DUAVIVE (conjugated estrogens and bazedoxifene modified release tablets) Adverse Reactions

Adverse Drug Reaction Overview

See Warnings and Precautions regarding potential induction of malignant neoplasms and adverse effects similar to those of oral contraceptives.

The most common ADRs that occurred in the conjugated estrogens/bazedoxifene group were abdominal pain, muscle spasms, and vulvovaginal mycotic infection.

Clinical Trial Adverse Drug Reactions

Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.

Patient exposure

The safety of conjugated estrogens/bazedoxifene was evaluated in 4,158 postmenopausal women who participated in multiple-dose trials. Among these, 1,224 were treated with DUAVIVE, conjugated estrogens 0.45 mg/bazedoxifene 20 mg, and 1,069 received placebo. Long-term exposure to DUAVIVE over 2 years was evaluated. There were a total of 699 women exposed to DUAVIVE for at least one year and 297 women exposed to DUAVIVE for 2 years.

Adverse events reported as reasons for discontinuation of treatment

In randomized clinical trials, 7.5 % of the 1,224 women treated with DUAVIVE discontinued treatment due to an adverse event, compared with 10.0 % of the 1,069 women who received placebo. The most common adverse event leading to discontinuation as the primary reason in the four trials for up to 2 years was hot flush in 0.7% in women treated with DUAVIVE and 1.8 % of women who received placebo.

Table 1 below lists the adverse events (regardless of causality) occurring in >1% of women treated with DUAVIVE in double-blind, placebo-controlled Phase 3 studies of up to 2 years duration.

Less Common Clinical Adverse Drug Reactions
The following lists the adverse events (regardless of causality) occurring in > 0.1 % and <1% but exceeding the placebo rate that occurred in women treated with DUAVIVE in double-blind, placebo-controlled Phase 3 studies of up to 2 years duration.
Blood and lymphatic system disorders: Anaemia, Thrombocytopenia
Cardiac disorders: Angina pectoris
Ear and labyrinth disorders: Deafness, Ear discomfort, Motion sickness, Vertigo positional
Endocrine disorders: Autoimmune thyroiditis, Goitre, Hypothyroidism
Eye disorders: Diplopia, Eye disorder, Eye haemorrhage, Eye pain, Eye pruritus, Eyelid oedema
Eyelid ptosis, Photopsia, Vision blurred, Visual impairment
Gastrointestinal disorders: Anal pruritus, Colonic polyp, Gingival pain, Haematemesis, Haemorrhoids, Mouth ulceration, Odynophagia, Oral discomfort, Oral pain, Paraesthesia oral, Tooth disorder
General disorders and administration site conditions: Axillary pain, Feeling hot, Influenza like illness, Irritability, Oedema, Temperature intolerance
Hepatobiliary disorders: Biliary colic, Cholecystitis, Cholelithiasis, Hepatic pain
Immune system disorders: Allergy to chemicals, House dust allergy
Infections and infestations: Carbuncle, Cervicitis, Diverticulitis, Fungal infection, Fungal skin infection, Genital herpes, Herpes zoster, Lower respiratory tract infection, Oral herpes, Pelvic inflammatory disease, Rhinitis, Skin infection, Staphylococcal infection, Tinea pedis, Tonsillitis,
Viral upper respiratory tract infection, Vulvovaginitis trichomonal
Injury, poisoning and procedural complications: Animal bite, Foot fracture, Head injury, Joint injury, Laceration, Rib fracture, Road traffic accident, Traumatic haematoma, Wrist fracture
Investigations: Blood alkaline phosphatase increased, Blood glucose increased, Blood potassium increased, Blood thyroid stimulating hormone increased, Blood urine present, Gamma-glutamyltransferase increased, Platelet count decreased, Transaminases increased, Ultrasound uterus abnormal, Very low density lipoprotein increased, Weight decreased, White blood cell count decreased, White blood cell count increased
Metabolism and nutrition disorders: Decreased appetite, Diabetes mellitus, Hypokalaemia, Increased appetite
Musculoskeletal and connective tissue disorders: Bunion, Bursitis, Flank pain, Groin pain, Joint swelling, Musculoskeletal discomfort, Pubic pain, Synovial cyst, Tendonitis
Musculoskeletal and connective tissue disorders: Pain in extremity
Neoplasms benign, malignant and unspecified (incl cysts and polyps): Lipoma, Malignant melanoma, Melanocytic naevus, Seborrhoeic keratosis, Thyroid neoplasm
Nervous system disorders: Burning sensation, Dysgeusia, Lethargy, Somnolence
Psychiatric disorders: Abnormal dreams, Affective disorder, Depressed mood, Libido increased, Mood swings, Nightmare, Panic attack
Renal and urinary disorders: Incontinence
Reproductive system and breast disorders: Breast cyst, Breast discharge, Breast disorder, Breast swelling, Cervical polyp, Cystocele, Dysmenorrhoea, Metrorrhagia, Rectocele, Uterine polyp, Uterine spasm, Vulvovaginal burning sensation, Vulvovaginal disorder
Respiratory, thoracic and mediastinal disorders: Dyspnoea, Epistaxis, Pharyngolaryngeal pain, Pleurisy, Respiratory tract congestion, Throat irritation, Upper respiratory tract congestion
Skin and subcutaneous tissue disorders: Chloasma, Dermatitis, Eczema, Hair growth abnormal, Hair texture abnormal, Hypertrichosis, Ingrowing nail, Pain of skin, Photosensitivity reaction, Rash generalized, Rash macular, Rash pruritic, Rosacea, Skin exfoliation, Skin lesion, Skin nodule, Urticaria
Vascular disorders: Hypotension

If adverse symptoms persist, the prescription of HT should be re-considered.