Dutoprol

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

Metoprolol is a beta-blocker. Beta-blockers affect the heart and circulation (blood flow through arteries and veins).

Hydrochlorothiazide and metoprolol is a combination medicine used to treat high blood pressure (hypertension).

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

Tell your doctor about all your current medicines and any you start or stop using, especially:

• clonidine;

• digoxin;

• diltiazem, verapamil;

• epinephrine (Epi-Pen);

• lithium;

• an MAO inhibitor--isocarboxazid, linezolid, methylene blue injection, phenelzine, rasagiline, selegiline, tranylcypromine, and others; or

• an NSAID (nonsteroidal anti-inflammatory drug)--aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib, diclofenac, indomethacin, meloxicam, and others.

This list is not complete. Other drugs may interact with hydrochlorothiazide and metoprolol, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

• It is used to treat high blood pressure.

Signs and Symptoms

The most frequently observed signs expected with overdosage of a beta adrenergic blocker are bradycardia and bradyarrhythmia, hypotension, heart failure, cardiac conduction disturbances and bronchospasm.

With thiazide diuretics, acute intoxication is rare. The most prominent feature of overdose is acute loss of fluid, electrolytes and magnesium. Signs and symptoms of overdose may include hypotension, dizziness, muscle cramps, renal impairment or failure, and sedation/ impairment of consciousness. Altered laboratory findings can also occur (e.g. hypokalemia, hypomagnesaemia, hyponatremia, hypochloremia, alkalosis, increased BUN).

Management

Care should be provided at a facility that can provide appropriate supporting measures, monitoring and supervision as treatment is symptomatic and supportive and there is no specific antidote. Limited data suggest that neither metoprolol nor hydrochlorothiazide is dialyzable. If justified, gastric lavage and/or activated charcoal can be administered.

Based on the expected pharmacologic actions and recommendations for other beta adrenergic blockers and hydrochlorothiazide, the following measures should be considered when clinically warranted.

Bradycardia and conduction disturbances: Use atropine, adrenergic-stimulating drugs or pacemaker.

Hypotension, acute heart failure, and shock: Treat with suitable volume expansion, injection of glucagon (if necessary, followed by an intravenous infusion of glucagon), intravenous administration of adrenergic drugs such as dobutamine, with α1 receptor agonistic drugs added in the presence of vasodilation.

Bronchospasm: Can usually be reversed by bronchodilators.

Dutoprol is supplied as circular, biconvex, film-coated tablets engraved on one side.

Store at 25°C (77°F). Excursions permitted to 15-30°C (59‑86°F). (See USP Controlled Room Temperature.)

25/12.5mg Bottle

NDC 59212-087-30          30 tablets

Dutoprol®(metoprolol succinate extended
release/hydrochlorothiazide tablet)

25*/12.5 mg tablets

Manufactured for:
Concordia Pharmaceuticals Inc.
St. Michael, Barbados BB11005

Rx only

CONCORDIA PHARMACEUTICALS INC

*Each tablet contains 23.75 mg of metoprolol succinate
extended release equivalent to 25 mg metoprolol tartrate,
and 12.5 mg hydrochlorothiazide.

DOSAGE: See package insert for full prescribing information

WARNING: As with all medications, keep out of the reach of
children. Store at 25°C (77°F). Excursions permitted to
15-30°C (59-86°F) [see USP Controlled Room Temperature].

DUT_BL25_30

Rev. 2_12/16

50/12.5 mg Bottle

NDC 59212-095-30          30 tablets

Dutoprol®(metoprolol succinate extended
release/hydrochlorothiazide tablet)

50*/12.5 mg tablets

Manufactured for:
Concordia Pharmaceuticals Inc.
St. Michael, Barbados BB11005

Rx only

CONCORDIA PHARMACEUTICALS INC

*Each tablet contains 47.5 mg of metoprolol succinate
extended release equivalent to 50 mg metoprolol
tartrate, and 12.5 mg hydrochlorothiazide.

DOSAGE: See package insert for full prescribing information

WARNING: As with all medications, keep out of the reach of
children. Store at 25°C (77°F). Excursions permitted to
15-30°C (59-86°F) [see USP Control Room Temperature].

