal 300 is not significantly impaired by moderate amounts of milk.

Concomitant use of oral retinoids should be avoided as this may increase the risk of benign intracranial hypertension. An increase in the effects of anticoagulants may occur with tetracyclines. Concomitant use of diuretics should be avoided.

Although not reported for Tetralysal 300, a few cases of pregnancy or breakthrough bleeding have been attributed to the concurrent use of tetracycline or oxytetracycline with oral contraceptives.

4.6 Pregnancy And Lactation

Tetracyclines are selectively absorbed by developing bones and teeth and may cause dental staining and enamel hypoplasia. In addition these compounds readily cross the placental barrier and therefore Tetralysal 300 should not be given to pregnant or lactating women.

4.7 Effects On Ability To Drive And Use Machines

No studies on the effects on the ability to drive and use machines have been performed

4.8 Undesirable Effects

The most frequently reported adverse events with Tetralysal are gastrointestinal disorders of nausea, abdominal pain, diarrhoea and nervous system disorder of headache. The most serious adverse events reported with Tetralysal are Stevens Johnson syndrome, anaphylactic reaction, angioneurotic oedema and intracranial hypertension.

System Organ Class	Frequency	Adverse Reaction
Blood and lymphatic system disorders	Unknown	Neutropenia Thrombocytopenia
Eye disorders	Unknown	Visual disturbance
Gastrointestinal disorders	Common (	Nausea Abdominal pain Diarrhoea
	Unknown	Epigastralgia Glossitis Vomiting Enterocolitis
General disorders and administration site conditions	Unknown	Pyrexia
Hepatobiliary disorders	Unknown	Jaundice
Immune system disorder	Unknown	Anaphylactic reaction Hypersensitivity Urticaria Angioneurotic oedema
Investigations	Unknown	Transaminases increased Blood alkaline phosphatase increased Blood bilirubin increased
Nervous system disorders	Common (	Headache
	Unknown	Dizziness Intracranial hypertension
Skin and subcutaneus tissues disorders	Unknown	Erythematous rash Photosensitivity Pruritus Stevens Johnson syndrome

General tetracyclines adverse events:

Benign intracranial hypertension and bulging fontanelles in infants were reported with tetracyclines with possible symptoms of headaches, visual disturbances including blurring of vision, scotomata, diplopia or permanent visual loss.

The following adverse effects were reported with tetracyclines in general and may occur with Tetralysal: dysphagia, oesophagitis, oesophageal ulceration, pancreatitis, teeth discolouration, hepatitis, hepatic failure. Dental dyschromia and/or enamel hypoplasia may occur if the product is administered in children younger than 8 years of age

As with all antibiotics overgrowth of non susceptible organisms may cause candidiasis, pseudomembranous colitis (Clostridium Difficile overgrowth), glossitis, stomatitis, vaginitis or staphyloccocal enterocolitis.

4.9 Overdose

There is no specific treatment, but gastric lavage should be performed as soon as possible. Supportive measure should be instituted as required and a high fluid intake maintained.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Tetracyclines

ATC code: J01AA04

Mode of action

Tetracyclines provide bacteriostatic action at the available plasma and tissue concentrations and are effective against intracellular and extracellular organisms. Their mechanism of action is based on an inhibition of ribosomal protein synthesis. Tetracyclines block the access of the bacterial aminoacyl-tRNA to the mRNA-ribosome complex by binding to the 30S subunit of the ribosome, thus preventing the addition of amino acids to the growing peptide chain in protein synthesis. When given at therapeutically attainable concentrations their toxic effect is limited to the bacterial cells.

The exact mechanisms by which tetracyclines reduce lesions of acne vulgaris have not been fully elucidated; however, the effect appears to result in part from the antibacterial activity of the drugs. Following oral administration, the drugs inhibit the growth of susceptible organisms (mainly Propionibacterium acnes) on the surface of the skin and reduce the concentration of free fatty acids in sebum. The reduction in free fatty acids in sebum may be an indirect result of the inhibition of lipase-producing organisms which convert triglycerides into free fatty acids or may be a direct result of interference with lipase production in these organisms. Free fatty acids are comedogenic and are believed to be a possible cause of the inflammatory lesions, e.g. papules, pustules, nodules, cysts, of acne. However, other mechanisms also appear to be involved because clinical improvement of acne vulgaris with oral tetracycline therapy does not necessarily correspond with a reduction in the bacterial flora of the skin or a decrease in the free fatty acid content of sebum.

Mechanism of resistance

Tetracycline resistance in propionibacteria is usually associated with a single point mutation within the gene encoding 16S rRNA. Clinical isolates resistant to tetracycline were found to have cytosine instead of guanine at a position cognate with Escherichia coli base 1058. There is no evidence that ribosome mutations can be transferred between different strains or species of propionibacteria, or between propionibacteria and other skin commensals.

Resistance to the tetracyclines is associated with mobile resistance determinants in both staphylococci and coryneform bacteria. These determinants are potentially transmissible between different species and even different genera of bacteria.

In all three genera, cross-resistance with the macrolide-lincosamide-streptogramin group of antibiotics cannot be ruled out.

Strains of propionibacteria resistant to the hydrophilic tetracyclines are cross-resistant to doxycycline and may or may not show reduced susceptibility to minocycline.

Breakpoints

For tetracycline resistance in anaerobic and most aerobic bacteria, the breakpoints as set by the NCCLS are:

Susceptible MIC < 4 mg/L

Intermediate MIC 8 mg/L

Resistant MIC > 16 mg/L

In cutaneous propionibacteria, mutational resistance is associated with MICs of tetracycline > 2mg/L.

Susceptibility table

The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.

Susceptibility to tetracyclines of species relevant to the approved indication

Commonly susceptible species

Gram-positive aerobes

None of relevance

Gram-negative aerobes

None of relevance

Anaerobes

Propionbacterium acnes (clinical isolates)*

Other

None of relevance

Species for which acquired resistance may be a problem (defined as >10% resistant within any European country)

Gram-positive aerobes

S. aureus (methicillin susceptible)

S. aureus (methicillin resistant) +

Coagulase-negative staphylococci (methicillin susceptible)

Coagulase-negative staphylococci (methicillin resistant) +

Corynebacterium spp

Species for which acquired resistance may be a problem (defined as >10% resistant within any European country)

Gram-negative aerobes

None of relevance

Anaerobes

Propionibacterium acnes (isolates from acne)* +

Other (microaerophile)

None of relevance

Inherently resistant species

None of relevance

However, even if resistance to cutaneous propionibacteria is detected, this does not automatically translate into therapeutic failure, since the antiinflammatory activity of the tetracyclines is not compromised by resistance in the target bacteria.

5.2 Pharmacokinetic Properties

Lymecycline is more readily absorbed from the gastro-intestinal tract than tetracycline, with a peak serum concentration of approximately 2mg/L after 3 hours following a 300 mg dose. In addition, similar blood concentrations are achieved with small doses. When the dose is doubled an almost correspondingly higher blood concentration has been reported to occur.

The serum half-life of lymecycline is approximately 10 hours.

