Timolol Maleate by Avera McKennan Hospital TIMOLOL MALEATE tablet

Timolol Maleate by

Drug Labeling and Warnings

Timolol Maleate by is a Prescription medication manufactured, distributed, or labeled by Avera McKennan Hospital. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

Pregnancy

Teratogenic Effects

Pregnancy Category C

Teratogenicity studies with timolol in mice, rats and rabbits at doses up to 50 mg/kg/day (approximately 40 times1 the maximum recommended daily human dose) showed no evidence of fetal malformations. Although delayed fetal ossification was observed at this dose in rats, there were no adverse effects on postnatal development of offspring. Doses of 1000 mg/kg/day (approximately 830 times1 the maximum recommended daily human dose) were maternotoxic in mice and resulted in an increased number of fetal resorptions. Increased fetal resorptions were also seen in rabbits at doses of approximately 40 times1 the maximum recommended daily human dose, in this case without apparent maternotoxicity. There are no adequate and well controlled studies in pregnant women. Timolol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Timolol maleate has been detected in human milk.

Because of the potential for serious adverse reactions from timolol in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of timolol for the treatment of hypertension or migraine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

In a clinical study of timolol in patients who had survived the acute phase of a myocardial infarction, approximately 350 patients (37%) were 65 to 75 years of age. Safety and efficacy were not different between these patients and younger patients (see CLINICAL PHARMACOLOGY: Pharmacodynamics).

Other reported clinical experience has not identified differences in response between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. (See PRECAUTIONS: Impaired Hepatic or Renal Function and Dosing in the Presence of Marked Renal Failure.)

The results from 5 single- and/or multiple-dose PK studies comparing the impact of age on the PK of hydrochlorothiazide, when given in combination with other antihypertensive drugs, were consistent. They indicated a mean median increase in Cmax and AUC of 38% and 99% respectively, in elderly relative to younger subjects.

  • ADVERSE REACTIONS

    Timolol maleate tablets are usually well tolerated in properly selected patients. Most adverse effects have been mild and transient.

    In a multi-center (12 week) clinical trial comparing timolol maleate and placebo in hypertensive patients, the following adverse reactions were reported spontaneously and considered to be causally related to timolol maleate:

    Timolol Maleate
    (n=176)
    %
    Placebo
    (n=168)
    %

    BODY AS A WHOLE

      fatigue/tiredness

    3.4

    0.6

      headache

    1.7

    1.8

      chest pain

    0.6

    0

      asthenia

    0.6

    0

    CARDIOVASCULAR

      bradycardia

    9.1

    0

      arrhythmia

    1.1

    0.6

      syncope

    0.6

    0

      edema

    0.6

    1.2

    DIGESTIVE

      dyspepsia

    0.6

    0.6

      nausea

    0.6

    0

    SKIN

      pruritus

    1.1

    0

    NERVOUS SYSTEM

      dizziness

    2.3

    1.2

      vertigo

    0.6

    0

      paresthesia

    0.6

    0

    PSYCHIATRIC

      decreased libido

    0.6

    0

    RESPIRATORY

      dyspnea

    1.7

    0.6

      bronchial spasm

    0.6

    0

      rales

    0.6

    0

    SPECIAL SENSES

      eye irritation

    1.1

    0.6

      tinnitus

    0.6

    0

    These data are representative of the incidence of adverse effects that may be observed in properly selected patients treated with timolol maleate, i.e., excluding patients with bronchospastic disease, congestive heart failure or other contraindications to beta-blocker therapy.

    In patients with migraine the incidence of bradycardia was 5 percent.