DUT_BL50_30

Rev. 2_12/16

100/12.5 mg Bottle

NDC 59212-097-30          30 tablets

Dutoprol®(metoprolol succinate extended
release/hydrochlorothiazide tablet)

100*/12.5 mg tablets

Manufactured for:
Concordia Pharmaceuticals Inc.
St. Michael, Barbados BB11005

Rx only

CONCORDIA PHARMACEUTICALS INC

*Each tablet contains 95 mg of metoprolol succinate
extended release equivalent to 100 mg metoprolol
tartrate, and 12.5 mg hydrochlorothiazide

DOSAGE: See package insert for full prescribing information

WARNING: As with all medications, keep out of the reach of
children. Store at 25°C (77°F). Excursions permitted to
15-30°C (59-86°F) [see USP Controlled Room Temperature].

DUT_BL100_30
Rev. 2_12/16

Applies to hydrochlorothiazide / metoprolol: oral tablet

Along with its needed effects, hydrochlorothiazide / metoprolol 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 while taking hydrochlorothiazide / metoprolol:

• Chest pain or discomfort
• convulsions
• decreased urine
• dry mouth
• increased thirst
• lightheadedness, dizziness, or fainting
• loss of appetite
• mood changes
• muscle pain or cramps
• nausea or vomiting
• numbness or tingling in the hands, feet, or lips
• slow or irregular heartbeat
• unusual tiredness or weakness

• Ankle, knee, or great toe joint pain
• decreased ability to exercise
• difficult or labored breathing
• joint stiffness or swelling
• lower back or side pain
• swelling of the face, fingers, feet, or lower legs
• tightness in the chest

Get emergency help immediately if any of the following symptoms of overdose occur while taking hydrochlorothiazide / metoprolol:

• Blurred vision
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• chemical imbalance in the blood
• cold, clammy skin
• coma
• confusion
• cough
• dilated neck veins
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• drowsiness
• extreme fatigue
• fast or pounding heartbeat or pulse
• frequent urination
• headache
• increased volume of pale, dilute urine
• irregular breathing
• irritability
• noisy breathing
• not able to pass urine
• pain or aching in the lower legs
• pain or weakness in the hands or feet
• seizures
• sweating
• trembling
• unconsciousness
• very drowsy or sleepy
• weak pulse
• weakness and heaviness of the legs
• weight gain

Some side effects of hydrochlorothiazide / metoprolol 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:

• Chills
• diarrhea
• feeling of constant movement of self or surroundings
• fever
• general feeling of discomfort or illness
• muscle aches
• nightmares
• runny nose
• sensation of spinning
• shivering
• sleepiness
• sore throat
• trouble sleeping
• unusual drowsiness, dullness, or feeling of sluggishness

• Continuing ringing or buzzing or other unexplained noise in the ears
• decreased interest in sexual intercourse
• difficulty having a bowel movement (stool)
• earache
• hearing loss
• inability to have or keep an erection
• loss in sexual ability, desire, drive, or performance
• pinpoint red or purple spots on the skin
• weight loss

Applies to hydrochlorothiazide / metoprolol: oral tablet, oral tablet extended release

General

The most common side effects were fatigue, lethargy, flu syndrome, dizziness, vertigo, drowsiness, somnolence, and headache.[Ref]

Gastrointestinal

Common (1% to 10%): Diarrhea, digestive disorder, dry mouth, nausea, vomiting, constipation

Hydrochlorothiazide:
Frequency not reported: Sialadenitis, vomiting, diarrhea, cramping, nausea, gastric irritation, constipation

Metoprolol:
Common (1% to 10%): Diarrhea, nausea, gastric pain, constipation, flatulence, heartburn
Frequency not reported: Vomiting, retroperitoneal fibrosis
Postmarketing reports: Dry mouth[Ref]

Nervous system

Common (1% to 10%): Lethargy, dizziness, drowsiness, somnolence, headache, tinnitus

Hydrochlorothiazide:
Frequency not reported: Dizziness, headache, paresthesia

Metoprolol:
Common (1% to 10%): Tiredness, dizziness
Frequency not reported: Short-term memory loss, headache
Postmarketing reports: Somnolence, paresthesia, syncope, taste disturbance[Ref]