5.3 Preclinical Safety Data

No specific information is presented given the vast experience gained with the use of tetracyclines in humans over the last forty years.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Magnesium stearate

Colloidal hydrated silica

The capsule shells contain

gelatin

titanium dioxide (E171)

erythrosine (E127)

quinoline yellow (E104)

indigotine (E132)

6.2 Incompatibilities

Not applicable

6.3 Shelf Life

3 years (unopened)

6.4 Special Precautions For Storage

Aluminium and polyethylene strips: Do not store above 25ºC.

Store in the original container.

Aluminium-PVC/PVDC calendar blister strips: Do not store above 25ºC.

Keep container in the outer carton.

As with all medicines, Tetralysal 300 should be kept out of the sight and reach of children.

6.5 Nature And Contents Of Container

Aluminium-PVC/PVDC calendar blister strips of 14 capsules; two strips per carton, pack size = 28 capsules or Aluminium and polyethylene strips 28 or 56 capsule pack size.

Not all pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

No special requirements

7. Marketing Authorisation Holder

Galderma (UK) Limited

Meridien House

69-71 Clarendon Road

Watford

Herts.

WD17 1DS

UK

8. Marketing Authorisation Number(S)

PL 10590/0019

9. Date Of First Authorisation/Renewal Of The Authorisation

29^th September 1995

10. Date Of Revision Of The Text

June 2009

Hydrochlorothiazide Capsules

Hydrochlorothiazide Capsules, 12.5 mg

Rx Only

Hydrochlorothiazide Capsules Description

Hydrochlorothiazide is the 3,4-dihydro derivative of chlorothiazide. Its chemical name is 6-Chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its empirical formula is C7H8ClN3O4S2; its molecular weight is 297.74; and its structural formula is:

It is a white, or practically white, crystalline powder which is slightly soluble in water, but freely soluble in sodium hydroxide solution.

Hydrochlorothiazide is supplied as 12.5 mg capsules for oral use. Inactive ingredients: lactose monohydrate, pregelatinized corn starch, sodium starch glycolate, magnesium stearate and colloidal silicon dioxide. Gelatin capsules contain D&C Red #28, D&C Yellow #10, FD&C Blue #1, gelatin and titanium dioxide. The capsule imprinting ink contains shellac glaze in ethanol, black iron oxide, n-butyl alcohol, propylene glycol, methanol, ethanol, FD&C Blue #2 Aluminum Lake, FD&C Red #40 Aluminum Lake, FD&C Blue #1 Aluminum Lake and D&C Yellow #10 Aluminum Lake.

Hydrochlorothiazide Capsules - Clinical Pharmacology

Hydrochlorothiazide blocks the reabsorption of sodium and chloride ions, and it thereby increases the quantity of sodium traversing the distal tubule and the volume of water excreted. A portion of the additional sodium presented to the distal tubule is exchanged there for potassium and hydrogen ions. With continued use of hydrochlorothiazide and depletion of sodium, compensatory mechanisms tend to increase this exchange and may produce excessive loss of potassium, hydrogen and chloride ions. Hydrochlorothiazide also decreases the excretion of calcium and uric acid, may increase the excretion of iodide and may reduce glomerular filtration rate. Metabolic toxicities associated with excessive electrolyte changes caused by hydrochlorothiazide have been shown to be dose-related.

Pharmacokinetics and Metabolism

Hydrochlorothiazide is well absorbed (65% to 75%) following oral administration. Absorption of hydrochlorothiazide is reduced in patients with congestive heart failure.

Peak plasma concentrations are observed within 1 to 5 hours of dosing, and range from 70 to 490 ng/mL following oral doses of 12.5 to 100 mg. Plasma concentrations are linearly related to the administered dose. Concentrations of hydrochlorothiazide are 1.6 to 1.8 times higher in whole blood than in plasma. Binding to serum proteins has been reported to be approximately 40% to 68%. The plasma elimination half-life has been reported to be 6 to 15 hours. Hydrochlorothiazide is eliminated primarily by renal pathways. Following oral doses of 12.5 to 100 mg, 55% to 77% of the administered dose appears in urine and greater than 95% of the absorbed dose is excreted in urine as unchanged drug. In patients with renal disease, plasma concentrations of hydrochlorothiazide are increased and the elimination half-life is prolonged.

When hydrochlorothiazide is administered with food, its bioavailability is reduced by 10%, the maximum plasma concentration is reduced by 20%, and the time to maximum concentration increases from 1.6 to 2.9 hours.

Pharmacodynamics

Acute antihypertensive effects of thiazides are thought to result from a reduction in blood volume and cardiac output, secondary to a natriuretic effect, although a direct vasodilatory mechanism has also been proposed. With chronic administration, plasma volume returns toward normal, but peripheral vascular resistance is decreased. The exact mechanism of the antihypertensive effect of hydrochlorothiazide is not known.

Thiazides do not affect normal blood pressure. Onset of action occurs within 2 hours of dosing, peak effect is observed at about 4 hours, and activity persists for up to 24 hours.

Clinical Studies

In an 87 patient 4-week double-blind, placebo controlled, parallel group trial, patients who received hydrochlorothiazide had reductions in seated systolic and diastolic blood pressure that were significantly greater than those seen in patients who received placebo. In published placebo-controlled trials comparing 12.5 mg of hydrochlorothiazide to 25 mg, the 12.5 mg dose preserved most of the placebo-corrected blood pressure reduction seen with 25 mg.

Indications and Usage for Hydrochlorothiazide Capsules

Hydrochlorothiazide Capsules are indicated in the management of hypertension either as the sole therapeutic agent, or in combination with other antihypertensives. Unlike potassium sparing combination diuretic products, hydrochlorothiazide may be used in those patients in whom the development of hyperkalemia cannot be risked, including patients taking ACE inhibitors.

Usage in Pregnancy: The routine use of diuretics in an otherwise healthy woman is inappropriate and exposes mother and fetus to unnecessary hazard. Diuretics do not prevent development of toxemia of pregnancy, and there is no satisfactory evidence that they are useful in the treatment of developed toxemia.

Edema during pregnancy may arise from pathological causes or from the physiologic and mechanical consequences of pregnancy. Diuretics are indicated in pregnancy when edema is due to pathologic causes, just as they are in the absence of pregnancy. Dependent edema in pregnancy resulting from restriction of venous return by the expanded uterus is properly treated through elevation of the lower extremities and use of support hose; use of diuretics to lower intravascular volume in this case is illogical and unnecessary. There is hypervolemia during normal pregnancy which is harmful to neither the fetus nor the mother (in the absence of cardiovascular disease), but which is associated with edema, including generalized edema in the majority of pregnant women. If this edema produces discomfort, increased recumbency will often provide relief. In rare instances this edema may cause extreme discomfort which is not relieved by rest. In these cases a short course of diuretics may provide relief and may be appropriate.

Contraindications

Hydrochlorothiazide Capsules are contraindicated in patients with anuria. Hypersensitivity to this product or other sulfonamide derived drugs is also contraindicated.

Warnings

Acute Myopia and Secondary Angle-Closure Glaucoma: Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.

Diabetes and Hypoglycemia: Latent diabetes mellitus may become manifest and diabetic patients given thiazides may require adjustment of their insulin dose.

Renal Disease: Cumulative effects of the thiazides may develop in patients with impaired renal function. In such patients, thiazides may precipitate azotemia.

