Fortamet (Metformin Hydrochloride) - Side Effects and Adverse Reactions

ADVERSE REACTIONS

FORTAMET^® Clinical Studies

In the controlled clinical studies of FORTAMET^® in patients with type 2 diabetes, a total of 424 patients received FORTAMET^® therapy (up to 2500 mg/day) and 430 patients received immediate-release metformin. Adverse reactions reported in ≥5% of the FORTAMET^® or immediate-release metformin patients are listed in Table 6. These pooled results show that the most frequently reported adverse reactions in the FORTAMET^® group were infection, diarrhea, and nausea. Similar incidences of these adverse reactions were seen in the immediate-release metformin group.

Table 6 Number and Percentage of Patients With the Most Common (Incidence ≥5%)Treatment-Emergent Signs or Symptoms by Body System and Preferred Term - Pooled Phase II and III Studies

	FORTAMET® (N=424)		Immediate-Release Metformin (N=430)
Body System     Preferred Term	n	(%)	n	(%)
Body as a Whole
Accidental Injury	31	(7.3)	24	(5.6)
Headache	20	(4.7)	22	(5.1)
Infection	87	(20.5)	90	(20.9)
Digestive System
Diarrhea	71	(16.7)	51	(11.9)
Dyspepsia	18	(4.2)	22	(5.1)
Nausea	36	(8.5)	32	(7.4)
Respiratory System
Rhinitis	18	(4.2)	24	(5.6)

The most frequent adverse events thought to be related to FORTAMET^® were diarrhea, nausea, dyspepsia, flatulence, and abdominal pain. The frequency of dyspepsia was 4.2% in the FORTAMET^® group compared to 5.1% in the immediate-release group, the frequency of flatulence was 3.5% in the FORTAMET^® group compared to 3.7% in the immediate-release group, and the frequency of abdominal pain was 3.3% in the FORTAMET^® group compared to 4.4% in the immediate-release group.

In the controlled studies, 4.7% of patients treated with FORTAMET^® and 4.9% of patients treated with immediate-release metformin were discontinued due to adverse events.

Immediate-Release Metformin

Immediate-Release Metformin Phase III Clinical Studies

In a U.S. double-blind clinical study of immediate-release metformin in patients with type 2 diabetes, a total of 141 patients received immediate-release metformin therapy (up to 2550 mg per day) and 145 patients received placebo. Adverse reactions reported in greater than 5% of the immediate-release metformin patients, and that were more common in immediate-release metformin than placebo-treated patients, are listed in Table 7.

Table 7 Most Common Adverse Reactions (>5.0%) in a Placebo-Controlled Clinical Study of Immediate-Release Metformin Monotherapy*

* Reactions that were more common in immediate-release metformin than placebo-treated patients
	Immediate-Release Metformin Monotherapy (n = 141)
		Placebo (n = 145)
Adverse Reaction	% of Patients
Diarrhea	53.2	11.7
Nausea/Vomiting	25.5	8.3
Flatulence	12.1	5.5
Asthenia	9.2	5.5
Indigestion	7.1	4.1
Abdominal Discomfort	6.4	4.8
Headache	5.7	4.8

Diarrhea led to discontinuation of study medication in 6% of patients treated with immediate-release metformin. Additionally, the following adverse reactions were reported in ≥1.0 - ≤5.0% of immediate-release metformin patients and were more commonly reported with immediate-release metformin than placebo: abnormal stools, hypoglycemia, myalgia, lightheaded, dyspnea, nail disorder, rash, sweating increased, taste disorder, chest discomfort, chills, flu syndrome, flushing, palpitation.

Pediatric Patients

No pediatric clinical studies have been conducted with FORTAMET^®. In clinical trials with immediate-release metformin in pediatric patients with type 2 diabetes, the profile of adverse reactions was similar to that observed in adults.

REPORTS OF SIDE EFFECTS / ADVERSE REACTIONS RELATED TO FORTAMET

Possible Fortamet side effects / adverse reactions in 63 year old female

Reported by a individual with unspecified qualification from United States on 2007-02-08

Patient: 63 year old female

Reactions: Myalgia, Diarrhoea, Pain, Condition Aggravated, Nail Disorder, Myocardial Infarction

Adverse event resulted in: hospitalization

Suspect drug(s):
Fortamet
    Dosage: 1000 mg, unk, oral
    Administration route: Oral
    Indication: Diabetes Mellitus
    Start date: 2006-06-01
    End date: 2006-07-01

Metformin HCL
    Dosage: 750 mg, unk, oral
    Administration route: Oral
    Indication: Diabetes Mellitus
    Start date: 2006-07-01

Other drugs received by patient: Plavix; Imdur; Atenolol; Cozaar

Possible Fortamet side effects / adverse reactions in 46 year old male

Reported by a health professional (non-physician/pharmacist) from United Kingdom on 2007-02-15

Patient: 46 year old male

Reactions: Cardio-Respiratory Arrest, Overdose, Rhabdomyolysis, Compartment Syndrome, Lactic Acidosis

Adverse event resulted in: hospitalization

Suspect drug(s):
Fortamet
    Dosage: 56 g, over 4 hrs, oral
    Administration route: Oral
    Indication: Diabetes Mellitus non-Insulin-Dependent

Ramipril
    Dosage: 35 mg, over 4 hrs, oral
    Administration route: Oral
    Indication: Hypertension

Other drugs received by patient: Alcohol (Ethanol)

Possible Fortamet side effects / adverse reactions in 60 year old female

Reported by a physician from United States on 2007-04-05

Patient: 60 year old female

Reactions: Campylobacter Intestinal Infection, Dehydration, Renal Failure Acute

Adverse event resulted in: hospitalization

Suspect drug(s):
Cozaar

Diuretics

Fortamet
    Dosage: oral
    Administration route: Oral

Other drugs received by patient: Aggrenox (Acetylsalicylic Acid); Micardis (Telemisartan); Clopidogrel; Placebo