    In a coronary artery disease population studied in the Norwegian multi-center trial (see CLINICAL PHARMACOLOGY), the frequency of the principal adverse reactions and the frequency with which these resulted in discontinuation of therapy in the timolol and placebo groups were:

    Adverse Reaction*Withdrawal
    Timolol
    (n=945)
    %
    Placebo
    (n=939)
    %
    Timolol
    (n=945)
    %
    Placebo
    (n=939)
    %
  • * When an adverse reaction recurred in a patient, it is listed only once.
  • Only principal reason for withdrawal in each patient is listed. These adverse reactions can also occur in patients treated for hypertension.
  • Asthenia or Fatigue

    5

    1

    <1

    <1

    Heart Rate < 40 beats/minute

    5

    <1

    4

    <1

    Cardiac Failure-Nonfatal

    8

    7

    3

    2

    Hypotension

    3

    2

    3

    1

    Pulmonary Edema-Nonfatal

    2

    <1

    <1

    <1

    Claudication

    3

    3

    1

    <1

    AV Block 2nd or 3rd Degree

    <1

    <1

    <1

    <1

    Sinoatrial Block

    <1

    <1

    <1

    <1

    Cold Hands and Feet

    8

    <1

    <1

    0

    Nausea or Digestive Disorders

    8

    6

    1

    <1

    Dizziness

    6

    4

    1

    0

    Bronchial Obstruction

    2

    <1

    1

    <1

    The following additional adverse effects have been reported in clinical experience with the drug: Body as a Whole: anaphylaxis, extremity pain, decreased exercise tolerance, weight loss, fever; Cardiovascular: cardiac arrest, cardiac failure, cerebral vascular accident, worsening of angina pectoris, worsening of arterial insufficiency, Raynaud's phenomenon, palpitations, vasodilatation; Digestive: gastrointestinal pain, hepatomegaly, vomiting, diarrhea, dyspepsia; Hematologic: nonthrombocytopenic purpura; Endocrine: hyperglycemia, hypoglycemia; Skin: rash, skin irritation, increased pigmentation, sweating, alopecia; Musculoskeletal: arthralgia; Nervous System: local weakness, increase in signs and symptoms of myasthenia gravis; Psychiatric: depression, nightmares, somnolence, insomnia, nervousness, diminished concentration, hallucinations; Respiratory: cough; Special Senses: visual disturbances, diplopia, ptosis, dry eyes; Urogenital: impotence, urination difficulties.

    There have been reports of retroperitoneal fibrosis in patients receiving timolol maleate and in patients receiving other beta-adrenergic blocking agents. A causal relationship between this condition and therapy with beta-adrenergic blocking agents has not been established.

    Potential Adverse Effects

    In addition, a variety of adverse effects not observed in clinical trials with timolol maleate, but reported with other beta-adrenergic blocking agents, should be considered potential adverse effects of timolol. Nervous System: Reversible mental depression progressing to catatonia; an acute reversible syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability, slightly clouded sensorium, and decreased performance on neuropsychometrics; Cardiovascular: Intensification of AV block (see CONTRAINDICATIONS); Digestive: Mesenteric arterial thrombosis, ischemic colitis; Hematologic: Agranulocytosis, thrombocytopenic purpura; Allergic: Erythematous rash, fever combined with aching and sore throat, laryngospasm with respiratory distress; Miscellaneous: Peyronie's disease.

    There have been reports of a syndrome comprising psoriasiform skin rash, conjunctivitis sicca, otitis, and sclerosing serositis attributed to the beta-adrenergic receptor blocking agent, practolol. This syndrome has not been reported with timolol.

    Clinical Laboratory Test Findings

    Clinically important changes in standard laboratory parameters were rarely associated with the administration of timolol. Slight increases in blood urea nitrogen, serum potassium, uric acid, and triglycerides, and slight decreases in hemoglobin, hematocrit and HDL cholesterol occurred, but were not progressive or associated with clinical manifestations. Increases in liver function tests have been reported.

  • OVERDOSAGE

    Overdosage has been reported with timolol maleate tablets. A 30 year old female ingested 650 mg of timolol maleate (maximum recommended daily dose - 60 mg) and experienced second- and third-degree heart block. She recovered without treatment but approximately 2 months later developed irregular heart beat, hypertension, dizziness, tinnitus, faintness, increased pulse rate and borderline first degree heart block.

    The oral LD50 of the drug is 1190 and 900 mg/kg in female mice and female rats, respectively.