Precautions

Electrolyte and Fluid Balance Status: In published studies, clinically significant hypokalemia has been consistently less common in patients who received 12.5 mg of hydrochlorothiazide than in patients who received higher doses. Nevertheless, periodic determination of serum electrolytes should be performed in patients who may be at risk for the development of hypokalemia. Patients should be observed for signs of fluid or electrolyte disturbances, i.e., hyponatremia, hypochloremic alkalosis, and hypokalemia and hypomagnesemia.

Warning signs or symptoms of fluid and electrolyte imbalance include dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting.

Hypokalemia may develop, especially with brisk diuresis when severe cirrhosis is present, during concomitant use of corticosteroid or adrenocorticotropic hormone (ACTH) or after prolonged therapy. Interference with adequate oral electrolyte intake will also contribute to hypokalemia. Hypokalemia and hypomagnesemia can provoke ventricular arrhythmias or sensitize or exaggerate the response of the heart to the toxic effects of digitalis. Hypokalemia may be avoided or treated by potassium supplementation or increased intake of potassium rich foods.

Dilutional hyponatremia is life-threatening and may occur in edematous patients in hot weather; appropriate therapy is water restriction rather than salt administration, except in rare instances when the hyponatremia is life-threatening. In actual salt depletion, appropriate replacement is the therapy of choice.

Hyperuricemia: Hyperuricemia or acute gout may be precipitated in certain patients receiving thiazide diuretics.

Impaired Hepatic Function: Thiazides should be used with caution in patients with impaired hepatic function. They can precipitate hepatic coma in patients with severe liver disease.

Parathyroid Disease: Calcium excretion is decreased by thiazides, and pathologic changes in the parathyroid glands, with hypercalcemia and hypophosphatemia, have been observed in a few patients on prolonged thiazide therapy.

Drug Interactions

When given concurrently the following drugs may interact with thiazide diuretics:

Alcohol, barbiturates, or narcotics - potentiation of orthostatic hypotension may occur.

Antidiabetic drugs - (oral agents and insulin) dosage adjustment of the antidiabetic drug may be required.

Other antihypertensive drugs - additive effect or potentiation.

Cholestyramine and colestipol resins - Cholestyramine and colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85 and 43 percent, respectively.

Corticosteroid, ACTH – intensified electrolyte depletion, particularly hypokalemia.

Pressor amines (e.g., norepinephrine) - possible decreased response to pressor amines but not sufficient to preclude their use.

Skeletal muscle relaxants, nondepolarizing (e.g., tubocurarine) - possible increased responsiveness to the muscle relaxant.

Lithium - generally should not be given with diuretics. Diuretic agents reduce the renal clearance of lithium and greatly increase the risk of lithium toxicity. Refer to the package insert for lithium preparations before use of such preparations with hydrochlorothiazide.

Non-steroidal anti-inflammatory drugs - In some patients, the administration of a non-steroidal anti-inflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing and thiazide diuretics. When hydrochlorothiazide and non-steroidal anti-inflammatory agents are used concomitantly, the patients should be observed closely to determine if the desired effect of the diuretic is obtained.

Drug/Laboratory Test Interactions

Thiazides should be discontinued before carrying out tests for parathyroid function (see PRECAUTIONS, General).

Carcinogenesis, Mutagenesis, Impairment of Fertility

Two-year feeding studies in mice and rats conducted under the auspices of the National Toxicology Program (NTP) uncovered no evidence of a carcinogenic potential of hydrochlorothiazide in female mice (at doses of up to approximately 600 mg/kg/day) or in male and female rats (at doses of approximately 100 mg/kg/day). The NTP, however, found equivocal evidence for hepatocarcinogenicity in male mice. Hydrochlorothiazide was not genotoxic in vitro in the Ames mutagenicity assay of Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 and in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations, or in vivo in assays using mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene. Positive test results were obtained only in the in vitro CHO Sister Chromatid Exchange (clastogenicity) and in the Mouse Lymphoma Cell (mutagenicity) assays, using concentrations of hydrochlorothiazide from 43 to 1300 mcg/mL, and in the Aspergillus nidulans non-disjunction assay at an unspecified concentration.

Hydrochlorothiazide had no adverse effects on the fertility of mice and rats of either sex in studies wherein these species were exposed, via their diet, to doses of up to 100 and 4 mg/kg, respectively, prior to conception and throughout gestation.

Pregnancy

Teratogenic Effects

Pregnancy Category B: Studies in which hydrochlorothiazide was orally administered to pregnant mice and rats during their respective periods of major organogenesis at doses up to 3000 and 1000 mg hydrochlorothiazide/kg, respectively, provided no evidence of harm to the fetus.

There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nonteratogenic Effects

Thiazides cross the placental barrier and appear in cord blood. There is a risk of fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults.

Nursing Mothers

Thiazides are excreted in breast milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue hydrochlorothiazide, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Elderly Use

A greater blood pressure reduction and an increase in side effects may be observed in the elderly (i.e., >65 years) with hydrochlorothiazide. Starting treatment with the lowest available dose of hydrochlorothiazide (12.5 mg) is therefore recommended. If further titration is required, 12.5 mg increments should be utilized.

Adverse Reactions

The adverse reactions associated with hydrochlorothiazide have been shown to be dose related. In controlled clinical trials, the adverse events reported with doses of 12.5 mg hydrochlorothiazide once daily were comparable to placebo. The following adverse reactions have been reported for doses of hydrochlorothiazide 25 mg and greater and, within each category, are listed in the order of decreasing severity.

Body as a whole: Weakness.

Cardiovascular: Hypotension including orthostatic hypotension (may be aggravated by alcohol, barbiturates, narcotics or antihypertensive drugs).

Digestive: Pancreatitis, jaundice (intrahepatic cholestatic jaundice), diarrhea, vomiting, sialadenitis, cramping, constipation, gastric irritation, nausea, anorexia.

Hematologic: Aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia.

Hypersensitivity: Anaphylactic reactions, necrotizing angiitis (vasculitis and cutaneous vasculitis), respiratory distress including pneumonitis and pulmonary edema, photosensitivity, fever, urticaria, rash, purpura.

Metabolic: Electrolyte imbalance (see PRECAUTIONS), hyperglycemia, glycosuria, hyperuricemia.

Musculoskeletal: Muscle Spasm.

Nervous System/Psychiatric: Vertigo, paresthesia, dizziness, headache, restlessness.

Renal: Renal failure, renal dysfunction, interstitial nephritis (see WARNINGS).

Skin: Erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis, alopecia.

Special Senses: Transient blurred vision, xanthopsia.

Urogenital: Impotence.

Whenever adverse reactions are moderate or severe, thiazide dosage should be reduced or therapy withdrawn.

Overdosage

The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias.

In the event of overdosage, symptomatic and supportive measures should be employed. Emesis should be induced or gastric lavage performed. Correct dehydration, electrolyte imbalance, hepatic coma and hypotension by established procedures. If required, give oxygen or artificial respiration for respiratory impairment. The degree to which hydrochlorothiazide is removed by hemodialysis has not been established.

The oral LD50 of hydrochlorothiazide is greater than 10 g/kg in the mouse and rat.

Hydrochlorothiazide Capsules Dosage and Administration

For Control of Hypertension: The adult initial dose of Hydrochlorothiazide Capsules is one capsule given once daily whether given alone or in combination with other antihypertensives. Total daily doses greater than 50 mg are not recommended.