Other

Common (1% to 10%): Fatigue, vertigo, exercise tolerance decreased, edema, earache

Hydrochlorothiazide:
Frequency not reported: Vertigo, weakness
Postmarketing reports: Fever

Metoprolol:
Frequency not reported: Fatigue
Postmarketing reports: Lactic dehydrogenase elevation, alkaline phosphatase elevation, blood triglycerides increased, high-density lipoprotein decreased, tinnitus[Ref]

Metabolic

Common (1% to 10%): Hypokalemia, gout, anorexia

Hydrochlorothiazide:
Frequency not reported: Anorexia, hyperglycemia, hyperuricemia, hypokalemia

Metoprolol:
Frequency not reported: Weight gain[Ref]

Dermatologic

Common (1% to 10%): Sweating, purpura

Hydrochlorothiazide:
Frequency not reported: Stevens-Johnson syndrome, purpura, urticaria, rash, photosensitivity
Postmarketing reports: Erythema multiforme, exfoliative dermatitis, toxic epidermal necrolysis

Metoprolol:
Uncommon (0.1% to 1%): Pruritus
Frequency not reported: Gangrene, rash, photosensitivity, worsening of psoriasis, alopecia
Postmarketing reports: Sweating[Ref]

Gangrene has been reported very rarely in patients with preexisting severe peripheral circulatory disorders who were taking metoprolol.[Ref]

Respiratory

Common (1% to 10%): Dyspnea, nasopharyngitis

Hydrochlorothiazide:
Frequency not reported: Respiratory distress, pneumonitis, pulmonary edema

Metoprolol:
Common (1% to 10%): Shortness of breath
Uncommon (0.1% to 1%): Wheezing
Frequency not reported: Rhinitis
Postmarketing reports: Dyspnea[Ref]

Cardiovascular

Common (1% to 10%): Bradycardia

Hydrochlorothiazide:
Frequency not reported: Orthostatic hypotension, necrotizing angiitis

Metoprolol:
Common (1% to 10%): Bradycardia
Frequency not reported: Cold extremities, arterial insufficiency, palpitations, congestive heart failure
Postmarketing reports: Peripheral edema, chest pain[Ref]

Ocular

Common (1% to 10%): Blurred vision

Hydrochlorothiazide:
Frequency not reported: Transient blurred vision, xanthopsia

Metoprolol:
Postmarketing reports: Blurred vision, dry eyes[Ref]

Psychiatric

Common (1% to 10%): Nightmare

Hydrochlorothiazide:
Frequency not reported: Restlessness

Metoprolol:
Common (1% to 10%): Depression
Frequency not reported: Mental confusion, nightmare, insomnia
Postmarketing reports: Confusional state, anxiety/nervousness, hallucination, libido decreased[Ref]

Genitourinary

Common (1% to 10%): Impotence

Hydrochlorothiazide:
Frequency not reported: Glycosuria

Metoprolol:
Very rare (less than 0.01%): Peyronie's disease
Postmarketing reports: Male impotence[Ref]

Musculoskeletal

Common (1% to 10%): Muscle pain

Hydrochlorothiazide:
Frequency not reported: Muscle spasm

Metoprolol:
Frequency not reported: Arthritis
Postmarketing reports: Musculoskeletal pain, arthralgia[Ref]

Immunologic

Common (1% to 10%): Flu syndrome

Hydrochlorothiazide:
Postmarketing reports: Anaphylactic reactions[Ref]

Hepatic

Frequency not reported: Liver enzymes increased, serum bilirubin increased

Hydrochlorothiazide:
Frequency not reported: Pancreatitis, intrahepatic cholestatic jaundice

Metoprolol:
Postmarketing reports: Hepatitis, jaundice, non-specific hepatic dysfunction, transaminase elevation[Ref]

Hematologic

Hydrochlorothiazide:
Frequency not reported: Aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia, hemolytic anemia[Ref]

Renal

Hydrochlorothiazide:
Postmarketing reports: Interstitial nephritis[Ref]

Some side effects of Dutoprol may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.