    An in vitro hemodialysis study, using 14C timolol added to human plasma or whole blood, showed that timolol was readily dialyzed from these fluids; however, a study of patients with renal failure showed that timolol did not dialyze readily.

    The most common signs and symptoms to be expected with overdosage with a beta-adrenergic receptor blocking agent are symptomatic bradycardia, hypotension, bronchospasm, and acute cardiac failure. Therapy with timolol should be discontinued and the patient observed closely. The following additional therapeutic measures should be considered:

  • DOSAGE AND ADMINISTRATION

    Hypertension

    The usual initial dosage of timolol maleate is 10 mg twice a day, whether used alone or added to diuretic therapy. Dosage may be increased or decreased depending on heart rate and blood pressure response. The usual total maintenance dosage is 20 to 40 mg per day. Increases in dosage to a maximum of 60 mg per day divided into two doses may be necessary. There should be an interval of at least 7 days between increases in dosages.

    Timolol maleate tablets may be used with a thiazide diuretic or with other antihypertensive agents. Patients should be observed carefully during initiation of such concomitant therapy.

    Myocardial Infarction

    The recommended dosage for long-term prophylactic use in patients who have survived the acute phase of a myocardial infarction is 10 mg given twice daily (see CLINICAL PHARMACOLOGY).

    Migraine

    The usual initial dosage of timolol maleate is 10 mg twice a day. During maintenance therapy the 20 mg daily dosage may be administered as a single dose. Total daily dosage may be increased to a maximum of 30 mg, given in divided doses, or decreased to 10 mg once per day, depending on clinical response and tolerability. If a satisfactory response is not obtained after 6 to 8 weeks use of the maximum daily dosage, therapy with timolol should be discontinued.

  • HOW SUPPLIED

    Timolol Maleate Tablets, USP are available containing 5 mg, 10 mg and 20 mg of timolol maleate, USP.

    The 5 mg tablets are green, unscored, flat-faced round tablets debossed with M over 55 on one side of the tablet and blank on the other side. They are available as follows:

    NDC: 0378-0055-01
    bottles of 100 tablets

    NDC 69189-0496-1 single dose pack with 1 tablet as repackaged by Avera McKennan Hospital

    Store at 20° to 25°C (68° to 77°F). [See USP for Controlled Room Temperature.]

    Protect from light.

    Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

    Keep container tightly closed.

    Mylan Pharmaceuticals Inc.
    Morgantown, WV 26505

    REVISED AUGUST 2006

    TIM:R15

  • Principal Display Panel

    Timolol Maleate 5 mg tablets

  • INGREDIENTS AND APPEARANCE
    TIMOLOL MALEATE 
    timolol maleate tablet
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 69189-0496(NDC:0378-0055)
    Route of AdministrationORAL
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    TIMOLOL MALEATE (UNII: P8Y54F701R) (TIMOLOL ANHYDROUS - UNII:5JKY92S7BR) TIMOLOL ANHYDROUS5 mg
    Inactive Ingredients
    Ingredient NameStrength
    SILICON DIOXIDE (UNII: ETJ7Z6XBU4)  
    CROSCARMELLOSE SODIUM (UNII: M28OL1HH48)  
    MAGNESIUM STEARATE (UNII: 70097M6I30)  
    CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)  
    STARCH, CORN (UNII: O8232NY3SJ)  
    SODIUM LAURYL SULFATE (UNII: 368GB5141J)  
    FD&C BLUE NO. 2 (UNII: L06K8R7DQK)  
    D&C YELLOW NO. 10 (UNII: 35SW5USQ3G)  
    Product Characteristics
    ColorGREENScoreno score
    ShapeROUNDSize6mm
    FlavorImprint Code M;55
    Contains    
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 69189-0496-11 in 1 DOSE PACK; Type 0: Not a Combination Product01/27/2016
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA07266801/27/2016
    Labeler - Avera McKennan Hospital (068647668)
    Establishment
    NameAddressID/FEIBusiness Operations
    Avera McKennan Hospital068647668relabel(69189-0496) , repack(69189-0496)

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