How is Hydrochlorothiazide Capsules Supplied

Hydrochlorothiazide Capsules, 12.5 mg are #4 Teal Opaque/Teal Opaque capsules imprinted with Logo “LANNETT” on the cap and “1635” on the body.

They are packaged in bottles of 100 (NDC 0527-1635-01), 500 (NDC 0527-1635-05) and 1000 (NDC 0527-1635-10).

PHARMACIST: Dispense in a tight, light-resistant container as defined in the USP.

Keep out of reach of children.

Store at room temperature, 20°-25°C (68°-77°F). [See USP controlled room temperature.] Protect from light, moisture, freezing, -20°C (-4°F). Keep container tightly closed.

Rx Only

Manufactured by:

LANNETT COMPANY, INC.

Philadelphia, PA 19136

Made in the USA

Revised: 04/11

10-578

PRINCIPAL DISPLAY PANEL — Container Label

NDC 0527-1635-01

Lannett

HYDROCHLOROTHIAZIDE

CAPSULES

12.5 mg

Rx Only

100 CAPSULES

HYDROCHLOROTHIAZIDE  hydrochlorothiazide  capsule

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0527-1635 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength HYDROCHLOROTHIAZIDE (HYDROCHLOROTHIAZIDE) HYDROCHLOROTHIAZIDE 12.5 mg

Inactive Ingredients Ingredient Name Strength LACTOSE MONOHYDRATE   STARCH, CORN   SODIUM STARCH GLYCOLATE TYPE A POTATO   MAGNESIUM STEARATE   SILICON DIOXIDE   D&C RED NO. 28   D&C YELLOW NO. 10   FD&C BLUE NO. 1   GELATIN   TITANIUM DIOXIDE   SHELLAC   ALCOHOL   FERROSOFERRIC OXIDE   BUTYL ALCOHOL   PROPYLENE GLYCOL   METHYL ALCOHOL   FD&C BLUE NO. 2   FD&C RED NO. 40   ALUMINUM OXIDE

Product Characteristics Color GREEN (Teal Opaque) Score no score Shape CAPSULE Size 14mm Flavor Imprint Code LANNETT;1635 Contains

Packaging # NDC Package Description Multilevel Packaging 1 0527-1635-01 100 CAPSULE In 1 BOTTLE None 2 0527-1635-05 500 CAPSULE In 1 BOTTLE None 3 0527-1635-10 1000 CAPSULE In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA091662	01/27/2012

Labeler - Lannett Company, Inc. (002277481)

Establishment
Name	Address	ID/FEI	Operations
Lannett Company, Inc.		002277481	MANUFACTURE

Establishment
Name	Address	ID/FEI	Operations
Lannett Company, Inc.		829757603	ANALYSIS, LABEL, MANUFACTURE, PACK

Revised: 02/2012Lannett Company, Inc.

Junik

Junik may be available in the countries listed below.

Ingredient matches for Junik

Beclometasone

Beclometasone 17α,21-dipropionate (a derivative of Beclometasone) is reported as an ingredient of Junik in the following countries:

• Germany

International Drug Name Search

Alti-Mpa

Generic Name: progestin (Oral route, Parenteral route, Vaginal route)

Commonly used brand name(s)

In the U.S.

• Aygestin


• Camila


• Crinone


• Errin


• First-Progesterone VGS


• Jolivette


• Megace


• Megace ES


• Next Choice


• Ovrette


• Plan B


• Prochieve


• Prometrium

In Canada

• Alti-Mpa


• Megace Os

Available Dosage Forms:

• Tablet


• Suspension


• Capsule, Liquid Filled


• Gel/Jelly


• Cream


• Kit


• Suppository

Uses For Alti-Mpa

Progestins are hormones. They are used by both men and women for different purposes.

Progestins are prescribed for several reasons:

• To properly regulate the menstrual cycle and treat unusual stopping of the menstrual periods (amenorrhea). Progestins work by causing changes in the uterus. After the amount of progestins in the blood drops, the lining of the uterus begins to come off and vaginal bleeding occurs (menstrual period). Progestins help other hormones start and stop the menstrual cycle. .


• To help a pregnancy occur during egg donor or infertility procedures in women who do not produce enough progesterone. Also, progesterone is given to help maintain a pregnancy when not enough of it is made by the body.


• To prevent estrogen from thickening the lining of the uterus (endometrial hyperplasia) in women around menopause who are being treated with estrogen for ovarian hormone therapy (OHT). OHT is also called hormone replacement therapy (HRT) and estrogen replacement therapy (ERT).


• To treat pain that is related to endometriosis, a condition where the endometrial tissue which lines the uterus becomes displaced in other female organs.


• To treat a condition called endometriosis, to help prevent endometrial hyperplasia, or to treat unusual and heavy bleeding of the uterus (dysfunctional uterine bleeding) by starting or stopping the menstrual cycle.


• To help treat cancer of the breast, kidney, or uterus. Progestins help change the cancer cell's ability to react to other hormones and proteins that cause tumor growth. In this way, progestins can stop the growth of a tumor.


• To test the body's production of certain hormones such as estrogen.


• To treat loss of appetite and severe weight or muscle loss in patients with acquired immunodeficiency syndrome (AIDS) or cancer by causing certain proteins to be produced that cause increased appetite and weight gain.

Progestins may also be used for other conditions as determined by your doctor.

Depending on how much and which progestin you use or take, a progestin can have different effects. For instance, high doses of progesterone are necessary for some women to continue a pregnancy while other progestins in low doses can prevent a pregnancy from occurring. Other effects include causing weight gain, increasing body temperature, developing the milk-producing glands for breast-feeding, and relaxing the uterus to maintain a pregnancy.

Progestins can help other hormones work properly. Progestins may help to prevent anemia (low iron in blood), too much menstrual blood loss, and cancer of the uterus.

Progestins are 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, progestins are used in certain patients with the following medical conditions:

• Carcinoma of the prostate


• Corpus luteum insufficiency


• Hot flashes


• Polycystic ovary syndrome


• Precocious puberty

Before Using Alti-Mpa

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to medicines in this group 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

Although there is no specific information comparing use of progestins in children or teenagers with use in other age groups, this medicine is not expected to cause different side effects or problems in children or teenagers than it does in adults.

Geriatric

This medicine has been tested and has not been shown to cause different side effects or problems in older people than it does in younger adults.

Pregnancy

Progesterone, a natural hormone that the body makes during pregnancy, has not caused problems. In fact, it is sometimes used in women to treat a certain type of infertility and to aid in egg donor or infertility procedures.

Other progestins have not been studied in pregnant women. Be sure to tell your doctor if you become pregnant while using any of the progestins. It is best to use some kind of birth control method while you are receiving progestins in high doses. High doses of progestins are not recommended for use during pregnancy since there have been some reports that they may cause birth defects in the genitals (sex organs) of a male fetus. Also, some of these progestins may cause male-like changes in a female fetus and female-like changes in a male fetus, but these problems usually can be reversed. Low doses of progestins, such as those doses used for contraception, have not caused major problems when used accidentally during pregnancy.

Breast Feeding

Although progestins pass into the breast milk, they have not been shown to cause problems in nursing babies. However, progestins may change the quality or amount (increase or decrease) of the mother's breast milk. It may be necessary for you to take another medicine or to stop breast-feeding during treatment. Be sure you have discussed the risks and benefits of the medicine with your doctor.

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 any of these medicines, 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 medicines in this class with any of the following medicines is not recommended. Your doctor may decide not to treat you with a medication in this class or change some of the other medicines you take.

• Boceprevir


• Dofetilide

Using medicines in this class with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Felbamate


• Isotretinoin


• Theophylline


• Tizanidine


• Tranexamic Acid

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 medicines in this class. Make sure you tell your doctor if you have any other medical problems, especially:

• Asthma or


• Epilepsy (or history of) or


• Heart or circulation problems or


• Kidney disease (severe) or


• Migraine headaches—Progestins may cause fluid retention which may cause these conditions to become worse.

• Bleeding problems, undiagnosed, such as blood in the urine or changes in vaginal bleeding—May make diagnosis of these problems more difficult.

• Blood clots, or history of or


• Breast cancer, or history of or


• Deep vein thrombosis (blood clot in the leg), active or history of or


• Heart attack, active or history of or


• Liver disease, including jaundice, or history of or


• Pulmonary embolism (clot in the lung), active or history of or


• Stroke , active or history of or


• Venous thromboembolism (clot in the veins), or history of—Progestins should not be used in patients with these conditions.

• Breast disease (such as breast lumps or cysts), history of—May make this condition worse for diseases that do not react in a positive way to progestins.

• Diabetes mellitus—May cause an increase in your blood sugar and a change in the amount of medicine you take for diabetes; progestins in high doses are more likely to cause this problem.

• Memory loss (dementia)—May make this condition worse.

• Vision changes—This medicine may cause changes in vision; your medicine may need to be stopped if these conditions become worse.

Proper Use of progestin

This section provides information on the proper use of a number of products that contain progestin. It may not be specific to Alti-Mpa. Please read with care.

To make the use of a progestin as safe and reliable as possible, you should understand how and when to take it and what effects may be expected. Progestins usually come with patient directions. Read them carefully before taking or using this medicine.

Take this medicine only as directed by your doctor. Do not take more of it and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects. Try to take the medicine at the same time each day to reduce the possibility of side effects and to allow it to work better.

Progestins are often given together with certain medicines. If you are using a combination of medicines, make sure that you take each one at the proper time and do not mix them. Ask your health care professional to help you plan a way to remember to take your medicines at the right times.

Dosing

The dose medicines in this class 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 these medicines. 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 medroxyprogesterone


• For oral dosage form (tablets):
  
  • For controlling unusual and heavy bleeding of the uterus (dysfunctional uterine bleeding) or treating unusual stopping of menstrual periods (amenorrhea):
    
    • Adults and teenagers—5 to 10 milligrams (mg) per day for five to ten days as directed by your doctor.
    
    
  
  
  • For preparing the uterus for the menstrual period:
    
    • Adults and teenagers—10 milligrams (mg) per day for five or ten days as directed by your doctor.
    
    
  
  
  • For preventing estrogen from thickening the lining of the uterus (endometrial hyperplasia) when taking estrogen for ovarian hormone therapy in postmenopausal women:
    
    • Adults—When taking estrogen each day on Days 1 through 25: Oral, 5 to 10 milligrams (mg) of medroxyprogesterone per day for ten to fourteen or more days each month as directed by your doctor. Or, your doctor may want you to take 2.5 or 5 mg per day without stopping. Your doctor will help decide the number of tablets that is best for you and when to take them.
    
    
  
  


• For intramuscular injection dosage form:
  
  • For treating cancer of the kidneys or uterus:
    
    • Adults and teenagers—At first, 400 to 1000 milligrams (mg) injected into a muscle as a single dose once a week. Then, your doctor may lower your dose to 400 mg or more once a month.
    
    
  
  


• For subcutaneous injection dosage form:
  
  • For treating pain related to endometriosis:
    
    • Adults and teenagers—104 milligrams (mg) injected under the skin of the anterior thigh or abdomen every three months (12 to 14 weeks) for not more than 2 years.
    
    
  
  

• For megestrol


• For oral dosage form (suspension):
  
  • For treating loss of appetite (anorexia), muscles (cachexia), or weight caused by acquired immunodeficiency syndrome (AIDS):
    
    • Adults and teenagers—800 milligrams (mg) a day for the first month. Then your doctor may want you to take 400 or 800 mg a day for three more months.
    
    
  
  


• For oral dosage form (tablets):
  
  • For treating cancer of the breast:
    
    • Adults and teenagers—160 milligrams (mg) a day as a single dose or in divided doses for two or more months.
    
    
  
  
  • For treating cancer of the uterus:
    
    • Adults and teenagers—40 to 320 milligrams (mg) a day for two or more months.
    
    
  
  
  • For treating loss of appetite (anorexia), muscles (cachexia), or weight caused by cancer:
    
    • Adults and teenagers—400 to 800 milligrams (mg) a day.
    
    
  
  

• For norethindrone


• For oral dosage form (tablets):
  
  • For controlling unusual and heavy bleeding of the uterus (dysfunctional uterine bleeding) or treating unusual stopping of menstrual periods (amenorrhea):
    
    • Adults and teenagers—2.5 to 10 milligrams (mg) a day from Day 5 through Day 25 (counting from the first day of the last menstrual cycle). Or, your doctor may want you to take the medicine only for five to ten days as directed.
    
    
  
  
  • For treating endometriosis:
    
    • Adults and teenagers—At first, 5 milligrams (mg) a day for two weeks. Then, your doctor may increase your dose slowly up to 15 mg a day for six to nine months. Let your doctor know if your menstrual period starts. Your doctor may want you to take more of the medicine or may want you to stop taking the medicine for a short period of time.
    
    
  
  

• For progesterone


• For oral dosage form (capsules):
  
  • For preventing estrogen from thickening the lining of the uterus (endometrial hyperplasia) when taking estrogen for ovarian hormone therapy in postmenopausal women:
    
    • Adults—200 milligrams (mg) per day at bedtime for 12 continuous days per 28-day cycle of estrogen treatment each month.
    
    
  
  
  • For treating unusual stopping of menstrual periods (amenorrhea):
    
    • Adults—400 milligrams (mg) per day at bedtime for ten days.
    
    
  
  


• For vaginal dosage form (gel):
  
  • For treating unusual stopping of menstrual periods (amenorrhea):
    
    • Adults and teenagers—45 milligrams (mg) (one applicatorful of 4% gel) once every other day for up to six doses. Dose may be increased to 90 mg (one applicatorful of 8% gel) once every other day for up to six doses if needed.
    
    
  
  
  • For use with infertility procedures:
    
    • Adults and teenagers—90 milligrams (mg) (one applicatorful of 8% gel) one or two times a day. If pregnancy occurs, treatment can continue for up to ten to twelve weeks.
    
    
  
  


• For injection dosage form:
  
  • For controlling unusual and heavy bleeding of the uterus (dysfunctional uterine bleeding) or treating unusual stopping of menstrual periods (amenorrhea):
    
    • Adults and teenagers—5 to 10 milligrams (mg) a day injected into a muscle for six to ten days. Or, your doctor may want you to receive 100 or 150 mg injected into a muscle as a single dose. Sometimes your doctor may want you first to take another hormone called estrogen. If your menstrual period starts, your doctor will want you to stop taking the medicine.
    
    
  
  


• For vaginal dosage form (suppositories):
  
  • For maintaining a pregnancy (at ovulation and at the beginning of pregnancy):
    
    • Adults and teenagers—25 mg to 100 milligrams (mg) (one suppository) inserted into the vagina one or two times a day beginning near the time of ovulation. Your doctor may want you to receive the medicine for up to eleven weeks.
    
    
  
  

Missed Dose

If you miss a dose of this medicine, 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.

For all progestins, except for progesterone capsules for postmenopausal women: If you miss a dose of this medicine, take the missed dose 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.

For progesterone capsules for postmenopausal women: If you miss a dose of 200 mg of progesterone capsules at bedtime, take 100 mg in the morning then go back to your regular dosing schedule. If you take 300 mg of progesterone a day and you miss your morning and evening doses, you should not take the missed dose. Return to your regular dosing schedule.

Storage

Keep out of the reach of children.

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

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using Alti-Mpa

It is very important that your doctor check your progress at regular visits. This will allow for your dosage to be adjusted and for any unwanted effects to be detected. These visits will usually be every 6 to 12 months, but some doctors require them more often.

The Prometrium® capsules contain peanut oil. If you have an allergy to peanuts, make sure your doctor knows this before you take this brand of progestin.

Progestins may cause some people to become dizzy. For oral or vaginal progesterone, dizziness or drowsiness may occur 1 to 4 hours after taking or using it. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are not alert.

Unusual or unexpected vaginal bleeding of various amounts may occur between your regular menstrual periods during the first 3 months of use. This is sometimes called spotting when slight, or breakthrough menstrual bleeding when heavier. If this should occur, continue on your regular dosing schedule. Check with your doctor:

• If unusual or unexpected vaginal bleeding continues for an unusually long time.


• If your menstrual period has not started within 45 days of your last period.

Missed menstrual periods may occur. If you suspect a pregnancy, you should stop taking this medicine immediately and call your doctor. Your doctor will let you know if you should continue taking the progestin.

If you are scheduled for any laboratory tests, tell your health care professional that you are taking a progestin. Progestins can change certain test results.

In some patients, tenderness, swelling, or bleeding of the gums may occur. Brushing and flossing your teeth carefully and regularly and massaging your gums may help prevent this. See your dentist regularly to have your teeth cleaned. Check with your medical doctor or dentist if you have any questions about how to take care of your teeth and gums, or if you notice any tenderness, swelling, or bleeding of your gums.

You will need to use a birth control method while taking progestins for noncontraceptive use if you are fertile and sexually active.

If you are using vaginal progesterone, avoid using other vaginal products for 6 hours before and for 6 hours after inserting the vaginal dose of progesterone.

Since it is possible that certain doses of progestins may cause temporary thinning of the bones by changing your hormone balance, it is important that your doctor know if you have an increased risk of osteoporosis. Some things that can increase your risk for having osteoporosis include cigarette smoking, abusing alcohol, taking or drinking large amounts of caffeine, and having a family history of osteoporosis or easily broken bones. Some medicines, such as glucocorticoids (cortisone-like medicines) or anticonvulsants (seizure medicine), can also cause thinning of the bones. However, it is thought that progestins can help protect against osteoporosis in postmenopausal women.

Alti-Mpa Side Effects

Along with their needed effects, progestins used in high doses sometimes cause some unwanted effects such as blood clots, heart attacks, and strokes, or problems of the liver and eyes. Although these effects are rare, some of them can be very serious and cause death. It is not clear if these problems are due to the progestin. They may be caused by the disease or condition for which progestins are being used.

The following side effects may be caused by blood clots. Although not all of these side effects may occur, if they do occur they need immediate medical attention.

Get emergency help immediately if any of the following side effects occur:

Rare

• Symptoms of blood clotting problems, usually severe or sudden, such as:


• headache or migraine


• loss of or change in speech, coordination, or vision


• numbness of or pain in chest, arm, or leg


• unexplained shortness of breath

Check with your doctor as soon as possible if any of the following side effects occur:

More common

• Changes in vaginal bleeding (increased amounts of menstrual bleeding occurring at regular monthly periods, lighter vaginal bleeding between menstrual periods, heavier vaginal bleeding between regular monthly periods, or stopping of menstrual periods)


• symptoms of blood sugar problems (dry mouth, frequent urination, loss of appetite, or unusual thirst)

Less common

• Mental depression


• skin rash


• unexpected or increased flow of breast milk

RareFor megestrol—During chronic treatment

• Backache


• dizziness


• filling or rounding out of the face


• irritability


• mental depression


• nausea or vomiting


• unusual decrease in sexual desire or ability in men


• unusual tiredness or weakness

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:

More common

• Abdominal pain or cramping


• bloating or swelling of ankles or feet


• blood pressure increase (mild)


• dizziness


• drowsiness (progesterone only)


• headache (mild)


• mood changes


• nervousness


• pain or irritation at place of injection site


• swelling of face, ankles, or feet


• unusual or rapid weight gain

Less common

• Acne


• breast pain or tenderness


• brown spots on exposed skin, possibly long-lasting


• hot flashes


• loss or gain of body, facial, or scalp hair


• loss of sexual desire


• trouble in sleeping

Not all of the side effects listed above have been reported for each of these medicines, but they have been reported for at least one of them. All of the progestins are similar, so any of the above side effects may occur with any of these medicines.

After you stop using this medicine, your body may need time to adjust. The length of time this takes depends on the amount of medicine you were using and how long you used it. During this period of time check with your doctor if you notice the following side effect:

For megestrol

• Dizziness


• nausea or vomiting


• unusual tiredness or weakness

• Delayed return to fertility


• stopping of menstrual periods


• unusual menstrual bleeding (continuing)

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.

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.

Aldoril 25

Generic Name: hydrochlorothiazide and methyldopa (HYE droe KLOR oh THYE a zide and METH il DOE pa)

Brand Names: Aldoril 15, Aldoril 25, Aldoril D30, Aldoril D50

What is Aldoril 25 (hydrochlorothiazide and methyldopa)?

Methyldopa lowers blood pressure by decreasing the levels of certain chemicals in your blood. This allows your blood vessels (veins and arteries) to relax (widen) and your heart to beat more slowly and easily.

Hydrochlorothiazide is a thiazide diuretic (water pill) that helps prevent your body from absorbing too much salt, which can cause fluid retention.

The combination of hydrochlorothiazide and methyldopa is used to treat high blood pressure (hypertension).

Hydrochlorothiazide and methyldopa may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Aldoril 25 (hydrochlorothiazide and methyldopa)?

You should not use this medication if you are allergic to methyldopa (Apresoline) or hydrochlorothiazide, if you are unable to urinate, or if you have liver disease (including cirrhosis or hepatitis), or a history of liver problems caused by taking methyldopa. Do not use hydrochlorothiazide and methyldopa 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.

Before using hydrochlorothiazide and methyldopa, tell your doctor if you have kidney disease (or are on dialysis), angina pectoris (chest pain), glaucoma, asthma, gout, lupus, diabetes, an allergy to sulfa drugs or penicillin, or if you have ever had a stroke.

Avoid becoming overheated or dehydrated during exercise and in hot weather. Follow your doctor's instructions about the type and amount of liquids you should drink. In some cases, drinking too much liquid can be as unsafe as not drinking enough.

There are many other drugs that can interact with hydrochlorothiazide and methyldopa. 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. Keep a list of all your medicines and show it to any healthcare provider who treats you.

Keep using this medicine as directed, even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

What should I discuss with my doctor before taking Aldoril 25 (hydrochlorothiazide and methyldopa)?

Do not use hydrochlorothiazide and methyldopa 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 are allergic to methyldopa (Apresoline) or hydrochlorothiazide, or if you have:

• 
  

  liver disease (including cirrhosis or hepatitis);

  
  


• 
  

  a history of liver problems caused by taking methyldopa; or

  
  


• 
  

  if you are unable to urinate.

  
  

To make sure you can safely take hydrochlorothiazide and methyldopa, tell your doctor if you have any of these other conditions:

• 
  

  kidney disease (or if you are on dialysis);

  
  


• 
  

  angina pectoris (chest pain);

  
  


• 
  

  glaucoma;

  
  


• 
  

  asthma;

  
  


• 
  

  gout;

  
  


• 
  

  lupus;

  
  


• 
  

  diabetes;

  
  


• 
  

  an allergy to sulfa drugs or penicillin; or

  
  


• 
  

  if you have ever had a stroke.

  
  

FDA pregnancy category C. It is not known whether hydrochlorothiazide and methyldopa will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication. Hydrochlorothiazide and methyldopa can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take Aldoril 25 (hydrochlorothiazide and methyldopa)?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Your doctor may occasionally change your dose to make sure you get the best results.

Your blood pressure will need to be checked often. Your liver function may also need to be tested. Visit your doctor regularly.

Conditions that may cause very low blood pressure include: vomiting, diarrhea, heavy sweating, heart disease, dialysis, a low salt diet, or taking diuretics (water pills). Follow your doctor's instructions about the type and amount of liquids you should drink while taking hydrochlorothiazide and methyldopa. Tell your doctor if you have a prolonged illness that causes diarrhea or vomiting.

Your blood and urine may both be tested if you have been vomiting or are dehydrated.

Hydrochlorothiazide can interfere with the results of a thyroid test. Tell any doctor who treats you that you are using a thiazide diuretic.

If you need surgery, tell the surgeon ahead of time that you are using hydrochlorothiazide and methyldopa. You may need to stop using the medicine for a short time. Keep using this medicine as directed, even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life. Store at room temperature away from moisture, heat, and light.

What happens if I miss a dose?

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 Aldoril 25 (hydrochlorothiazide and methyldopa)?

Drinking alcohol can further lower your blood pressure and may increase certain side effects of hydrochlorothiazide and methyldopa.

Avoid becoming overheated or dehydrated during exercise and in hot weather. Follow your doctor's instructions about the type and amount of liquids you should drink. In some cases, drinking too much liquid can be as unsafe as not drinking enough.

Avoid exposure to sunlight or tanning beds. Hydrochlorothiazide and methyldopa can make you sunburn more easily. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

Aldoril 25 (hydrochlorothiazide and methyldopa) 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 hydrochlorothiazide and methyldopa and call your doctor at once if you have a serious side effect such as:

• 
  

  eye pain, vision problems;

  
  


• 
  

  feeling like you might pass out;

  
  


• 
  

  chest pain, slow heart rate, feeling short of breath, even with mild exertion;

  
  


• 
  

  swelling, rapid weight gain;

  
  


• 
  

  easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;

  
  


• 
  

  pale or yellowed skin, dark colored urine, fever, confusion or weakness;

  
  


• 
  

  nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

  
  


• 
  

  severe pain in your upper stomach spreading to your back, nausea and vomiting, fast heart rate;

  
  


• 
  

  joint pain or swelling with fever, swollen glands, muscle aches, nausea, vomiting, chest pain, unusual thoughts or behavior, and/or seizure (convulsions);

  
  


• 
  

  numbness, drooping, or loss of movement in one side of your face;

  
  


• 
  

  jerky or rolling muscle movements you cannot control;

  
  


• 
  

  high blood sugar (increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, weight loss);

  
  


• 
  

  urinating less than usual or not at all;

  
  


• 
  

  fever, skin rash, bruising, severe tingling, numbness; or

  
  


• 
  

  severe skin reaction -- fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling;severe skin reaction -- fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

  
  

Less serious side effects may include:

• 
  

  stomach cramps, diarrhea, constipation;

  
  


• 
  

  depressed mood, trouble concentrating;

  
  


• 
  

  joint pain;

  
  


• 
  

  muscle pain or weakness;

  
  


• 
  

  restless feeling;

  
  


• 
  

  dizziness, drowsiness, headache;

  
  


• 
  

  soreness or black discoloration of your tongue;

  
  


• 
  

  blurred vision; or

  
  


• 
  

  impotence, or loss of interest in sex.

  
  

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 Aldoril 25 (hydrochlorothiazide and methyldopa)?

Tell your doctor about all other medicines you use, especially:

• 
  

  cholestyramine (Prevalite, Questran);

  
  


• 
  

  colestipol (Colestid);

  
  


• 
  

  digoxin (Lanoxin);

  
  


• 
  

  insulin or oral diabetes medication;

  
  


• 
  

  lithium (Eskalith, LithoBid);

  
  


• 
  

  a barbiturate such as phenobarbital (Solfoton);

  
  


• 
  

  medicines that contain iron, such as ferrous gluconate (Fergon, Ferralet, Simron), or ferrous sulfate (Chem-Sol, Feosol, Slow Fe, and others);

  
  


• 
  

  muscle relaxers or narcotic pain medicine;

  
  


• 
  

  steroids (prednisone and others);

  
  


• 
  

  other blood pressure medications;

  
  


• 
  

  a nonsteroidal anti-inflammatory drug (NSAID) such as aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn, Naprelan, Treximet), celecoxib (Celebrex), diclofenac (Arthrotec, Cambia, Cataflam, Voltaren, Flector Patch, Pennsaid, Solareze), indomethacin (Indocin), meloxicam (Mobic), and others.

  
  

This list is not complete and other drugs may interact with hydrochlorothiazide and methyldopa. 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 Aldoril 25 resources

• Aldoril 25 Side Effects (in more detail)
• Aldoril 25 Use in Pregnancy & Breastfeeding
• Drug Images
• Aldoril 25 Drug Interactions
• Aldoril 25 Support Group
• 0 Reviews for Aldoril 25 - Add your own review/rating

Compare Aldoril 25 with other medications

• High Blood Pressure

Where can I get more information?

• Your pharmacist can provide more information about hydrochlorothiazide and methyldopa.

See also: Aldoril 25 side effects (in more detail)

Neurocrine Biosciences, Inc.

Address Neurocrine Biosciences, Inc., 12790 EL Camino Real San Diego, CA 92130 Contact Details Phone: (858) 617-7600 Website: http://www.neurocrine.com/ Careers: http://www.neurocrine.com/applications...

Multihance

Generic Name: gadobenate dimeglumine (GAD oh BEN ate dye MEG loo meen)

Brand Names: Multihance

What is Multihance (gadobenate dimeglumine)?

Gadobenate dimeglumine is a contrast agent that produces magnetic effects. It is used in combination with magnetic resonance imaging (MRI) to allow blood vessels, organs, and other non-bony tissues to be seen more clearly on the MRI.

Gadobenate dimeglumine is used to help diagnose certain disorders of the brain and spine (central nervous system).

Gadobenate dimeglumine may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Multihance (gadobenate dimeglumine)?

Gadobenate dimeglumine can cause a life-threatening condition in people with advanced kidney disease. The symptoms of this condition include:

• 
  

  burning, itching, swelling, scaling, and tightening or hardening of your skin;

  
  


• 
  

  muscle weakness;

  
  


• 
  

  joint stiffness in your arms, hands, legs, or feet;

  
  


• 
  

  deep bone pain in your ribs or your hips;

  
  


• 
  

  trouble moving; or

  
  


• 
  

  skin redness or discoloration.

  
  

Before receiving this medication, tell your doctor if you have kidney disease or if you are on dialysis. You may not be able to receive gadobenate dimeglumine.

Also tell your doctor if you have diabetes, high blood pressure, liver disease (or liver transplant), a heart rhythm disorder, a personal or family history of "Long QT Syndrome," asthma or allergies, a history of seizures, a genetic bilirubin disorder (Dubin Johnson syndrome), if you are over 60 years old, if you have ever had a reaction to a contrast agent, or if you have recently had an injury, surgery, or severe infection.

Your doctor or other healthcare provider may want to watch you for a short time after your test is over. This is to make sure you do not have any unwanted side effects or delayed reactions.

What should I discuss with my healthcare provider before receiving Multihance (gadobenate dimeglumine)?

Gadobenate dimeglumine can cause a life-threatening condition in people with advanced kidney disease. The symptoms of this condition include:

• 
  

  burning, itching, swelling, scaling, and tightening or hardening of your skin;

  
  


• 
  

  muscle weakness;

  
  


• 
  

  joint stiffness in your arms, hands, legs, or feet;

  
  


• 
  

  deep bone pain in your ribs or your hips;

  
  


• 
  

  trouble moving; or

  
  


• 
  

  skin redness or discoloration.

  
  

Before receiving this medication, tell your doctor if you have kidney disease or if you are on dialysis. You may not be able to receive gadobenate dimeglumine.

To make sure you can safely receive this medication, tell your doctor if you have any of these other conditions:

• 
  

  diabetes;

  
  


• 
  

  high blood pressure;

  
  


• 
  

  liver disease (or liver transplant);

  
  


• 
  

  a heart rhythm disorder;

  
  


• 
  

  a personal or family history of "Long QT Syndrome";

  
  


• 
  

  asthma, hay fever, or a history of food or drug allergies;

  
  


• 
  

  a history of seizures;

  
  


• 
  

  a genetic bilirubin disorder called Dubin Johnson syndrome (chronic jaundice);

  
  


• 
  

  if you are over 60 years old;

  
  


• 
  

  if you have ever had any type of reaction to a contrast agent; or

  
  


• 
  

  if you have recently had an injury, surgery, or severe infection.

  
  

FDA pregnancy category C. It is not known whether gadobenate dimeglumine will harm an unborn baby. Before you receive this medication, tell your doctor if you are pregnant. It is not known whether gadobenate dimeglumine passes into breast milk or if it could harm a nursing baby. Do not breast-feed for at least 24 hours after receiving gadobenate dimeglumine. If you use a breast pump during this time, throw out any milk you collect. Do not feed it to your baby.

How should I take Multihance (gadobenate dimeglumine)?

Gadobenate dimeglumine is injected into a vein through an IV. You will receive this injection in a clinic or hospital setting during your MRI.

Tell your caregivers if you feel any burning, pain, or swelling around the IV needle when the medicine is injected.

Your doctor or other healthcare provider may want to watch you for a short time after your test is over. This is to make sure you do not have any unwanted side effects or delayed reactions.

See also: Multihance dosage (in more detail)

What happens if I miss a dose?

Since gadobenate dimeglumine is used only during your MRI, you will not be on a dosing schedule.

What happens if I overdose?

Since this medication is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

What should I avoid after receiving Multihance (gadobenate dimeglumine)?

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Multihance (gadobenate dimeglumine) side effects

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

• 
  

  urinating less than usual or not at all;

  
  


• 
  

  drowsiness, confusion, mood changes, increased thirst, loss of appetite;

  
  


• 
  

  swelling, weight gain, feeling short of breath;

  
  


• 
  

  seizure (convulsions);

  
  


• 
  

  fast, uneven heart rate; or

  
  


• 
  

  pain, burning, swelling, blistering, or skin changes where the injection was given (may occur up to several days after injection).

  
  

Less serious side effects may include:

• 
  

  headache, dizziness;

  
  


• 
  

  nausea, vomiting;

  
  


• 
  

  fever, sweating, feeling unusually hot;

  
  


• 
  

  unusual or unpleasant taste in your mouth;

  
  


• 
  

  mild skin rash; or

  
  


• 
  

  numbness, burning pain, or tingling in your hands or feet;

  
  


• 
  

  cold feeling, warmth, pain, or bruising where the medicine was injected.

  
  

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 Multihance (gadobenate dimeglumine)?

This medication can harm the kidneys in certain people, and this effect may be increased if you also use other medicines harmful to the kidneys. Many other drugs (including some over-the-counter medicines) can harm your kidneys. Tell your doctor if you are receiving chemotherapy, or using antiviral medication, pain or arthritis medicine, any injected antibiotics, or medicines to treat a bowel disorder or prevent organ transplant rejection. You may need dose adjustments or special tests if you have recently used any of these medications.

Tell your doctor about all other medicines you use, especially:

• 
  

  cisplatin (Platinol);

  
  


• 
  

  daunorubicin (Daunoxome, Cerubidine);

  
  


• 
  

  docetaxel (Docefrez, Taxotere);

  
  


• 
  

  doxorubicin (Adriamycin, Doxil);

  
  


• 
  

  epirubicin (Ellence);

  
  


• 
  

  etoposide (Etopophos, Toposar, VePesid);

  
  


• 
  

  methotrexate (Rheumatrex, Trexall);

  
  


• 
  

  paclitaxel (Taxol, Abraxane);

  
  


• 
  

  rifampin (Rifater, Rifadin, Rifamate);

  
  


• 
  

  tamoxifen (Soltamox);

  
  


• 
  

  vinblastine (Velban), vincristine (Oncovin, Vincasar), vinorelbine (Navelbine);

  
  


• 
  

  heart or blood pressure medicine such as atenolol (Tenormin, Tenoretic), carvedilol (Coreg), labetalol (Normodyne, Trandate), metoprolol (Dutoprol, Lopressor, Toprol), nadolol (Corgard), propranolol (Inderal, InnoPran), sotalol (Betapace), and others; or

  
  


• 
  

  HIV or AIDS medication such as atazanavir (Reyataz), fosamprenavir (Lexiva), indinavir (Crixivan), nelfinavir (VIracept), ritonavir (Norvir, Kaletra) or saquinavir (Invirase).

  
  

There may be other drugs that can affect gadobenate dimeglumine. 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 Multihance resources

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

• Multihance Advanced Consumer (Micromedex) - Includes Dosage Information


• Gadobenate Dimeglumine Professional Patient Advice (Wolters Kluwer)


• MultiHance Prescribing Information (FDA)

Compare Multihance with other medications

• CNS Magnetic Resonance Imaging

Where can I get more information?

• Your doctor or pharmacist can provide more information about gadobenate dimeglumine.

See also: Multihance side effects (in more detail)